• leukemia diagnosis;
  • lymphoma diagnosis;
  • myelodysplasia;
  • multiple myeloma;
  • lymphoproliferative disorder


  1. Top of page
  2. Abstract

The clinical indications for diagnostic flow cytometry studies are an evolving consensus, as the knowledge of antigenic definition of hematolymphoid malignancies and the prognostic significance of antigen expression evolves. Additionally the standard of care is not routinely communicated to practicing clinicians and diagnostic services, especially as may relate to new technologies. Accordingly there is often uncertainty on the part of clinicians, payers of medical services, diagnostic physicians and scientists as to the appropriate use of diagnostic flow cytometry. In an attempt to communicate contemporary diagnostic utility of immunophenotypic flow cytometry in the diagnosis and follow-up of patients with hematolymphoid malignancies, the Clinical Cytometry Society organized a two day meeting of international experts in this area to reach a consensus as to this diagnostic tool. This report summarizes the appropriate use of diagnostic flow cytometry as determined by unanimous approval of these experienced practitioners. © 2007 Clinical Cytometry Society

Flow cytometric immunophenotyping (FCI) first appeared in clinical laboratories in the 1980s, in the wake of the AIDS epidemic. Initially utilized to assess CD4 T-cells, the technique was soon applied to lymphoid and eventually myeloid neoplasms. The intervening years have seen a marked rise in the utility of the technique, accompanied by improvements in technology that have enhanced the speed, specificity, and sensitivity. Despite its widespread use and in part, because the technique is so versatile and robust, it continues to suffer from a reputation for inconsistency due to a lack of strict standardization and variability in interpretative experience by its practitioners.

By 1995, practitioners recognized a clear need for consensus statements regarding the indications for FCI, and a group of U.S. and Canadian hematopathologists, hematologists, and laboratory scientists met in Bethesda, MD, on November 16–17, 1995. A series of consensus recommendations was generated by the group that addressed in detail a number of topics, including standardization and validation of laboratory procedures (1), selection of antibody combinations (2), data analysis and interpretation (3), data reporting (4), and medical indications (5). The last reference addressed medical indications largely from disease-specific perspective and did not necessarily identify those clinical signs and symptoms, which led to evaluation for those diseases in the first place. A subsequent consensus document generated by North American and European experts at ISAC 2000 summarized opinions regarding utility of various antibodies to diagnose various diseases (6), but once again neglected to consider the practical situation confronted by clinicians and laboratories: under what clinical circumstances is FCI appropriate? That is, what are the signs and symptoms most likely to prompt FCI and to yield clinically useful data? Conversely, what are the signs and symptoms that do not warrant FCI?

Partly in order to address this significant omission in the literature, a consensus conference was convened at the National Institutes of Health in Bethesda, MD, on July 14–15, 2006. Participating experts were primarily from North America and Europe (see Introduction). Participants were specifically asked to identify those signs and symptoms typically noted in patients with suspected hematolymphoid neoplasms and distinguish among those that do warrant FCI and those that do not warrant FCI. Note that a large and expanding literature documenting typical immunophenotypes of various diseases already exists (7, 8), and the present document makes no attempt to address this topic. Similarly, this document does not address the relative merits of other diagnostic modalities such as microscopic examination, immunohistochemistry, or cytogenetic and molecular studies.


  1. Top of page
  2. Abstract

Hematolymphoid malignancies are typically systemic diseases, with tumor involving more than one tissue site simultaneously. Bone marrow is often affected and resulting cytopenias may bring the patient to the attention of a physician. Some neoplasms elaborate cytokines and the resulting cytopenias, cytoses, and constitutional symptoms such as fever or weight loss may prompt investigation for a hematolymphoid neoplasm. Significant infiltration of tissues by neoplastic cells may present as mass lesions such as lymphadenopathy or organomegaly, lytic lesions of bone, or diffuse lesions such as skin rash or effusions. Infiltration may compromise the function of vital organs such as liver and brain. Clinical disease presentations are highly variable. For example, a patient with acute myeloid leukemia may present with bruising due to thrombocytopenia or with a skin rash due to leukemic infiltration. Furthermore, none of these findings is specific for acute myeloid leukemia, and in each instance the clinician and pathologist must consider a differential diagnosis that includes other hematolymphoid neoplasms, nonhematolymphoid neoplasms, and nonneoplastic etiologies.

