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Autologous hematopoietic stem cell transplantation following high dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas

  1. Frank Peinemann1,*,
  2. Lesley A Smith2,
  3. Carmen Bartel3

Editorial Group: Cochrane Gynaecological Cancer Group

Published Online: 7 AUG 2013

Assessed as up-to-date: 5 DEC 2012

DOI: 10.1002/14651858.CD008216.pub4


How to Cite

Peinemann F, Smith LA, Bartel C. Autologous hematopoietic stem cell transplantation following high dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD008216. DOI: 10.1002/14651858.CD008216.pub4.

Author Information

  1. 1

    Children's Hospital, University of Cologne, Pediatric Oncology and Hematology, Cologne, NW, Germany

  2. 2

    Oxford Brookes University, Department of Social Work & Public Health, Faculty of Health & Life Sciences, Oxford, UK

  3. 3

    Institute for Quality and Efficiency in Health Care (IQWiG), Dep. Quality of Health Care, Cologne, Germany

*Frank Peinemann, Pediatric Oncology and Hematology, Children's Hospital, University of Cologne, Kerpener Str. 62, Cologne, NW, 50937, Germany. pubmedprjournal@gmail.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 7 AUG 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Al Balushi 2009

MethodsDuration: 2000 to 2007

Study design: retrospective report of cases without control

Treatment: number of arms: 1

Follow-up time: 18, 24, and 72 months for 3 transplanted participants


ParticipantsSetting: single center in Canada

Eligibility criteria: patients with desmoplastic small round-cell tumor

Number of participants: 5 patients with desmoplastic small round-cell tumor

  • 3 transplanted patients with metastatic desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 2 patients without HSCT


Age: not specified

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): all 5 patients were treated with a total of 4 cycles of chemotherapy regimen that includes doxorubicin 270 to 375 mg/m2, ifosfamide 36000 to 58000 mg/m2, cyclophosphamide 12500 to 21000 mg/m2, and etoposide 2700 to 4350 mg/m2 total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • Stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Andres 2006

MethodsDuration: August to October 2002

Study design: retrospective report of a single cases without control

Treatment: number of arms: 1

Follow-up time: 10 months for 1 transplanted participant


ParticipantsSetting: single center in Spain

Eligibility criteria: 1 patient with desmoplastic small round-cell tumor, no metastases

Number of participants: 1 patient

  • 1 transplanted patient with desmoplastic small round-cell tumor (included in the present review)


Age: 21 years old

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): thiotepa 1200 mg/m2, carboplatin 2000 mg/m2, and cyclophosphamide 9600 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • Stem cell source: not specified ("stem cell rescue")


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Bernbeck 2007

MethodsDuration: 2001 to 2005

Study design: retrospective report of cases without control

Treatment: number of arms: 1

Follow-up time: not reported


ParticipantsSetting: single center in Germany

Eligibility criteria: high-risk soft tissue sarcomas, that means patients that are refractory to conventional therapy (incomplete response or relapse) or may have metastases

Number of participants: 9 patients

  • 2 transplanted patients with synovial sarcoma with metastases (included in the present review)
  • not included in the present review: 6 patients with rhabdomyosarcoma
  • not included in the present review: 1 patient with Ewing sarcoma


Age: 21 and 21 years old

Gender: 1 male, 1 female


InterventionsHigh-dose chemotherapy (HDCT): topotecan 3.75 mg/m2, etoposide 500 mg/m2, carboplatin 500 mg/m2, and cyclophosphamide 1000 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • Stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: the authors have no conflict of interest to disclose


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Bertuzzi 2003

MethodsDuration: 1997 to 2002

Study design: prospective study of consecutive cases without control

Treatment: number of arms: 1

Follow-up time: time to event analysis with 2 year follow-up of transplanted participants, median follow-up 35 months


ParticipantsSetting: single center in Italy

Eligibility criteria: advanced desmoplastic small round-cell tumor at various clinical stages including 4 patients with metastases

Number of participants: 10 patients

  • 10 transplanted patients with desmoplastic small round-cell tumor (included in the present review)


Age: median 29 years of age (range 15 to 60 years)

Gender: 10 males


InterventionsHigh-dose chemotherapy (HDCT): after a four-course induction phase, patients in complete or partial response received HDCT with melphalan 160 mg/m2 plus mitoxantrone 60 mg/m2 or thiotepa 600 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • Stem cells source: peripheral blood


OutcomesPrimary outcomes: overall survival and treatment-related mortality ("no toxic deaths were observed") reported as aggregate data

Secondary outcomes: progression-free survival reported as aggregate data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designLow riskProspective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Bisogno 2010

MethodsDuration: 1999 to 2008

Study design: prospective study of cases without control

Treatment: number of arms: 1

Follow-up time: time to event analysis with 3 year follow-up of transplanted participants with a median follow-up of 27 months for survivors


ParticipantsSetting: multi-center study in Italy

Eligibility criteria: desmoplastic small round-cell tumor at various clinical stages including 4 patients with metastases

Number of participants: 14 patients

  • 14 transplanted patients with desmoplastic small round-cell tumor (included in the present review)


Age: median 10.3 years of age (range 2 to 17.8 years)

Gender: 13 males, 1 female


InterventionsHigh-dose chemotherapy (HDCT): after an induction phase of nine weeks, three consecutive intensified-dose combinations were applied: thiotepa 300 mg/m2, melphalan 60 mg/m2, cyclophosphamide 4000 mg/m2, thiotepa 300 mg/m2, and melphalan 80 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as aggregate data

Secondary outcomes: progression-free survival reported as aggregate data; toxicity reported as individual data


NotesConflict of interest: "The authors have no conflict of interest to disclose."

Support: "This research was partially supported by a grant from the Fondazione Citta della Spiranza."


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designLow riskProspective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Blay 2000

MethodsDuration: 1988 to 1994

Study design: prospective study of cases without control

Treatment: number of arms: 1

Follow-up time: time to event analysis with 5 year follow-up of transplanted participants with a median follow-up of 94 months for survivors


ParticipantsSetting: single center in France

Eligibility criteria: advanced soft tissue sarcomas

Number of participants: 30 patients, 26 patients had distant metastases and the rest of 4 had a locally advanced stage

  • 24 transplanted patients analyzed in a subgroup of patients with adult-type sarcomas excluding rhabdomyosarcoma and Ewing family of tumors; this subgroup analysis compared patients who have achieved a complete response before HDCT with those who had a partial or minor response (included in the present review, 80% of all participants)
    • 22 transplanted patients with NRSTS: 5x leiomyosarcoma, 4x synovial sarcoma, 4x undifferentiated sarcoma, 3x unclassified sarcoma, 2x angiosarcoma, 2x liposarcoma, 1x fibrosarcoma, 1x hemangiopericytoma
    • not included in the present review: 1x paraganglioma, 1x Schwannosarcoma
  • not included in the present review: 5 patients with rhabdomyosarcoma
  • not included in the present review: 1 patient with extraskeletal permeative neuroectodermal tumor (PNET)


Age: median 34 years of age (range 17 to 57 years)

Gender: 17 males, 13 female


InterventionsHigh-dose chemotherapy (HDCT): the majority of patients had received induction chemotherapy, afterwards HDCT was applied that comprised etoposide 800 mg/m2, cisplatin 200 mg/m2, ifosfamide 12000 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow (N = 25) or peripheral blood (N = 5)


OutcomesPrimary outcomes: overall survival reported as aggregate data, treatment-related mortality "one sudden toxic death"

Secondary outcomes: progression-free survival and toxicity reported as aggregate data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designLow riskProspective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Bley 2004

MethodsDuration: no information on observation period available

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 7 months for 1 transplanted participant


ParticipantsSetting: single center in Germany

Eligibility criteria: liposarcoma

Number of participants: 1 patient

  • 1 transplanted patient with liposarcoma and with autologous HSCT (included in the present review)


Age: 22 years of age

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): melphalan and busulfan

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: not specified


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Boelke 2005

MethodsDuration: in 1993

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 89 months for 1 transplanted participant


ParticipantsSetting: single center in Germany

Eligibility criteria: malignant fibrous histiocytoma

Number of participants: 1 patient

  • 1 transplanted patient with recurrent malignant fibrous histiocytoma and with autologous HSCT (included in the present review)


Age: 33 years of age

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): melphalan and busulfan

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Bokemeyer 1997

MethodsDuration: no information on observation period available

Study design: retrospective report of cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: patients were presumably treated in 3 centers in Germany according to author affiliation

Eligibility criteria: histologically proven metastatic or advanced adult soft tissue sarcoma without prior treatment, age between 18 and 60 years, a Karnofsky index greater than or equal to 50%, adequate liver, kidney, and bone marrow function

Number of participants: 18 patients

  • 16 transplanted patients with NRSTS and with autologous HSCT: 5x malignant fibrous histiocytoma, 4x hemangiopericytoma, 3x synovial sarcoma, 2x leiomyosarcoma, 2x mesenchymal sarcoma (included in the present review)
  • not included in the present review: 2x malignant Schwannoma


Age: median 45 (range 25 to 57) years of age

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): doxorubicin, 75 mg/m2, ifosfamide at different dose levels 8000, 10000, 12000, 14000, or 16000 mg/m2, total dose

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as aggregate data

Secondary outcomes: progression-free survival, toxicity reported as aggregate data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Buerk 2010

MethodsDuration: not specified

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 6 weeks for 1 transplanted participant


ParticipantsSetting: single center in Germany

Eligibility criteria: angiosarcoma

Number of participants: 1 patient

  • 1 transplanted patient with epithelioid angiosarcoma of the scapula without distant metastases (included in the present review)


Age: 48 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Bui-Nguyen 2012

MethodsDuration: 2000 to 2008

Study design: randomized controlled trial: "This open, multicenter, randomized phase III study [...]". "All patients eligible for preenrollment received the same baseline treatment [...]". "[...] eligible for randomization if they had responded to chemotherapy or, for stable disease, if a complete surgical resection of all disease sites could be carried out. Patients were ineligible for randomization if they had progressed or had only stable disease with no possibility for complete resection of the primary and/or metastatic tumor". "Randomization was stratified by center using a blocked method with block size of four and was carried out centrally". "The intention to treat (ITT)-modified population included all randomly assigned patients excluding patients found to be ineligible at central histology review."

Treatment: number of arms: 2

Follow-up time: time to event analysis at 3 years with a median follow-up of 55 months for survivors


ParticipantsSetting: multicenter trial in 16 centers in France

Eligibility criteria: patients aged 18 to 65 years with histologically confirmed, inoperable locally advanced or metastatic soft tissues sarcomas; Eastern Cooperative Oncology Group performance status of 0 or 1; normal cardiac, hepatic, and renal function, adequate bone marrow reserve; patients had received no prior chemotherapy or concurrent therapy; patients for whom it was possible to perform potentially curative locoregional treatments and patients with uterine, bone, or digestive tumors were excluded.