Consensus was reached on a list of clinical indications which support FCI. In each instance it is assumed that a hematolymphoid neoplasm is suspected based on clinical or pathological findings and other causes for the abnormality (e.g., nutritional deficiency, infection, drug reaction, or autoimmunity) have been considered. Importantly, the association of the findings listed later with constitutional symptoms increases the likelihood of hematolymphoid neoplasia and strengthens the indication for FCI testing.


Any hematolymphoid neoplasia can present with anemia, leukopenia, and/or thrombocytopenia. In addition, monocytopenia may be a sign of specific hematolymphoid neoplasms. FCI may therefore be indicated in these situations (9–23). Since isolated cytopenias, particularly anemia, commonly occur in nonneoplastic diseases, these alone should not automatically trigger FCI. Pancytopenia is more likely to be associated with neoplasia and FCI is indicated. Because any hematolymphoid neoplasia can produce cytopenia, all lineages should be evaluated.

Elevated Leukocyte Count

Elevated leukocyte counts can be a sign of hematolymphoid neoplasia. The differential diagnosis of a lymphocytosis includes reactive conditions, chronic lymphocytic leukemia (CLL), and other neoplastic disorders of lymphocytes. A specific diagnosis of many chronic lymphoproliferative disorders can be made by flow cytometry (24–47). Monocytosis may be seen with chronic myelomonocytic leukemia or occasionally with other myeloproliferative disorders, and FCI may be helpful in distinguishing these from reactive monocytoses (11, 15, 16, 21, 23, 48). Finally, eosinophilia can be one of the first indications of acute myelogenous leukemia, mastocytosis, acute lymphoblastic leukemia, and T-cell lymphoproliferative disorders (7, 49–54). Neutrophilic leukocytosis is, in general, not an indication for flow cytometry in the absence of blasts, except for focused assays, such as CD64 expression, that provide objective evidence of a systemic acute inflammatory response to infection or sepsis (55, 56).

Isolated findings of polycythemia, thrombosis, or basophilia are not sufficient to warrant FCI, as they are more commonly associated with nonmalignant diseases or hematolymphoid neoplasms lacking characteristic FCI findings.

Observation of Atypical Cells or Blasts and Evaluation of Body Fluids

Identification of blasts in the marrow or peripheral blood is an absolute indication for flow cytometry. (21, 57–97). FCI confirms that atypical cells are blasts and plays an important role in the diagnosis and classification of acute leukemia. FCI is indicated in the evaluation of atypical mononuclear cells in body fluids to rule out reactive activated lymphoid cells and detect possible neoplasia (98–100) due to its greater sensitivity and specificity than morphology alone (101–103). Specifically, FCI is indicated in the evaluation of serous effusions and CSF, including aqueous or vitreous humor of patients with a history of hematolymphoid neoplasia (104–106).

Plasmacytosis or Monoclonal Gammopathy

These findings may be seen in plasma cell dyscrasias or multiple myeloma, characteristically associated with clonal proliferations of plasma cells, often with aberrant phenotypes. Monoclonal gammopathies can also be seen in chronic B lymphoproliferative disorders that can be diagnosed and often classified by FCI (5, 24, 107, 108). FCI assists in the differential diagnosis between plasma cell myeloma and monoclonal gammopathies of undetermined significance by determining the percentage of aberrant or clonal plasma cells of all bone marrow plasma cells (108–114) (Rawstron A, Orfao A, Mateo G. Report of the EMN (European Myeloma Network) workshop on flow cytometry in multiple myeloma and related disorders, to be submitted). FCI is useful in diagnostic evaluation of unexplained marrow plasmacytosis by assessing phenotypically aberrant or clonal plasma cells and its ability to detect other underlying monoclonal B-cell process (5, 108).