Number of participants: 264

  • 264 patients pre-enrolled
  • 207 patients received first 4 of 6 chemotherapy courses
  • 87 patients were randomized to HDCT plus autologous HSCT (N = 41, but data from 38 analyzed in ITT) and to SDCT (N = 46, but data from 45 analyzed in ITT)
    • 69 patients with NRSTS: 16x leiomyosarcoma, 16x malignant fibrous histiocytoma, 10x others (2x undifferentiated sarcoma, 2x malignant myoepithelioma, 1x leiomyosarcoma, 1x fibrosarcoma, 1x myofibrosarcoma, 1x unclassified sarcoma, 1x desmoplastic small round cell sarcoma), 10x liposarcoma, 9x synovial sarcoma, 6x angiosarcoma, 1x clear cell sarcoma, 1x desmoplasatic round cell sarcoma (included in the present review)
    • not included in the present review: 18 patients (20%) with diagnoses other than NRSTS: 9x rhabdomyosarcoma, 2x malignant peripheral nerve sheath tumor, 1x osteosarcoma, 1x melanoma, 5x others (3x endometrial stromal sarcoma, 1x gastro-intestinal stromal tumor, 1x triton tumor)
  • 83 patients were included in modified intention to treat analysis (ITT) to compare overall survival and progression-free survival between treatment groups; histologically ineligible patients were excluded from primary group of analysis, 3 from the HDCT plus autologous HSCT group with data from 38 patients used for ITT analysis and 1 from the SDCT group with data from 45 patients used for ITT analysis
  • 62 patients received the assigned treatment and were included in the toxicity analysis


Age: range 18.5 to 65.0 years of age, median 45.8, in the HDCT arm and 18.7 to 65.0 years of age, median 43.3, in the SDCT arm

Gender: 58.5% (24 of 41) males in the HDCT arm and 50% (23 of 46) males in the CDCT arm


InterventionsAll participants received 5 times standard-dose chemotherapy: doxorubicin 60 mg/m2, ifosfamide 7500 mg/m2, dacarbazine 900 mg/m2, total doses; the sixth course was different between arm 1 and 2:

Randomized to arm 1, sixth course:

  • High-dose chemotherapy (HDCT): ifosfamide 10000 mg/m2, carboplatin, and etoposide 1200 mg/m2, total doses


  • Autologous hematopoietic stem cell transplantation (HSCT): stem cell source: peripheral blood
  • actually 22 of 41 randomized patients received HDCT followed by HSCT


Randomized to arm 2, sixth course:

  • Standard-dose chemotherapy: doxorubicin 60 mg/m2, ifosfamide 7500 mg/m2, dacarbazine 900 mg/m2, total doses
  • actually 40 of 46 randomized patients received standard-dose chemotherapy


OutcomesPrimary outcomes:

  • Overall survival reported as aggregate data; individual data were not reported


Secondary outcomes:

  • Progression-free survival reported as aggregate data; individual data were not reported
  • Toxicity reported as individual data


NotesFinancial support: Programme Hospitalier de Recherche Clinique, French Health Ministry (non-profit organization); French National Federation for Comprehensive Cancer Centers (non-profit organization).

Information about the histological type of sarcoma designated as "others" in the article were communicated by personal contact with the first author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomization was stratified by center using a blocked method with block size of four and was carried out centrally"

Allocation concealment (selection bias)Unclear riskAllocation was carried out centrally, though, masking of allocation was not described in full detail.

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome. It was denoted as an "open, multicenter, randomized phase III study".

Selective reporting (reporting bias)Low riskWe did not detect reporting of outcomes that might be selective

Prospective designLow riskRandomized controlled trial

Comparable baseline characteristicsLow riskBaseline data including pretreatment were comparable. "All patients eligible for preenrollment received the same baseline treatment".

Assignment of patients to treatment groupsLow riskRandomized controlled trial

Concurrent controlLow riskRandomized controlled trial

Loss to follow-upLow riskLoss to follow-up was described and modified intention-to-treat analysis was performed

Cole 1999

MethodsDuration: not specified

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 6 months for 1 transplanted participant


ParticipantsSetting: single center in the United States

Eligibility criteria: synovial sarcoma

Number of participants: 1 patient

  • 1 transplanted patient with synovial sarcoma (included in the present review)


Age: 26 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Cook 2012

MethodsDuration: 1999 to 2007

Study design: retrospective registry analysis of cases without control reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Treatment: number of arms: 1

Follow-up time: median of 44 months (range 4 to 89) for survivors


ParticipantsSetting: analysis of registry data from 29 centers reported to CIBMTR located in North America except for 3 patients

Eligibility criteria: desmoplastic small round cell tumor

Number of participants: 36 patients

  • 36 transplanted patients (included in the present review)


Age: median 19 years of age (range 8 to 46 years)

Gender: 29 males, 7 females


InterventionsHigh-dose chemotherapy (HDCT): the most common agents were thiotepa, etoposide, melphalan, cyclophosphamide, and carboplatin

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow (N = 2) or peripheral blood (N = 33), information missing in 1 patient


OutcomesPrimary outcomes: overall survival and treatment-related mortality reported as aggregate data

Secondary outcomes: disease-free survival reported as aggregate data


NotesFinancial support of CIBMTR:

Grants from non-profit organizations:

  • Blue Cross and Blue Shield Association
  • Children’s Leukemia Research Association
  • National Cancer Institute (NCI)
  • National Heart, Lung and Blood Institute (NHLBI)
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • Office of Naval Research


Grants from biopharmaceutical companies

  • Allos, Inc
  • Amgen, Inc.
  • Celgene Corporation
  • CellGenix, GmbH
  • Fresenius-Biotech North America, Inc.
  • Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.
  • Genzyme Corporation
  • GlaxoSmithKline
  • Kiadis Pharma
  • Millennium Pharmaceuticals, Inc.
  • Milliman USA, Inc.
  • Miltenyi Biotec, Inc.
  • Optum Healthcare Solutions, Inc.
  • Otsuka America Pharmaceutical, Inc.
  • Seattle Genetics
  • Sigma-Tau Pharmaceuticals
  • Soligenix, Inc.
  • Swedish Orphan Biovitrum AB
  • THERAKOS, Inc.
  • Wellpoint, Inc.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Doros 2008

MethodsDuration: not specified

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 0 months for 1 transplanted participant


ParticipantsSetting: single center in the United States

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 1 patient

  • 1 transplanted patient with desmoplastic small round-cell tumor (included in the present review)


Age: 14 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: not specified ("autologous stem cell rescue")


OutcomesPrimary outcomes: overall survival and treatment-reported mortality reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Engelhardt 2007

MethodsDuration: 1992 to 2003

Study design: retrospective report of a consecutive series of cases without controls

Treatment: number of arms: 1

Follow-up time: not specified for individual participants


ParticipantsSetting: an international multicenter study, the number of centers and the name of participating countries were not specified and presumably included Germany and the United States

Eligibility criteria: high-risk Ewing sarcoma and soft tissue sarcomas, 18 years or older, tumor diameter 5 cm or more, extensive local or distant recurrence and/or metastatic disease, histologically moderately differentiated or undifferentiated tumors

Number of participants: 35 patients

  • 23 transplanted patients with NRSTS including anaplastic soft tissue sarcoma, angiosarcoma, fibrosarcoma, leiomyosarcoma, liposarcoma, malignant fibrous histiocytoma, malignant hemangioperiocytoma, synovial sarcoma (included in the present review)
  • not included in the present review: 8 patients with Ewing sarcoma
  • not included in the present review: 3 patients with rhabdomyosarcoma
  • not included in the present review: 1 patient with Schwannoma


Age: range 21 to 56 years of age of 23 patients with NRSTS

Gender: 12 males and 11 females of 23 patients with NRSTS


InterventionsHigh-dose chemotherapy (HDCT): various regimens for individual patients

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival and treatment-related mortality reported as individual data


NotesThe reported aggregate data were not considered because the proportion of participants with NRSTS was 67% (23 of 35). A proportion of at least 80% is required for extracting aggregate data.

Financial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Etienne-Mastroianni 2002

MethodsDuration: 1970 to 1999

Study design: retrospective report of cases without controls

Treatment: number of arms: 1

Follow-up time: 3 to 144 months (mean 42)


ParticipantsSetting: single center in France

Eligibility criteria: primary sarcoma of the lung, metastatic pulmonary sarcomas, as well as mediastinal, thoracic wall, pleural, and cardiac primary sarcomas were excluded; 15 years of age or older

Number of participants: 12 patients

  • 1 transplanted patient with leiomyosarcoma (included in the present review)
  • not included in the present review: 11 patients without transplantation


Age: 50 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: not reported individually


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Fang 2008

MethodsDuration: in 2006

Study design: retrospective report of cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the United States

Eligibility criteria: high-risk solid tumor of childhood

Number of participants: 2 patients

  • 1 transplanted patient with desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 1 patient with desmoplastic small round-cell tumor but no autologous HSCT


Age: 23 years of age

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: not reported individually


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Farruggia 2008

MethodsDuration: not specified

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 36 months


ParticipantsSetting: single center in Italy

Eligibility criteria: synovial sarcoma

Number of participants: 1 patient

  • 1 transplanted patient with synovial sarcoma (included in the present review)


Age: 10 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): carboplatin 500 mg/m2, epirubicine 150 mg/m2, vincristine 1.5 mg/m2 / ifosfamide 3000 mg/m2, vincristine 1.5 mg/m2, etoposide 150 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Fetscher 1996

MethodsDuration: not specified

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 1 month


ParticipantsSetting: single center in Germany

Eligibility criteria: nuchal leiomyosarcoma

Number of participants: 1 patient

  • 1 transplanted patient with leiomyosarcoma (included in the present review)


Age: 53 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Fetscher 1997

MethodsDuration: in 1994

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 36 months


ParticipantsSetting: single center in Germany

Eligibility criteria: gastric leiomyosarcoma

Number of participants: 1 patient

  • 1 transplanted patient with metastatic leiomyosarcoma (included in the present review)


Age: 23 years of age

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): etoposide 1500 mg/m2, ifosfamide 12000 mg/m2, carboplatin 1500 mg/m2, epirubicine 150 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Fraser 2006

MethodsDuration: 1995 to 2004

Study design: prospective series of cases without control

Treatment: number of arms: 1

Follow-up time: not specified for individual data


ParticipantsSetting: single center in the United States

Eligibility criteria: patients with a range of high-risk solid and brain tumors who had achieved a complete or partial response with non-progessive disease; patients had high-risk tumors that were either metastatic at diagnosis or had relapsed following therapy; adequate organ function was documented

Number of participants: 36 patients

  • 4 transplanted patients with desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 32 patients with other solid tumors such as 16x Ewing's sarcoma, 3x rhabdomyosarcoma, 2x Wilm's tumor, 2x ovarian tumor, 2x medulloblastoma, 1x hepatoblastoma, 1x retinoblastoma, 1x osteosarcoma, 1x glioblastoma multiforme, 1x ependymoma, 1x chordoma, 1 patient with cerebral rhabdoid tumor


Age: 8, 10, 14, 20 years of age

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): busulfan 12 mg/kg, melphalan 100 mg/m2, thiotepa 500 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow or peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: "This work was supported in part by a grant from the Children’s Cancer Research Fund." (national nonprofit organization)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Garrido 1998

MethodsDuration: 1991 to 1995

Study design: retrospective report of 2 cases without control

Treatment: number of arms: 1

Follow-up time: not specified for individual data


ParticipantsSetting: single center in the United States

Eligibility criteria: neuroleptic malignant syndrome after transplantation

Number of participants: 2 patients

  • 1 transplanted patient with metastatic liposarcoma (included in the present review)
  • not included in the present review: 1 transplanted patient with breast carcinoma


Age: 45 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): busulfan 12 mg/kg total dose, melphalan 100 mg/m2 total dose, thiotepa 500 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: not specified


OutcomesPrimary outcomes: not reported

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Graham 1997

MethodsDuration: 1991 to 1995

Study design: prospective report of a cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the United States

Eligibility criteria: recurrent and high-risk pediatric brain tumors after transplantation

Number of participants: 49 patients

  • 1 transplanted patient with fibrosarcoma (included in the present review)
  • not included in the present: 48 patients with diagnoses other than NRSTS: 19x medulloblastoma, 12x glial tumors, 7x pineoblastoma, 5x ependymoma, 3x Ewing family of tumors, 2x germ cell tumor