Organomegaly and Tissue Masses

Tissue-based lymphoid neoplasias commonly affect lymph nodes, spleen, mucosa-associated lymphoid tissue, skin, or nonlymphoid solid organs resulting in masses or organomegaly. With the exception of Hodgkin's lymphoma, FCI is extremely useful in the diagnosis and subclassification of tissue-based lymphoid neoplasias, and there is consensus that this testing is indicated in lymphadenopathy (46, 107, 115–126) (also see references24–47 for lymphocytosis), organomegaly (including but not limited to splenomegaly and hepatomegaly) (127), and tissue infiltrates (including but not limited to skin, mucosal sites, and bone) (34, 36, 39, 42, 124, 128–130). Recent work suggests that with careful assessment it is possible to make a diagnosis of classical Hodgkin's lymphoma by FCI (131), but the necessary procedures are not currently employed in most laboratories.

Patient Monitoring Indications

Once an initial diagnosis of hematolymphoid neoplasm is rendered, additional FCI may be performed. Indications for testing in this setting are as follows:

  • Staging disease to document the extent of involvement (111, 132, 133). Although flow cytometry is more sensitive than conventional morphology for detecting disease in bone marrow and blood, clinical decisions based on upstaging due to detection of submicroscopic disease should be carefully considered because in many diseases the significance of staging using more sensitive technology has not been well established. The value of performing flow cytometric staging on both bilateral marrow aspirates, compared to pooled specimens from both sides, has not been established, though in the case of minimal residual disease analysis studying two independent marrow samples does not provide significant additional information (134).

  • Detecting potential therapeutic targets, e.g., CD20, CD52 (135, 136).

  • Assessment of response to therapy (including “minimal residual disease” testing) and persistence of FCI-detectable MRD following therapy, which is often an adverse prognostic factor. However, the optimal frequency of such monitoring has not been established (112, 137–163).

  • Documentation of progression or relapse.

  • Diagnosis of additional intercurrent hematolymphoid neoplasm, either treatment- related (such as MDS/AML or PTLD) or coincidental (164–170).

  • Evaluation of disease acceleration (e.g., CML blast crisis) or transformation (e.g., diffuse large B cell lymphoma in low grade lymphoma or CLL) (66, 74, 96, 171, 172).

  • Prognostication, especially in CLL, with detection of ZAP70 or CD38 (135, 136, 173–179), acute leukemia (59, 77, 78, 180–185), or myeloma, whereby phenotype, presence of circulating plasma cells, or assessment of proliferation rate can predict progression (111, 114, 186–188).

Samples submitted for FCI may not also not show hematolymphoid neoplasia. Some patients, despite highly suspicious signs and symptoms of hematolymphoid neoplasm, will have another cancer type, or a nonneoplastic condition such as an occult infection or autoimmune process. Samples from patients with a hematolymphoid neoplasm may not be involved and/or therapy may reduce the disease burden to undetectable levels. In such cases, a negative evaluation for hematolymphoid neoplasm by FCI may still be informative (25, 35, 44, 48, 122). Of course, the extent to which a negative FCI study is valuable is related in part to the quality of the evaluation, which is dependent on the antibody panel; specifically which antibodies, how many, and in what combinations (reference Technical consensus document, Wood et al., 2007).

Flow cytometry is generally not indicated in the following conditions because they are usually not associated with hematolymphoid malignancy or associated with hematolymphoid neoplasms that are not detectable by FCI.