Age: not specified

Gender: not specified


InterventionsAutologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival

Secondary outcomes: toxicity


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Hara 2010

MethodsDuration: 2003 to 2009

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 67 months


ParticipantsSetting: single center in Japan

Eligibility criteria: angiosarcoma

Number of participants: 1 patient

  • 1 transplanted patient with splenic angiosarcoma (included in the present review)


Age: 48 years of age

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): ifosfamide 9000 mg/m2, etoposide 900 mg/m2, and carboplatin
1200 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Hawkins 2002

MethodsDuration: 1996 to 1998

Study design: prospective report of cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: 3 centers in the United States

Eligibility criteria: children and adolescents with metastatic sarcomas

Number of participants: 23 patients

  • 4 transplanted patients with NRSTS (included in the present review): 2x desmoplastic small round-cell tumor, 1x leiomyosarcoma, 1x fibromyxoid sarcoma
  • not included in the present: 17 patients with diagnoses other than NRSTS: 9x Ewing family of tumors, 6x rhabdomyosarcoma, 2x undifferentiated sarcoma, 1x anaplastic Wilms tumor, 1x malignant peripheral nerve sheath tumor


Age: 5 to 19 years of age

Gender: 5 male, 1 female


InterventionsHigh-dose chemotherapy (HDCT): vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Hoogerbrugge 1997

MethodsDuration: 2003 to 2009

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 8 months


ParticipantsSetting: single center in the Netherlands

Eligibility criteria: fibrosarcoma

Number of participants: 1 patient

  • 1 transplanted patient with disseminated fibrosarcoma (included in the present review)


Age: 1 year of age

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): etoposide 1500 mg/m2, carboplatin 1500 mg/m2 and melphalan 140 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: Amgen, Inc. (biopharmaceutical company) and Roche Inc. (pharmaceutical company) were acknowledged for their support of the study


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Houet 2010

MethodsDuration: not specified

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: more than 10 years


ParticipantsSetting: single center in Germany

Eligibility criteria: desmoplastic small round-cell tumour

Number of participants: 1 patient

  • 1 transplanted patient with advanced intra-abdominal desmoplastic small round-cell tumour and lymph node involvement (included in the present review)


Age: 31 years of age

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data


NotesFinancial support: grants from the Deutsche Krebshilfe (nonprofit organization)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Jordan 2010

MethodsDuration: 2004 to 2006

Study design: prospective series of cases without control

Treatment: number of arms: 1

Follow-up time: 3 to 36 months


ParticipantsSetting: single center in Germany

Eligibility criteria: histologically confirmed metastatic sarcoma or germ cell cancer, refractory to standard chemotherapy, no prior high-dose chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status of at least two and adequate hematologic, hepatic, and renal functions; exclusion criteria: newly diagnosed venous thrombosis, significant cardiovascular disease or surgery within 21 days; presence of cerebral metastases was not an exclusion criterion

Number of participants: 16 patients

  • 7 transplanted patients: 2x epitheloid sarcoma, 1x synoviaI sarcoma, 1x spindle cell sarcoma, 1x leiomyosarcoma, 1x angiosarcoma, 1x hemangiopericytoma (included in the present review)
  • not included in the present review: 5 transplanted patients: 3x osteosarcoma, 2x chondrosarcoma, 1x undifferentiated sarcoma
  • not included in the present review: 3 transplanted patients: germ cell tumor (non-seminoma)


Age: range 25 to 58 years of age

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): ifosfamide 9000 mg/m2, etoposide 900 mg/m2, carboplatin 900 mg/m2, and bevacizumab 7.5 to 10.0 mg/kg, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data


NotesFinancial support: Two authors have received compensation as a member of the scientific advisory board of Roche AG (pharmaceutical company). The remaining authors declared that they have no conflict of interest.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Kasper 2007a

MethodsDuration: 1998 to 2007

Study design: retrospective series of cases without control

Treatment: number of arms: 1

Follow-up time: 0 to 54 months (for each included case reported: 0, 2, 4, 4, 6, 11, 14, 16, 19, 20, 20, 21, 26, 54 months)


ParticipantsSetting: single center in Germany

Eligibility criteria: patients with bone and soft tissue sarcomas receiving high-dose chemotherapy and autologous stem cell support

Number of participants: 38 patients

  • 11 transplanted patients: 5x synoviaI sarcoma, 3x leiomyosarcoma, 2x liposarcoma 1x malignant fibrous histiocytoma (included in the present review)
  • not included in the present review: 20 transplanted patients: 10x Ewing family of tumors, 6x osteosarcoma, 1x chondrosarcoma, 3x not otherwise specified sarcoma
  • not included in the present review: 7 transplanted patients: 4x malignant peripheral nerve sheath tumors, 2x rhabdomyosarcomas, 1x meningosarcoma


Age: range 23 to 65 years of age

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): 23 patients: ifosfamide 12000 mg/m2, carboplatin 1200 mg/m2, and etoposide
1200 mg/m2, total doses; 7 patients: melphalan 420 mg/m2, busulfan 1800 mg/m2, total doses; 4 patients: melphalan 180 mg/m2 and etoposide 3000 mg/m2, total doses; 2 patients: melphalan 200 mg/m2; 2 patients: carboplatin 600 mg/m2, etoposide 600 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Kasper 2010

MethodsDuration: 2003 to 2008

Study design: prospective nonrandomized controlled clinical trial

Treatment: number of arms: 2

Follow-up time: follow up was not reported; overall survival was assessed from the time of study inclusion and ranged from 0 to 34 months


ParticipantsSetting: single center in Germany

Eligibility criteria: primary or recurrent metastatic soft tissues sarcoma; no patients with unresectable disease were included; normal creatinine, normal cardiac function and normal bilirubin levels were required before high-dose chemotherapy

Number of participants: 34 patients

  • 9 patients had partial response to induction chemotherapy and received HDCT and autologous HSCT:
    • 4 patients had NRSTS: 2x malignant fibrous histiocytoma, 1x leiomyosarcoma, 1x synoviaI sarcoma (included in the present review)
    • not included in the present review: 5 patients had other diagnosis (56%): 3x not otherwise specified tumor, 1x primitive neuroectodermal tumor, 1x rhabdomyosarcoma
  • 25 patients received SDCT:
    • 16 patients had NRSTS
    • 9 patients with other tumors than NRSTS including including not otherwise specified tumor (36%); 1 of the 9 patients had partial response to induction chemotherapy but refused HDCT and autologous HSCT.


Age: not specified

Gender: not specified


InterventionsArm 1:

  • High-dose chemotherapy (HDCT): ifosfamide 12000 mg/m2, carboplatin 1200 mg/m2 and etoposide 1200 mg/m2, total doses


  • Autologous hematopoietic stem cell transplantation (HSCT): stem cell source: peripheral blood


Arm 2:

  • Standard-dose chemotherapy: doxorubicin 75 mg/m2 and ifosfamide 6000 mg/m2, total doses


OutcomesPrimary outcomes:

  • Overall survival: aggregate data included less than 80% NRSTS patient data; individual data reported


Secondary outcomes:

  • Progression-free survival: aggregate data included less than 80% NRSTS patient dataAdverse events reported as individual data


NotesThe authors declared that they have no conflict of interest.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskComparative trial but only individual data were relevant

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Kozuka 2002

MethodsDuration: 1999 to 2000

Study design: retrospective report of 2 cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in Japan

Eligibility criteria: recurrent soft tissues sarcoma

Number of participants: 2 patients

  • 2 transplanted patients: 1x malignant fibrous histiocytoma, 1x malignant hemangiopericytoma (included in the present review)


Age: 21 and 37 years of age

Gender: 2 males


InterventionsHigh-dose chemotherapy (HDCT): ifosfamide 15000 mg/m2, carboplatin 1200 mg/m2, and etoposide 1500 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Kretschmar 1996

MethodsDuration: not specified

Study design: retrospective report of 3 cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the United States

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 3 patients

  • 1 transplanted patients: desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 2x desmoplastic small round-cell tumor not transplanted


Age: 13 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT)

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Krskova 2007

MethodsDuration: in 1998

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the Czech Republic

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 1 patients

  • 1 transplanted patients: synovial sarcoma (included in the present review)


Age: 9 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT)

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: not specified


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Kurre 2000

MethodsDuration: 1994 to 1998

Study design: retrospective report of 3 cases without control

Treatment: number of arms: 1

Follow-up time: 26 and 42 months after diagnosis


ParticipantsSetting: single center in the United States

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 3 patients

  • 2 transplanted patients: 2x desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 1x desmoplastic small round-cell tumor, no transplantation


Age: 5 and 2.5 years of age

Gender: 1 male and 1 female


InterventionsHigh-dose chemotherapy (HDCT): doxorubicin 75 mg/m2, cyclophosphamide 1800 mg/m2, ifosfamide 9000 mg/m2, and etoposide 500 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Kushner 1996

MethodsDuration: not specified

Study design: prospective series of cases and controls

Treatment: number of arms: 2

Follow-up time: 13 to 34 months


ParticipantsSetting: single center in the United States

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 12 patients

  • 4 transplanted patients with desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 8 patients with desmoplastic small round-cell tumor that were not transplanted


Age: 10, 11, 11, and 14 years of age


InterventionsArm 1:

Chemotherapy: cyclophosphamide 4200 mg/m2, doxorubicin 75 mg/m2, vincristine 2000 mg/m2, ifosfamide 9000 mg/m2, and etoposide 500 mg/m2, total doses

Arm 2:

Additional high-dose chemotherapy (HDCT): thiotepa 900 mg/m2 and carboplatin 1500 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT):

  • stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskControls but only individual data relevant

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Kushner 2001

MethodsDuration: not specified

Study design: preliminary results of a prospective series of cases

Treatment: number of arms: 1

Follow-up time: 2 years


ParticipantsSetting: single center in the United States

Eligibility criteria: diagnosis of a cancer that had 25% cure rate with conventional therapies; adequate function of kidneys, heart, and liver

Number of participants: 21 patients

  • 1 transplanted patients with desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 20 transplanted patients with diagnoses other than NRSTS: 11x neuroblastoma, 3x Ewing family of tumors, 3x medulloblastoma, 1x glioblastoma multiforme, 1x astrocytoma, 1x ovarian teratoma


Age: 29 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): topotecan 10 mg/m2, thiotepa 900 mg/m2, carboplatin 1500 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: This work was supported in part by grants from the National Cancer Institute (non-profit organization), the Robert Steel Foundation (non-profit organization), the Katie Find A Cure Fund (non-profit organization), and the Justin Zahn Fund (non-profit organization).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Kushner 2008

MethodsDuration: not specified

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 26 months


ParticipantsSetting: single center in the United States

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 1 patient

  • 1 transplanted patient with desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 1x desmoplastic small round-cell tumor, no transplantation


Age: 18 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): whole abdominal-pelvic radiation therapy 3000 Gy and irinotecan 250 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: Supported in part by grants from the National Cancer Institute (non-profit organization), Food and Drug Administration (non-profit organization), Hope St Kids (non-profit organization), Katie Find A Cure Fund (non-profit organization), and Robert Steel Foundation (non-profit organization).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Lafay-Cousin 2000

MethodsDuration: 1986 to 1998

Study design: prospective report of 18 cases without control

Treatment: number of arms: 1

Follow-up time: 8 to 31 months (for each included case 8, 13, 16, 31 months reported)


ParticipantsSetting: 4-center study in France

Eligibility criteria: recurrent mesenchymal tumors

Number of participants: 18 patients

  • 2 transplanted patients: 2x desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 14x transplanted patients with rhabdomyosarcoma, 2x undifferentiated sarcoma


Age: 11 and 16 years of age

Gender: 2 females


InterventionsHigh-dose chemotherapy (HDCT): thiotepa 900 mg/m2 total dose

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow or peripheral blood (not specified for each included case)


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Lashkari 2009

MethodsDuration: 1995 to 1999

Study design: prospective report of 13 cases without control

Treatment: number of arms: 1

Follow-up time: 99 and 138 months


ParticipantsSetting: single center in the United States

Eligibility criteria: locally advanced or metastatic sarcoma

Number of participants: 13 patients

  • 1 transplanted patients: 1x malignant fibrous histiocytoma, (included in the present review)
  • not included in the present review: 11x transplanted patients with diagnoses other than NRSTS: 7x Ewing family of tumors, 4x rhabdomyosarcoma, 1x undifferentiated sarcoma


Age: 40 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): doxorubicin 150 mg/m2, ifosfamide 14000 mg/m2, melphalan 150 mg/m2, cisplatin 200 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: progression-free survival reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Lippe 2003

MethodsDuration: not specified

Study design: retrospective report of 2 cases without control

Treatment: number of arms: 1

Follow-up time: 34 months after diagnosis


ParticipantsSetting: single center in Italy

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 2 patients

  • 1 transplanted patient with desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 1x desmoplastic small round-cell tumor without transplantation


Age: 27 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): cyclophosphamide 7000 mg/m2, total dose

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Livaditi 2006

MethodsDuration: not specified

Study design: retrospective report of 5 cases without control

Treatment: number of arms: 1

Follow-up time: 11 months and 15 months


ParticipantsSetting: single center in Greece

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 5 patients

  • 2 transplanted patients with desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 3x desmoplastic small round-cell tumor without transplantation


Age: 7 and 13 years

Gender: 1 male and 1 female


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Madigan 2007

MethodsDuration: 1983 to 2003

Study design: retrospective report of 14 cases without control

Treatment: number of arms: 1

Follow-up time: 34 months and 104 months after diagnosis


ParticipantsSetting: single center in the United States

Eligibility criteria: extracranial rhabdoid tumors

Number of participants: 14 patients

  • 1 transplanted patients with extracranial, extrarenal rhabdoid tumor (included in the present review)
  • not included in the present review: 12x extracranial rhabdoid tumors without transplantation, 1x extracranial but renal rhabdoid tumor with transplantation


Age: 30 months of age

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: not specified


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Matsuzaki 2002

MethodsDuration: in 1999

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in Japan

Eligibility criteria: synovial sarcoma

Number of participants: 1 patients

  • 1 transplanted patients with synovial sarcoma (included in the present review)


Age: 11 years of age

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Mazuryk 1998

MethodsDuration: in 1996

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 19 months


ParticipantsSetting: single center in Canada

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 1 patient

  • 1 transplanted patients with desmoplastic small round-cell tumor (included in the present review)


Age: 19 years of age

Gender: 1 female


InterventionsHigh-dose chemotherapy (HDCT): busulfan 16 mg/kg and melphalan 140 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Mingo 2005

MethodsDuration: not stated

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 12 months


ParticipantsSetting: single center in Spain

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 1 patient

  • 1 transplanted patients with desmoplastic small round-cell tumor (included in the present review)


Age: 4 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): etoposide, vincristine, ifosfamide, dactinomycin, and doxorubicin

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Mitchell 1994

MethodsDuration: not specified

Study design: report of 11 cases without control, unclear if retrospective or prospective study

Treatment: number of arms: 1

Follow-up time: 6 months regarding the included patient

Unclear if retrospective or prospective study without controls in a single centre, observed in the United Kingdom; information on observation period not available


ParticipantsSetting: single center in the United Kingdom

Eligibility criteria: malignant disease

Number of participants: 11 patients

  • 1 transplanted patients with angiosarcoma (included in the present review)
  • not included in the present review: 5x Ewing family of tumors, 3x rhabdomyosarcoma, 1x acute myeloid leukemia, 1x T-cell lymphoma


Age: 16 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT):

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow and peripheral blood in addition


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskUnclear if retrospective and no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Navid 2006

MethodsDuration: 1996 to 2000

Study design: retrospective report of 24 cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the United States

Eligibility criteria: high-risk sarcomas

Number of participants: 24 patients

  • 2 transplanted patients with desmoplastic small round-cell tumor (included in the present review)
  • not included in the present review: 2 patients with desmoplastic small round-cell tumor not transplanted
  • not included in the present review: 20 patients with diagnoses other than NRSTS: 11x Ewing family of tumors, 9x rhabdomyosarcoma


Age: 14 and 21 years

Gender: 2 males


InterventionsHigh-dose chemotherapy (HDCT): cyclophosphamide and targeted topotecan

Autologous hematopoietic stem cell transplantation (HSCT):

  • stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Patel 2004

MethodsDuration: 1994 to 2001

Study design: prospective report of 37 cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the United States

Eligibility criteria: skeletal osteosarcoma and variant bone tumors with poor prognosis

Number of participants: 37 patients

  • 6 transplanted patients with malignant fibrous histiocytoma (included in the present review)
  • not included in the present review: 29 patients with diagnoses other than NRSTS: 29x osteosarcoma, 2x chondrosarcoma


Age: not specified

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): cisplatin 120 mg/m2, ifosfamide 10000 mg/m2, and doxorubicin 75 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival was not reported for the 6 individual cases

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed

The following conclusion might not clearly substantiated by the presented data: Supplemental table 2: 14 HDCT plus autologous HSCT; 18 conventional chemotherapy. Text: "HDC seemed to delay relapse, but did not appear to prolong survival: 2-year EFS 17.9 +/- 11.3% versus 13.2 +/- 8.1%, P < 0.035 and OS 51.4 +/- 14.4% versus 50.9 +/- 11.6%, P value0.99. Two-year survival was 51.4 +/- 14.4% versus 48.6 +/- 16.7% P value 0.57 for patients treated with HDC (24 pts) versus conventional adjuvant chemotherapy (12 pts), respectively."


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Peters 1986

MethodsDuration: not specified

Study design: prospective report of cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the United States

Eligibility criteria: metastatic cancer and sarcoma

Number of participants: 29 patients

  • 2 transplanted patients with NRSTS: 1x fibrosarcoma, 1x leiomyosarcoma (included in the present review)
  • not included in the present review: 27 patients with diagnoses other than NRSTS


Age: 24 and 38 years

Gender: 2 females


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Peters 1989

MethodsDuration: not specified

Study design: prospective report of cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the United States

Eligibility criteria: metastatic cancer and sarcoma

Number of participants: 23 patients

  • 2 transplanted patients synovial sarcoma (included in the present review)
  • not included in the present review: 23 patients with diagnoses other than NRSTS


Age: 15 and 26 years

Gender: not specified


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow


OutcomesSecondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Philippe-Chomette 2012

MethodsDuration: 1995 to 2006

Study design: retrospective of cases without concurrent control

Treatment: number of arms: 1

Follow-up time: median of 49 months (range 9 to 108) for survivors


ParticipantsSetting: multicenter study in France and Belgium

Eligibility criteria: desmoplastic small round-cell tumor (DSRCT) diagnosed by the presence of the diagnostic genetic marker designated the Ewing sarcoma and Wilms tumor (EWS-WT1) fusion transcript originating at a chromosomal translocation breakpoint specific for DSRCT; patients under the age of 30 years; clinical data available

Number of participants: 14 patients

  • 14 transplanted patients (included in the present review)


Age: range (4 to 29.7 years for 38 participants)

Gender: 12 males and 2 females


InterventionsHigh-dose chemotherapy (HDCT): various regimens

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: not specified


OutcomesPrimary outcomes: overall survival as aggregate data; treatment-related mortality as individual data

Secondary outcomes: event-free survival as aggregate data; the first event of progression or relapse was taken into account for calculation of event-free survival.


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Recchia 2006

MethodsDuration: not specified

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 48 months


ParticipantsSetting: single center in Italy

Eligibility criteria: malignant fibrous histiocytoma

Number of participants: 1 patient

  • 1 transplanted patients with malignant fibrous histiocytoma (included in the present review)


Age: 40 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): cyclophosphamide 4500 mg/m2, carboplatin 1000 mg/m2, and etoposide 1500 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Saab 2007

MethodsDuration: not specified

Study design: retrospective report of 11 cases without control

Treatment: number of arms: 1

Follow-up time: from diagnosis


ParticipantsSetting: single center in the United States

Eligibility criteria: desmoplastic small round-cell tumor

Number of participants: 11 patients

  • 4 transplanted patients with desmoplastic small round-cell tumor (included in the present review)


Age: 5, 14, 18, and 21 years

Gender: 4 males


InterventionsHigh-dose chemotherapy (HDCT)

  • 2 patients: cyclophosphamide and topotecan
  • 1 patient: cyclophosphamide and etoposide
  • 1 patient: busulphan and melphalan


Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: not specified


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: toxicity reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Slease 1988

MethodsDuration: not specified

Study design: retrospective report of cases without control

Treatment: number of arms: 1

Follow-up time: not specified


ParticipantsSetting: single center in the United States

Eligibility criteria: refractory malignant solid tumors

Number of participants: 26 patients

  • 3 transplanted patients: 2x malignant fibrous histiocytoma, 1x leiomyosarcoma (included in the present review)
  • not included in the present review: 23 patients with diagnoses other than NRSTS


Age: 41, 45, 47 years

Gender: 3 males


InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: bone marrow


OutcomesPrimary outcomes: overall survival

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Sung 2003

MethodsDuration: 1998 to 2001

Study design: prospective report of 26 cases without control

Treatment: number of arms: 1

Follow-up time: 19, 45, and 45 months regarding the included patients


ParticipantsSetting: single center study in Korea

Eligibility criteria: high-risk malignant solid tumors

Number of participants: 26 patients

  • 2 transplanted patients: 1x clear cell sarcoma; 1x malignant fibrous histiocytoma (included in the present review)
  • not included in the present review: 24 patients with diagnoses other than NRSTS: 15x neuroblastoma, 3x medulloblastoma, 2x brain stem glioma, 1x glioblastoma multiforme, 1x Ewing family of tumors, 1x astrocytoma, 1x rhabdoid sarcoma, primary location not specified


Age: 20 and 48 months of age

Gender: 2 males


InterventionsHigh-dose chemotherapy (HDCT): successive double HDCT

  • clear cell sarcoma: melphalan, etoposide, carboplatin, total body irradiation/cyclophosphamide, etoposide
  • rhabdoid sarcoma: melphalan, etoposide, carboplatin/ifosfamide, carboplatin, etoposide
  • malignant fibrous histiocytoma: carboplatin, etoposide, melphalan/ifosfamide, carboplatin, etoposide


Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskProspective but no relevant aggregate data

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Yamamura 2003

MethodsDuration: in 1996

Study design: retrospective report of a single case without control

Treatment: number of arms: 1

Follow-up time: 4 months following diagnosis


ParticipantsSetting: single center study in Japan

Eligibility criteria: rhabdoid sarcoma

Number of participants: 1 patient

  • 1 transplanted patients with malignant fibrous histiocytoma (included in the present review)


Age: 33 years of age

Gender: 1 male


InterventionsHigh-dose chemotherapy (HDCT): tandem HDCT: ifosfamide 6000 mg/m2, carboplatin 1200 mg/m2, etoposide 1200 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesPrimary outcomes: overall survival reported as individual data

Secondary outcomes: adverse events (development of chronic myelocytic leukemia following chemotherapy) reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

Yonemoto 1999

MethodsDuration: in 1995

Study design: retrospective report of 3 cases without control

Treatment: number of arms: 1

Follow-up time: 6, 6, and 8 months regarding the included patients


ParticipantsSetting: single center study in Japan

Eligibility criteria: sarcomas

Number of participants: 10 patients

  • 3 transplanted patients with synovial sarcoma (included in the present review)
  • not included in the present review: 7 patients with diagnoses other than NRSTS: 6x Ewing family of tumors, 1x osteosarcoma


Age: 17, 28, and 40 years of age regarding the included patients

Gender: 3 males regarding the included patients


InterventionsHigh-dose chemotherapy (HDCT): tandem HDCT: busulfan 16 mg/kg, melphalan 140 mg/m2, thiotepa 600 mg/m2, total doses

Autologous hematopoietic stem cell transplantation (HSCT)

  • stem cell source: peripheral blood


OutcomesSecondary outcomes: adverse events reported as individual data


NotesFinancial support: not addressed


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskNo randomization

Allocation concealment (selection bias)High riskNo allocation concealment

Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessor was not reported for any outcome

Selective reporting (reporting bias)Unclear riskNo protocol available

Prospective designHigh riskRetrospective

Comparable baseline characteristicsHigh riskCases without control

Assignment of patients to treatment groupsHigh riskSingle-arm study

Concurrent controlHigh riskNo control

Loss to follow-upUnclear riskPossible but not reported

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Abdel-Dayem 1999not intervention of interest

Abrahamsen 2000not diagnosis of interest (histological types of sarcoma not specified)

Aleinikova 2002not diagnosis of interest

Amarti 1995not intervention of interest

Antman 1990not diagnosis of interest (data not reported separately)

Arancibia 2009not diagnosis of interest (data not reported separately)

Atra 1996not diagnosis of interest

Atra 2002not diagnosis of interest

Ayash 1991not publication type of interest (review)

Baker 1987not intervention of interest

Banna 2007not publication type of interest (review)

Beaujean 1987not diagnosis of interest (data not reported separately)

Bechter 2009not publication type of interest (review)

Bien 2007not diagnosis of interest

Bokemeyer 1994anot intervention of interest

Bokemeyer 1994bnot intervention of interest

Borden 1987not intervention of interest

Borinstein 2009not intervention of interest

Bouligand 2007not diagnosis of interest

Bramwell 1986not diagnosis of interest (data not reported separately)

Bramwell 1987not intervention of interest

Brugger 1993not intervention of interest

Chandrakasan 2011not intervention of interest

Chang 1988not intervention of interest

Chen 2004not diagnosis of interest

Childs 2004not publication type of interest (review)

Chitalkar 2009not diagnosis of interest (data not reported separately)

Chuman 2000not publication type of interest (review)

Chuman 2004not diagnosis of interest (data not reported separately)

Church 2006not intervention of interest

Clamon 1983not intervention of interest

Coulibalya 2008not intervention of interest

Crist 1987not intervention of interest

Cunningham 1994not intervention of interest

Czyzewski 1999not diagnosis of interest (data not reported separately)

Dantonello 2010not diagnosis of interest (data not reported separately)

Devalck 1992not publication type of interest (review)

Duffaud 2005not diagnosis of interest

Dumontet 1992not diagnosis of interest (data not reported separately)

Edmonson 1993not intervention of interest

Ehlert 2012not diagnosis of interest (data not reported separately)

Ek 2006not publication type of interest (review)

Elias 1998not publication type of interest (review)

Endo 1996not diagnosis of interest (undifferentiated sarcoma)

Ettinghausen 1986not intervention of interest

Fayette 2009not intervention of interest

Ferrari 2005not intervention of interest (one patient with HSCT not reported separately)

Figuerres 2000not diagnosis of interest (data not reported separately)

Fine 2007not intervention of interest

Florine 1988not diagnosis of interest

Frapier 1998not diagnosis of interest (undifferentiated sarcoma)

Frustaci 2001not intervention of interest

Gadner 1992not diagnosis of interest (data not reported separately)

Gadner 2002not diagnosis of interest

Gamillscheg 1991not diagnosis of interest (data not reported separately)

Garcia-del-Muro 2011not intervention of interest

Ghavamzadeh 2011not diagnosis of interest (data not reported separately)

Gooskens 2011not diagnosis of interest

Gorin 1981not diagnosis of interest

Gortzak 2001not intervention of interest

Goto 2004not publication type of interest (review)

Gratwohl 2004anot diagnosis of interest (data not reported separately)

Gratwohl 2004bnot diagnosis of interest (data not reported separately)

Gratwohl 2006not diagnosis of interest (data not reported separately)

Gu 2004not diagnosis of interest

Halperin 1984not intervention of interest

Hara 1998not diagnosis of interest (rhabdomyosarcoma)

Harada 1982not diagnosis of interest (data not reported separately)

Hartmann 1984not diagnosis of interest

Hartmann 1997not diagnosis of interest (data not reported separately)

Hayes-Jordan 2009not publication type of interest (review)

Hayes-Jordan 2012not publication type of interest (review)

He 1999not intervention of interest

Hernandez 1999not intervention of interest

Herzog 2005not publication type of interest (review)

Hibi 1993not intervention of interest

Hoeffken 1997not diagnosis of interest (data not reported separately)

Honda 2011not diagnosis of interest

Horiuchi 2005not diagnosis of interest

Hubbard 1977not intervention of interest

Hutspardol 2012not diagnosis of interest

Ivanova 2010not diagnosis of interest (data not reported separately)

Iyer 2013not intervention of interest

Jamil 2004not diagnosis of interest (data not reported separately)

Jebson 2004not intervention of interest

Jelic 1997not intervention of interest

Kabickova 2003not diagnosis of interest (data not reported separately)

Kallianpur 2012not publication type of interest (review)

Kaminski 2000not diagnosis of interest (intracranial)

Kampe 1993not intervention of interest

Kasper 2005not publication type of interest (review)

Kasper 2006not publication type of interest (duplicate data included in follow-up paper Kasper 2008)

Katzenstein 2003not diagnosis of interest

Kingston 1984not diagnosis of interest

Kinsella 1988not diagnosis of interest (data not reported separately)

Kinugawa 1995not intervention of interest

Kiss 2009not diagnosis of interest (data not reported separately)

Klein 1983not intervention of interest

Klingebiel 2008not diagnosis of interest (data not reported separately)

Koscielniak 1997not diagnosis of interest

Koscielniak 1999not intervention of interest

Koscielniak 2002not publication type of interest (review)

Kuehne 2000not diagnosis of interest

Kushner 2000not intervention of interest (data not reported separately)

Kwon 2010not diagnosis of interest

Ladenstein 1997not diagnosis of interest (data not reported separately)

Lal 2005not intervention of interest (data not reported separately)

Lasalvia-Prisco 2012not diagnosis of interest (data not reported separately)

Le Cesne 2000not intervention of interest

Leyvraz 2006not intervention of interest

Lorigan 2007not intervention of interest

Macak 2003not intervention of interest

Makris 2009not intervention of interest

Maraninchi 1984not diagnosis of interest

Maurel 2009not intervention of interest

Mesia 1994not diagnosis of interest (undifferentiated sarcoma)

Minard-Colin 2004not intervention of interest

Mohensy 2011not intervention of interest

Mueller 2002not diagnosis of interest

Nachbaur 1994not diagnosis of interest

Nag 1995not intervention of interest (radiotherapy)

Nakamura 2008not diagnosis of interest (undifferentiated sarcoma)

Nath 2005not diagnosis of interest

Nemet 1990not diagnosis of interest

Nemet 1999not diagnosis of interest

Nickerson 2004not intervention of interest

Nieboer 2005not diagnosis of interest

Nieto 1999not publication type of interest (review)

Nieto 2004not publication type of interest (review)

Nieto 2007not diagnosis of interest (data not reported separately)

Ninomiya 1988not diagnosis of interest (data not reported separately)

Nivison-Smith 2005not diagnosis of interest (data not reported separately)

Odile 2008not intervention of interest

Ortega 1991not diagnosis of interest

Oue 2010not diagnosis of interest

Ozkaynak 2008not diagnosis of interest

Palumbo 1997not intervention of interest

Pasetto 2003not publication type of interest (review)

Passweg 2012not outcome of interest

Patel 1992not publication type of interest (review)

Patel 1998not intervention of interest

Perez-Gracia 2001not diagnosis of interest (data not reported separately)

Perez-Martinez 2003not intervention of interest

Perez-Martinez 2011not intervention of interest

Pick 1988not publication type of interest (review)

Pinkerton 1991not diagnosis of interest

Pohlodek 1994not outcome of interest

Radulescu 2008not diagnosis of interest

Rapidis 2008not publication type of interest (review)

Ray-Coquard 2001not publication type of interest (review)

Reichardt 1998not intervention of interest

Rich 1980not diagnosis of interest

Ronghe 2004not diagnosis of interest (rhabdoid tumor without information about localisation)

Rupolo 2001not intervention of interest

Rzepecki 2006not diagnosis of interest (data not reported separately)

Samma 1994not diagnosis of interest

Sano 2012not intervention of interest

Santoro 1995not diagnosis of interest

Sawyer 1999not publication type of interest (review)

Schellong 1981not publication type of interest (review)

Schilder 1999not diagnosis of interest

Schilder 2001not diagnosis of interest

Schimmer 2002not diagnosis of interest (data not reported separately)

Schlegel 2009not intervention of interest

Schlemmer 2006not diagnosis of interest (data not reported separately)

Schuster 2008not diagnosis of interest (data not reported separately)

Schwartzberg 1993not diagnosis of interest

Schwella 1998not diagnosis of interest (data not reported separately)

Seibel 2004not intervention of interest

Seynaeve 1999not publication type of interest (review)

Shaw 1996not diagnosis of interest (undifferentiated sarcoma; rhabdoid tumor without information about localisation)

Shen 1993not diagnosis of interest

Shenoy 2010not diagnosis of interest

Shvarova 2009not intervention of interest

Slovacek 2007not publication type of interest (review)

Somers 2006not diagnosis of interest (histologic type not specified for individual data)

Sudo 1991not intervention of interest

Tajima 1983not diagnosis of interest

Tajima 1988not diagnosis of interest

Takeda 1995not disease of interest

Taskinen 1998not diagnosis of interest

Termuhlen 2006not disease of interest

Tursz 1996not intervention of interest

Unruh 1979not intervention of interest

Van Glabbeke 1993not intervention of interest

Verma 2002not publication type of interest (review)

Verma 2008anot publication type of interest (systematic review)

Verma 2008bnot publication type of interest (review)

Verweij 2000not intervention of interest

Walker 2004not intervention of interest

Watanabe 2006not diagnosis of interest (rhabdoid tumor without information about localisation)

Webber 2007not intervention of interest

Weh 1996not intervention of interest

Woods 1999not publication type of interest (review)

Yamada 1999not diagnosis of interest

Yaqoob 2006not publication type of interest (review)

Yeung 1994not diagnosis of interest

Yokoyama 1993not intervention of interest

Yumura-Yagi 1998not diagnosis of interest

Zoubek 1994not intervention of interest

 
Characteristics of ongoing studies [ordered by study ID]
NCT00002601

Trial name or titleTitle: Combination chemotherapy and peripheral stem cell transplantation in treating patients with sarcoma

Official Title: High-dose doxorubicin and ifosfamide followed by melphalan and cisplatin for patients with high-risk and recurrent sarcoma

MethodsStudy start date: September 1994

Estimated primary completion date: March 2013

Study design: Intervention model: single group assignment; Masking: open label; Primary purpose: treatment

Treatment: number of arms: 1

Follow-up time: 2 years after completion of treatment

ParticipantsSetting: single center in the United States: City of Hope

Eligibility criteria: 10 to 55 years of age; patients with high risk or advanced soft tissue sarcoma, osteosarcoma, Ewing family of tumors, or rhabdomyosarcoma; Karnofsky performance status 80% to 100%; other criteria apply

Estimated enrollment: 20 patients

InterventionsHigh-dose chemotherapy (HDCT): cisplatin, doxorubicin, ifosfamide, melphalan

Autologous hematopoietic stem cell transplantation (HSCT): stem cell source: peripheral blood

OutcomesOverall survival, disease-free survival, response, toxicity, feasibility of administration of 2 cycles of high-dose chemotherapy followed by autologous HSCT

Starting dateSeptember 1994

This study is ongoing, but not recruiting participants

Contact informationStudy chair: George Somlo, MD, City of Hope, Beckman Research Institute, Duarte, California, United States

NotesFinancial support: non-profit organization

NCT00002854

Trial name or titleTitle: High-dose combination chemotherapy plus peripheral stem cell transplantation in treating patients with advanced cancer

Official Title: Phase I pilot study of sequential high-dose cycles of cisplatin, cyclophosphamide, etoposide and ifosfamide, carboplatin and taxol with autologous stem cell support

MethodsStudy start date: December 1994

Estimated primary completion date: February 2013

Study design: Intervention model: single group assignment; Masking: open label; Primary purpose: treatment

Treatment: number of arms: 1

Follow-up time: for at least 5 years after completion of treatment

ParticipantsSetting: single center in the United States: City of Hope

Eligibility criteria: 18 to 55 years of age; patients with primary soft tissue sarcoma with high-grade disease greater than 10 cm or that is metastatic, osteosarcoma, breast carcinoma, ovarian cancer, malignant melanoma, metastaticsmall cell bone carcinoma, metastaticEwing family of tumors, metastaticgastrointestinal malignancy or recurrent Wilms tumor; Karnofsky performance status 80% to 100%; other criteria apply

Estimated enrollment: 6 patients

InterventionsHigh-dose chemotherapy (HDCT): cisplatin, cyclophosphamide, etoposide and ifosfamide, carboplatin and taxol

Autologous hematopoietic stem cell transplantation (HSCT): stem cell source: peripheral blood

OutcomesToxicity, feasibility of administration of 2 cycles of high-dose chemotherapy followed by autologous HSCT

Starting dateSeptember 1994

This study is ongoing, but not recruiting participants

Contact informationStudy chair: George Somlo, MD, City of Hope, Beckman Research Institute, Duarte, California, United States

NotesFinancial support: non-profit organization

NCT00141765

Trial name or titleTitle: Study of high-dose chemotherapy with bone marrow or stem cell transplant for rare poor-prognosis cancers

Official Title: High-dose doxorubicin and ifosfamide followed by melphalan and cisplatin for patients with high-risk and recurrent sarcoma

MethodsStudy start date: January 1997

Estimated primary completion date: January 2014

Study design: Intervention model: single group assignment; Masking: open label; Primary purpose: treatment

Treatment: number of arms: 1

Follow-up time: 1 year after completion of treatment

ParticipantsSetting: single center in the United States: The University of Michigan

Eligibility criteria: 21 years old or younger, histologically-confirmed Wilms tumor, liver cancer, recurrent brain tumor of childhood, nasopharyngeal carcinoma, fibrosarcoma, desmoplastic small round cell tumor, germ cell tumor or other small round cell tumor, which: is metastatic and has <25% cure rate with conventional treatment or progressed after prior chemotherapy and has <25% salvage rate with non-myeloablative therapies; other criteria apply

Estimated enrollment: not stated

InterventionsHigh-dose chemotherapy (HDCT): cyclophosphamide, ifosfamide, carboplatin and thiotepa

Autologous hematopoietic stem cell transplantation (HSCT): stem cell source: peripheral blood

OutcomesDisease-free survival

Starting dateJanuary 1997

This study is ongoing, but not recruiting participants

Contact informationPrincipal investigator: John E Levine, MS MD, The University of Michigan, Ann Arbor, Michigan, United States

NotesFinancial support: non-profit organization

NCT00623077

Trial name or titleTitle: Total marrow irradiation added to an alkylator-intense conditioning regimen for patients with high risk or relapsed solid tumors

Official Title: Dose escalation of total marrow irradiation added to an alkylator-intense conditioning regimen for patients with high risk or relapsed solid tumors

MethodsStudy start date: August 2005

Estimated primary completion date: June 2014

Study design: Endpoint classification: safety/efficacy study; Intervention model: single group assignment; Masking: open label; Primary purpose: treatment

Treatment: number of arms: 1

Follow-up time: not stated

ParticipantsSetting: single center in the United States: University of Minnesota, Masonic Cancer Center

Eligibility criteria: up to 70 years; patients with high risk or relapsed malignancies that include: Ewing family of tumors, Wilms tumor, clear cell sarcoma, rhabdoid tumor, hepatoblastoma, rhabdomyosarcoma, soft tissue sarcoma, primary malignant brain neoplasm, retinoblastoma; other criteria apply

Estimated enrollment: 45 patients

InterventionsTotal marrow irradiation with tomotherapy

High-dose chemotherapy (HDCT): busulfan, melphalan, thiotepa

Autologous hematopoietic stem cell transplantation (HSCT): stem cell source: peripheral blood

OutcomesPrimary Outcome Measures: Maximum tolerated dose of tomotherapy up to 12 Gy

Secondary Outcome Measures: Overall survival, disease-free survival, rate of treatment-related mortality

Starting dateAugust 2005

This study is ongoing, but not recruiting participants

Contact informationPrincipal investigator: Michael R Verneris, MD, University of Minnesota, Masonic Cancer Center, Minneapolis, Minnesota, United States

NotesFinancial support: non-profit organization

NCT00638898

Trial name or titleTitle: Busulfan, melphalan, topotecan hydrochloride, and a stem cell transplant in treating patients with newly diagnosed or relapsed solid tumor

Official Title: Pilot study of high-dose chemotherapy with busulfan, melphalan, and topotecan followed by autologous hematopoietic stem cell transplant in advanced stage and recurrent tumors

MethodsStudy start date: December 2006

Estimated primary completion date: April 2019

Study design: Endpoint classification: efficacy study; Intervention model: single group assignment; Masking: open label; Primary purpose: treatment

Treatment: number of arms: 1

Follow-up time: After completion of study treatment, patients are followed every 3 months for 1 year and then annually thereafter

ParticipantsSetting: single center in the United States: City of Hope

Eligibility criteria: up to 70 years; patients with relapsed neuroblastoma, rhabdomyosarcoma, Ewing family of tumor, brain tumor, soft tissue sarcomas Wilms tumor, germ cell tumor or other solid tumor who achieved at least partial response to chemotherapy, surgery, or radiotherapy; other criteria apply

Estimated enrollment: 25 patients

InterventionsHigh-dose chemotherapy (HDCT): busulfan, melphalan, topotecan

Autologous hematopoietic stem cell transplantation (HSCT): stem cell source: peripheral blood

OutcomesPrimary Outcome Measures: Treatment feasibility in terms of investigational agent-related adverse events of a novel treatment combination followed by peripheral blood stem cell rescue

Secondary Outcome Measures: Overall survival, disease-free survival, Incidence of myeloid and platelet engraftment

Starting dateDecember 2006

This study is currently recruiting participants

Contact informationPrincipal investigator: Anna Pawlowska, MD, City of Hope, Duarte, California, United States

NotesFinancial support: non-profit organization

NCT01288573

Trial name or titleTitle: A combined study in pediatric cancer patients for dose ranging and efficacy/safety of plerixafor plus standard regimens for mobilization versus standard regimens alone

Official Title: A phase 1/2 combined dose ranging and randomized, open-label, comparative study of the efficacy and safety of plerixafor in addition to standard regimens for mobilization of haematopoietic stem cells into peripheral blood, and subsequent collection by apheresis, versus standard mobilization regimens alone in pediatric patients, aged 2 to <18 years, with solid tumours eligible for autologous transplants

MethodsStudy start date: February 2011

Estimated primary completion date: May 2017

Study design: Allocation: randomized; Endpoint classification: safety/efficacy study; Intervention model: parallel assignment; Masking: open label; Primary purpose: treatment

Treatment: number of arms: 2

Follow-up time: up to 24 months after completion of study treatment

ParticipantsSetting: multicenter trial in France, Germany, Italy, and the United Kingdom

Eligibility criteria: 2 to 18 years of age; patients with Ewing family of tumor, soft tissue sarcoma, neuroblastoma, brain tumors or other malignancy (excluding any form of leukemia) requiring treatment with high dose chemotherapy and autologous transplant as rescue therapy; other criteria apply

Estimated enrollment: 67 patients

InterventionsHigh-dose chemotherapy (HDCT): not specified

Autologous hematopoietic stem cell transplantation (HSCT): stem cell source: peripheral blood

OutcomesPrimary Outcome Measures: Proportion of patients achieving at least a doubling of peripheral blood CD34+ count during Stage 2

Secondary Outcome Measures: Survival rates

Starting dateFebruary 2011

This study is currently recruiting participants

Contact informationStudy director: Medical Monitor, Genzyme Corporation (sponsor of the trial)

NotesFinancial support: Genzyme Corporation (biotechnology company)

 
Summary of findings for the main comparison. Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcoma

Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcoma

Patient or population: patients with non-rhabdomyosarcoma soft tissue sarcoma
Settings: Spezialized hospital
Intervention: Autologous hematopoietic stem cell transplantation following high-dose chemotherapy
Comparison: standard-dose chemotherapy

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Standard-dose chemotherapyAutologous hematopoietic stem cell transplantation following high-dose chemotherapy

Overall survival
Follow-up: median 55 months
489 per 1000571 per 1000
(375 to 785)
HR 1.26
(0.7 to 2.29)
83
(1 study)
⊕⊕⊕⊕
high

Progression-free survival
Follow-up: median 55 months
756 per 1000849 per 1000
(681 to 955)
HR 1.34
(0.81 to 2.2)
83
(1 study)
⊕⊕⊕⊕
high

Treatment-related mortalitySee commentSee commentNot estimable163
(12 studies1)
⊕⊝⊝⊝
very low
case series; 15 events in 0 subjects

Health-related quality of lifeSee commentSee commentNot estimable-See commentnot reported

Disease-free survival
Follow-up: 3 years
See commentSee commentNot estimable0
(1 study1)
⊕⊝⊝⊝
very low1
case series; 0 events in 0 subjects

Non-hematological toxicity grade 3 to 4See commentSee commentNot estimable105
(9 studies1)
⊕⊝⊝⊝
very low1
case series; 38 events in 0 subjects

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 case series
 
Table 1. Frequency of subtypes of included NRSTS in patients of young versus advanced age

Young age (< 20 years)Advanced (≥ 20 years)


Subtype%Subtype%

Synovial sarcoma7.7Leiomyosarcoma13.7

Malignant fibrous histiocytoma4.9Malignant fibrous histiocytoma10.1

Fibrosarcoma4.5Liposarcoma8.0

Liposarcoma2.8Hemangiosarcoma2.5

Epitheloid sarcoma2.0Spindle cell sarcoma2.3

 Estimates in the table according to Spunt 2006
 
Table 2. Included non-rhabdomyosarcoma soft tissue sarcomas (NRSTS)

Diagnosis(*)

Alveolar soft part sarcoma

Anaplastic soft tissue sarcoma

Angiosarcoma

  1. Angiosarcoma of soft tissue
  2. Hemangiosarcoma
  3. Hemangiopericytoma
  4. Lymphangiosarcoma

Clear cell myomelanocytic tumor

Clear cell sarcoma of soft tissue

Desmoplastic small round cell tumor

Epithelioid sarcoma

Fibrosarcoma

  1. Adult fibrosarcoma
  2. Myxofibrosarcoma
  3. Low grade fibromyxoid sarcoma; hyalinizing spindle cell tumor
  4. Sclerosing epithelioid fibrosarcoma

Fibromyxoid sarcoma

Epithelioid hemangioendothelioma

Intimal sarcoma

Leiomyosarcoma

  1. Leiomyosarcoma (excluding skin)

Liposarcoma

  1. Dedifferentiated liposarcoma
  2. Myxoid liposarcoma
  3. Round cell liposarcoma
  4. Pleomorphic liposarcoma
  5. Mixed-type liposarcoma
  6. Liposarcoma, not otherwise specified (added by authors: chondroid liposarcoma)

Malignant fibrous histiocytoma

  1. Pleomorphic malignant fibrous histiocytoma; undifferentiated pleomorphic sarcoma
  2. Giant cell malignant fibrous histiocytoma; undifferentiated pleomorphic sarcoma with giant cells
  3. Inflammatory malignant fibrous histiocytoma; undifferentiated pleomorphic sarcoma with prominent inflammation
  4. Undifferentiated pleomorphic sarcoma
  5. Spindle cell sarcoma

Malignant glomus tumor

Malignant haemangiopericytoma

Malignant mesenchymoma

Mesenchymal sarcoma

Neoplasms with perivascular epithelioid cell differentiation (PEComa)

Rhabdoid sarcoma

  1. Extra-renal rhabdoid tumor
  2. Extra-cerebral rhabdoid tumor

Synovial sarcoma

 * category of malignant tumors according to the World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Soft Tissue and Bone (Fletcher 2002)
 
Table 3. Excluded tumor types

DiagnosisReason for exclusion(*)

Atypical teratoid/rhabdoid tumorsWHO classification of tumors of the central nervous system

Chondrosarcoma

  1. Mesenchymal chondrosarcoma
  2. Extraskeletal myxoid chondrosarcoma ('chordoid type')
Extraskeletal types are difficult to separate

Clear cell sarcoma of the kidneyExcluded by the authors of the present review

Dermatofibrosarcoma protuberansWHO classification of tumors of the skin

Endometrial stroma sarcomaWHO classification of tumors: pathology and genetics of tumors of the breast and female genital organs

Ewing family of tumors

  1. Ewing sarcoma
  2. Skeletal Ewing's sarcoma
  3. Extraskeletal Ewingsarcoma
  4. Peripheral primitive neuroectodermal tumour (pPNET)
  5. Extraskeletal peripheral primitive neuroectodermal tumor (pPNET)
  6. Askin tumor
Extraskeletal types are difficult to separate; the Ewing family of tumors is one entity

Extragonadal germ cell sarcomaWHO classification of tumors: pathology and genetics of tumors of the urinary system and male genital organs

WHO classification of tumors: pathology and genetics of tumors of the breast and female genital organs

Follicular dendritic cell sarcomaWHO classification of tumors of hematopoietic and lymphoid tissues

GanglioneuroblastomaWHO classification of nervous system tumors

Gastrointestinal stromal tumorWHO classification of tumors: pathology and genetics of tumors of the digestive system

Giant cell fibroblastomaWHO classification of tumors of the skin

Giant cell tumour of boneWHO classification for tumors of bone tissue

Histiocytic sarcomaWHO classification of tumors of hematopoietic and lymphoid tissues

Interdigitating dendritic cell sarcomaWHO classification of tumors of hematopoietic and lymphoid tissues

Interdigitating reticulum cell sarcomaWHO classification of tumors of hematopoietic and lymphoid tissues

Kaposi sarcomaIntermediate malignancy (rarely metastasizing)

Lymphoblastic lymphosarcomaWHO classification of tumors of hematopoietic and lymphoid tissues

Malignant ectomesenchymomaExcluded by the authors of the present review

MedulloblastomaWHO classification of tumors of the central nervous system

Myeloid sarcomaWHO classification of tumors of hematopoietic and lymphoid tissues

Myxosarcoma (cardiac tumor)WHO classification of tumors: pathology and genetics of tumors of the lung, pleura, thymus and heart

NephroblastomaWHO classification of tumors: pathology and genetics of tumors of the urinary system and male genital organs

Neuroblastoma (Wilms tumor)WHO classification of tumors: pathology and genetics of tumors of the urinary system and male genital organs

Osteosarcoma

  1. Extraskeletal osteosarcoma
Extraskeletal types are difficult to separate

ParagangliomaWHO classification of nervous system tumors

Peripheral nerve sheath tumor, malignant (neurofibrosarcoma)WHO classification of nervous system tumors

Rhabdoid tumor, renalWHO classification of tumors: pathology and genetics of tumors of the urinary system and male genital organs

Rhabdoid tumor, cerebralWHO classification of tumors of the central nervous system

Rhabdomyosarcoma

  1. Embryonal rhabdomyosarcoma (including spindle cell, botryoid, anaplastic)
  2. Alveolar rhabdomyosarcoma (including solid, anaplastic)
  3. Pleomorphic rhabdomyosarcoma
  4. Undifferentiated rhabdomyosarcoma
A soft tissue sarcoma that is excluded to separate rhabdomyosarcomas from non-rhabdomyosarcoma soft tissue sarcomas

Schwannoma, malignant (Schwannosarcoma)WHO classification of nervous system tumors

Stromal cell sarcomaNot part of the WHO classification of soft tissue sarcomas, malignant tumors

Unclassified sarcomaIt is not clear that the tumor is a non-rhabdomyosarcoma soft tissue sarcoma

Undifferentiated sarcomaIt is not clear that the tumor is a non-rhabdomyosarcoma soft tissue sarcoma

Uterine endometrial stromal sarcomaWHO classification of tumors: pathology and genetics of tumors of the breast and female genital organs

 * WHO: World Health Organization
 
Table 4. Included studies identified by only one search strategy

Old strategy (original)New strategy (update)

Bisogno 2010

Buerk 2010

Bui-Nguyen 2012

Cook 2012

Etienne-Mastroianni 2002

Fang 2008

Graham 1997

Hawkins 2002

Houet 2010

Jordan 2010

Kretschmar 1996

Krskova 2007

Matsuzaki 2002

Peters 1986

Peters 1989

Philippe-Chomette 2012

Slease 1988

 Eight studies were published after the original retrieval and were added to the included studies: Bisogno 2010; Buerk 2010; Bui-Nguyen 2012; Cook 2012; Etienne-Mastroianni 2002; Houet 2010; Jordan 2010; Philippe-Chomette 2012.
Nine further studies were included in the original review but were not identified by the new search strategy: Fang 2008; Graham 1997; Hawkins 2002; Kretschmar 1996; Krskova 2007; Matsuzaki 2002; Peters 1986; Peters 1989; Slease 1988. These 15 studies were included in the update in addition to the results of the new search strategy.
Three further studies were included in the original review and identified in the update but excluded after re-evaluation: Ivanova 2010; Kaminski 2000; Kuehne 2000.
Three further studies were excluded in the original review and identified in the update but included after re-evaluation: Blay 2000; Fetscher 1996; Mingo 2005.
Six further studies were included in the original review and not identified in the update but excluded after re-evaluation: Four studies reported about undifferentiated sarcoma, which is not included: Endo 1996; Frapier 1998; Mesia 1994; Nakamura 2008. One study reported about rhabdoid tumor but without information about the localisation, which is required for identification of the extra-renal and the extra-cerebral rhabdoid tumors: Ronghe 2004. One study reported about undifferentiated sarcoma and rhabdoid tumor without information about the localisation: Shaw 1996.
 
Table 5. Overview of included studies

StudyTotal, NDiagnosisStart of follow upProspectiveHDCT vs. SDCT, N analyzed

Not rel, N (%)Rel, NAffected patients, N; type of included diagnosis

Aggregate comparative data (HDCT & autologous HSCT vs. SDCT)

Bui-Nguyen 20128718 (20)6916x LMS, 16x MFH, 10x LPS, 9x SYN, 6x ANG, 2x UDS, 2x MME, 2x DSRCT, 2x FIB, 1x LMS, 1x UCS, 1x CCSRandomizationYES38 vs. 45 in ITT(*)

Subtotal comparative data in 1 study38 vs. 45


Aggregate case series data (HDCT & autologous HSCT only)

Bertuzzi 2003100 (0)1010x DSRCTTherapyYES10

Bisogno 2010140 (0)1414x DSRCTDiagnosisYES14

Blay 2000242 (10)2224x NRSTSTherapyYES24

Bokemeyer 1997182 (11)165x MFH, 4x HAP, 3x SYN, 2x LMS, 2x MESTherapyno16

Cook 2012360 (0)3636x DSRCTTherapyno36

Philippe-Chomettte 2012140 (0)1414x DSRCTDiagnosisno14

Subtotal case series in 6 studies114


Individual cases data (HDCT & autologous HSCT only)

Al Balushi 200933x DSRCTno3

Andres 200611x DSRCTno1

Bernbeck 200722x SYNno2

Bley 200411x LIPno1

Boelke 200511x MFHno1

Buerk 201011x MFHno1

Cole 199911x SYNno1

Doros 200811x DSRCTno1

Engelhardt 200735ANA, ANG, FIB, LMS, LIP, MFH, MHP, SYNno23

Etienne-Mastroianni 2002121x LMSno1

Fang 200821x DSRCTno1

Farruggia 200811x SYNno1

Fetscher 199611x LMSno1

Fetscher 199711x LMSno1

Fraser 2006364x DSRCTYES4

Garrido 199821x LIPno1

Graham 1997491x FIBYES1

Hara 201011x ANGno1

Hawkins 2002232x DSRCT, 1x FMS, 1x LMSYES6

Hoogerbrugge 199711x FIBno1

Houet 201011x DSRCTno1

Jordan 2010162x EPI, 1x SYN, 1x SCS, 1x LMS, 1x ANG, 1x HAPYES7

Kasper 2007a385x SYN, 3x LMS, 2x LIP 1x MFHno11

Kasper 201092x MFH, 1x LMS, 1x SYNYES4

Kozuka 200221x MFH, 1x MHPno2

Kretschmar 199631x DSRCTno1

Krskova 200711x SYNno1

Kurre 200022x DSRCTno2

Kushner 1996124x DSRCTYES4

Kushner 2001211x DSRCTYES1

Kushner 200811x DSRCTno1

Lafay-Cousin 2000182x DSRCTYES2

Lashkari 2009131x MFHYES1

Lippe 200321x DSRCTno1

Livaditi 200652x DSRCTno2

Madigan 2007141x RHAno1

Matsuzaki 200211x SYNno1

Mazuryk 199811x DSRCTno1

Mingo 200511x DSRCTno1

Mitchell 1994111x ANGno1

Navid 2006242x DSRCTno2

Patel 2004376x MFHYES6

Peters 1986291x FIB, 1x LMSYES2

Peters 1989232x SYNYES2

Recchia 200611x MFHno1

Saab 200744x DSCRTno4

Slease 1988262x MFH, 1x LMSno3

Sung 2003261x CCS, 1x MFHno2

Yamamura 200311x MFHno1

Yonemoto 1999103x SYNno3

Subtotal individual cases in 50 studies123


Summary of patient count


Subtotal HDCT & autologous HSCT in 57 studies275


Subtotal SDCT in 1 study45


Total in 57 studies320

 (*) modified ITT: histologically ineligible patients excluded from primary group of analysis; HDCT group: 3 of 41 randomized data excluded; SDCT group: 1 of 46 randomized data excluded
Abbreviations: Diag: diagnosis; HDCT: high-dose chemotherapy (& autologous hematopoietic stem cell transplantation); HR: hazard ratio; HSCT: hematopoietic stem cell transplantation; ITT: intention to treat; N: number of participants; Nspe: not specified; Prosp: prospective study design; Rand: randomization Rel: relevant; SDCT: standard-dose chemotherapy; Ther: therapy; vs.: versus
Diagnoses: ANA: anaplastic soft tissue sarcoma; ANG: angiosarcoma; CCS: clear cell sarcoma; DSRCT: desmoplastic small round-cell tumor; EPI: epitheloid sarcoma; FIB: fibrosarcoma; FMS: fibromyxoid sarcoma; HAP: hemangiopericytoma; LIP: liposarcoma; LMS: leiomyosarcoma; MES: mesenchymal sarcoma; MFH: malignant fibrous histiocytoma; MHP: malignant hemangioperiocytoma; MME: malignant myoepithelioma; NRSTS: various types of non-rhabdomyosarcoma soft tissues sarcomas; RHA: rhabdoid tumor; SCS: spindle cell sarcoma; SYN: synovial sarcoma; UCS: unclassified sarcoma; UDS: undifferentiated sarcoma
 
Table 6. Overall survival (OS)

StudyOS, % (95% CI)

All patients assessedComplete response before the time of HSCTNot complete response before the time of HSCT

Aggregate comparative data (HDCT & autologous HSCT vs. SDCT)

Bui-Nguyen 20123 years: 32.7% vs. 49.4%, HR 1.26 (0.70 to 2.29, P = 0.44)3 years: 42.8% vs. 83.9%, HR 2.92 (1.1 to 7.6, P = 0.028)Not reported

Aggregate case series data (HDCT & autologous HSCT only)

Bertuzzi 20032 years: 20%Not reportedNot reported

Bisogno 20102 years: 48%

3 years: 38.9%
Not reportedNot reported

Blay 2000Not reported2 years: 62%

5 years: 62%
2 years: 27%

5 years: 5%

Bokemeyer 1997Median 13 months (range 3 to 19)Not reportedNot reported

Cook 20123 years: 40% (24 to 58)3 years: 57% (29 to 83)3 years: 28% (9 to 51)

Philippe-Chomettte 20122 years: 51.4% (23.2 to 79.6)Not reportedNot reported

Individual cases data (HDCT & autologous HSCT only)

50 studies2 years: 50.6% (38.7 to 62.5)

3 years: 36.7 (24.4 to 49.0)

5 years: 29.9 (16.7 to 43.1)
Not reportedNot reported

 Some estimates were deduced from Kaplan-Meier plot.
Bisogno 2010: 1 of 14 patients was reported to have achieved complete response before HDCT
Blay 2000: all patients in subgroup N = 24, patients that achieved complete remission before HDCT N = 8, patients that did not achieve complete remission before HDCT N =16
Bui-Nguyen 2012: all patients N = 38 vs. N = 45, patients that achieved complete remission before HDCT N = 20 vs. N 19
Cook 2012: all patients N = 36, patients that achieved complete remission before HDCT N = 13, patients that did not achieve complete remission before HDCT N =18
Abbreviation: CI: confidence interval; HDCT: high-dose chemotherapy; HR: hazard ratio; HSCT: hematopoietic stem cell transplantation; OS: overall survival; SDCT: standard-dose chemotherapy
 
Table 7. Overall survival: Individual cases data

StudyDiagnosisOverall survival(*), 0 = alive,

1= dead
Follow up(**), months

Al Balushi 2009DSRCT072

DSRCT024

DSRCT018

Andres 2006DSRCT010

Bernbeck 2007SYN1

SYN0

Bley 2004LPS07

Boelke 2005MFH089

Buerk 2010ANG01

Cole 1999SYN06

Doros 2008DSRCT10

Engelhardt 2007LPS0

LPS1

LPS0

ANA1

ANA1

ANA0

ANA0

ANA1

LMS0

LMS1

LMS1

LMS1

SYN0

SYN1

SYN1

SYN1

SYN1

MFH0

FIB1

FIB1

ANG0

ANG1

MHP1

Etienne-Mastroianni 2002LMS078

Farruggia 2008SYN036

Fetscher 1996LMS0

Fetscher 1997LMS036

Fraser 2006DSRCT0

DSRCT0

DSRCT0

DSRCT0

Garrido 1998LPS0

Hara 2010ANG167

Hoogerbrugge 1997FIB18

Houet 2010DSRCT0120

Jordan 2010SYN18

MHP129

ANG16

EPI17

EPI16

LMS13

SCS115

Kasper 2007LPS111

MFH06

LPS054

SYN10

SYN114

SYN119

LMS126

LMS14

SYN14

SYN116

LMS02

Kasper 2010SYN122

MFH127

LMS033

MFH112

Kozuka 2002MFH132

MHP023

Kurre 2000DSRCT026

DSRCT042

Kushner 2008DSRCT048

Kushner 2001DSRCT08

Kushner 1996DSRCT023

DSRCT121

DSRCT013

DSRCT034

Lafay-Cousin 2000DSRCT18

DSRCT131

Lashkari 2009MFH099

Lippe 2003DSRCT134

Livaditi 2006DSRCT115

DSRCT111

Madigan 2007RHA0104

Mazuryk 1998DSRCT019

Mingo 2005DSRCT136

Mitchell 1994ANG06

Navid 2006DSRCT13

DSRCT115

Patel 2004MFH0

MFH1

MFH1

MFH1

MFH1

MFH1

Recchia 2006MFH148

Saab 2007DSRCT116

DSRCT12

DSRCT14

DSRCT017

Sung 2003MFH019

CCS045

Watanabe 2006RHA036

Yamamura 2002MFH160

Yonemoto 1999SYN16

SYN16

SYN08

Total: 42 studiesPatients: 108Alive: 49

Dead: 59
FU reported: 71

 (*) Overall survival is dichotomized in alive (0) vs. dead (1) at follow up. Alive includes outcomes such as no evidence of disease, alive with disease, and alive with no further information about disease status. Dead includes outcomes such as died of diseasae, died of complications, and died with not further information of the cause of death. 45% (49 of 108) patients were reported as alive after a wide range of follow up time. This proportion remained 46% (33 of 71) after limiting to patients with follow up data.
(**) Follow up was reported for 66% (71 of 108) patients and varied between 0 and 108 months after the period between diagnosis and beginning of HDCT. The time to event data of these 71 patients were used in a Kaplan Meier survival analysis. For 34% (37 of 108) patients, follow up was not reported and the data of those 37 patients could not be included in the survival analysis.
Abbreviation: FU: follow-up; OS: overall survival
Diagnoses: ANA: anaplastic soft tissue sarcoma; ANG: angiosarcoma; CCS: clear cell sarcoma; DSRCT: desmoplastic small round-cell tumor; EPI: epitheloid sarcoma; FIB: fibrosarcoma; HAP: hemangiopericytoma; LIP: liposarcoma; LMS: leiomyosarcoma; MES: mesenchymal sarcoma; MFH: malignant fibrous histiocytoma; MHP: malignant hemangioperiocytoma; RHA: rhabdoid sarcoma; SCS: spindle cell sarcoma; SYN: synovial sarcoma
 
Table 8. Treatment-related mortality (TRM)

StudyEvents (N)Cause of death

Aggregate comparative data (HDCT & autologous HSCT vs. SDCT)

Bui-Nguyen 20121Treatment-related leukemia death 2 years after HDCT

Aggregate case series data (HDCT & autologous HSCT only)

Bertuzzi 20030

Bisogno 20100

Blay 20001Sudden toxic death of unknown cause at day 29

Cook 20122Not specified

Philippe-Chomettte 20121Died of treatment toxicity 12 months after HDCT

Individual cases data (HDCT & autologous HSCT only)

Doros 20081Not specified

Engelhardt 20073Sepsis, sepsis, pulmonary metastases

Kasper 20071Cardiac arrest of unknown origin

Navid 20061Hepatic and renal failure

Saab 20072Acute myocardial infarction, veno-occlusive disease

Slease 19882Staphylococcus sepsis, progressive encephalopathy

Sum in 12 studies15

 Blay 2000: The authors did not specify, whether the patient was among the 24 patients with adult-type sarcomas or among the 6 patients with rhabdomyosarcoma and Ewing's sarcoma both of which are not included in the present review.
Cook 2012: 1 death within 100 days
 
Table 9. Disease-free survival (DFS)

StudyDisease-free survival, % (95% CI)

Total assessedComplete response before the time of HSCTNot complete response before the time of HSCTT

Aggregate case series data (HDCT & autologous HSCT only)

Cook 20123 years: 23% (10 to 39)3 years: 40% (15 to 69)3 years: 9% (0 to 29)

 Cook 2012: all patients N = 36, patients that achieved complete remission before HDCT N = 13, patients that did not achieve complete remission before HDCT N =18
Abbreviation: CI: confidence interval; HDCT: high-dose chemotherapy; HSCT: hematopoietic stem cell transplantation; DFS: disease-free survival
 
Table 10. Progression-free survival (PFS)

StudyProgression-free survival (95% CI)

Total assessedComplete response before the time of HSCTNot complete response before the time of HSCT

Aggregate comparative data (HDCT & autologous HSCT vs. SDCT)

Bui-Nguyen 20123 years: 9.3% vs. 21.6%, HR 1.34 (0.81 to 2.20, P = 0.25)3 years: 20.0% vs. 62.3%, HR 2.87, (1.3 to 6.3, P = 0.009)Not reported

Aggregate case series data (HDCT & autologous HSCT only)

Bertuzzi 20032 years: 0%Not reportedNot reported

Bisogno 20102 years: 23%

3 years: 15.5%
Not reportedNot reported

Blay 2000Not reported2 years: 62%

5 years: 62%
2 years: 5%

5 years: 5%

Bokemeyer 1997Median 8 months (range 2 to 19)Not reportedNot reported

 Some estimates were deduced from Kaplan-Meier plot. Disease-free survival (DFS), event-free survival (EFS), failure-free survival (FFS), or health-related quality of life (HRQL) not reported.
Bisogno 2010: Definition of endpoint: "For event-free survival (EFS), the interval between diagnosis and the date of latest follow-up, relapse or death was considered." In figure 1 of the article, the endpoint was designated as progression-free survival, which also is meaningful regarding the definition.
(*) Blay 2000: including 5 patients with rhabdomyosarcoma and 1 patient with primitive neuroectodermal tumor
Abbreviation: CI: confidence interval; HDCT: high-dose chemotherapy; HR: hazard ratio; HSCT: hematopoietic stem cell transplantation; PFS: progression-free survival; SDCT: standard-dose chemotherapy
 
Table 11. Non-hematological toxicity grade 3 to 4

StudyNon-hematological toxicity (N)Notice

NauseaMucositisKidneyLiverNervHeartOther

Aggregate comparative data (HDCT & autologous HSCT only)

Bui-Nguyen 2012343Other: 2 infection, 1 pain

Aggregate case series data (HDCT & autologous HSCT only)



Bisogno 20101No grade IV organ dysfunctions

Blay 20008510

Bokemeyer 19972211Nerv: central neurotoxicity; Other: septic episode

Individual cases data (HDCT & autologous HSCT only)



Garrido 19981Neuroleptic malignant syndrome

Kozuka 20021

Kushner 20011

Patel 2004111Other: respiratory distress

Yonemoto 19991

Sum1278240538 events in 105 patients of 9 studies

 Single-arm studies, only transplanted patients. Mucositis not included.
Toxicity defined by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE), NCI 2009b.
 
Table 12. Secondary neoplasia

StudyEventsDiagnosis

Individual cases data (HDCT & autologous HSCT only)

Yamamura 20031Chronic myelogenous leukemia

 Single-arm studies, only transplanted patients.