  • Mature neutrophilia

  • Polyclonal hypergammaglobulinemia

  • Polycythemia

  • Thrombocytosis

  • Basophilia


  1. Top of page
  2. Abstract

Flow cytometry is diagnostically productive and cost-effective. Therefore, flow cytometric studies are an integral component of contemporary hematopathology practice. Knowledge of the flow cytometric findings of the hematopoietic cells involved in hematolymphoid neoplasms is critical in patient management, providing data that aids in diagnosis, staging, prognosis, therapeutic targets, and disease monitoring. FCI, however, is not indicated in all clinical situations and these consensus guidelines are meant to aid decisions on the use of flow cytometry. We present guidelines for appropriate clinical settings for flow cytometric testing for hematolymphoid neoplasia developed by an international panel of experts. Previous consensus recommendations (5, 6) utilized a disease-oriented approach which, while informative, tended to obscure the practical aspects of best practice in the setting of a flow cytometry laboratory. The current consensus document was developed as a practical guide to FCI based on clinical settings that confront clinicians and laboratories. Although this is the first consensus document to explicitly summarize the clinical signs and symptoms that warrant the use of FCI, it in fact reflects clinical practice exercised since the inception of the technique.

The biologic analyses of neoplasms outpace personalized treatment options. Indeed, FCI provides an important tool for the development or selection of personalized treatment and stimulates the development of new strategies. However, the clinical application of the biologic information provided by flow cytometric analyses must be evaluated in large, well designed, clinical trials. Furthermore, future clinical trials to evaluate novel therapeutic regimens must consider the usefulness of flow cytometric data and other biologic parameters. Consequently, the contribution of flow cytometry to patient care is a dynamic and evolving process with important clinical applications. Thus periodic review and assessment of medical indications for flow cytometric evaluation is necessary to keep pace with scientific and clinical advancements.


  1. Top of page
  2. Abstract
  • 1
    Stelzer GT,Marti G,Hurley A,McCoy PJr,Lovett EJ,Schwartz A. U.S.-Canadian Consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: standardization and validation of laboratory procedures. Cytometry 1997; 30(5): 214230.
  • 2
    Stewart CC,Behm FG,Carey JL,Cornbleet J,Duque RE,Hudnall SD,Hurtubise PE,Loken M,Tubbs RR,Wormsley S. U.S.-Canadian Consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: selection of antibody combinations. Cytometry 1997; 30(5): 231235.
  • 3
    Borowitz MJ,Bray R,Gascoyne R,Melnick S,Parker JW,Picker L,Stetler-Stevenson M. U.S.-Canadian Consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: data analysis and interpretation. Cytometry 1997; 30(5): 236244.
  • 4
    Braylan RC,Atwater SK,Diamond L,Hassett JM,Johnson M,Kidd PG,Leith C,Nguyen D. U.S.-Canadian Consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: data reporting. Cytometry 1997; 30(5): 245248.
  • 5
    Davis BH,Foucar K,Szczarkowski W,Ball E,Witzig T,Foon KA,Wells D,Kotylo P,Johnson R,Hanson C, and others. U.S.-Canadian Consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: medical indications. Cytometry 1997; 30(5): 249263.
  • 6
    Braylan RC,Orfao A,Borowitz MJ,Davis BH. Optimal number of reagents required to evaluate hematolymphoid neoplasias: results of an international consensus meeting. Cytometry 2001; 46(1): 2327.
  • 7
    Jaffe E,Harris N,Stein H,Vardiman J. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues Lyon: IARC Press; 2001.
  • 8
    Jennings C,Foon K. Recent advances in flow cytometry: application to the diagnosis of hematologic malignancy. Blood 1997; 90(8): 28632892.
  • 9
    Arroyo J,Fernandez M,Hernandez J,Orfao A,San Miguel J,Canizo M. Impact of immunophenotype on prognosis of patients with myelodysplastic syndromes. Its value in patients without karyotypic abnormalities. Hematol J 2004; 5(3): 227233.
  • 10
    Bargetzi MJ,Wortelboer M. Severe neutropenia in T-large granular lymphocyte leukemia corrected by intensive immunosuppression. Ann Hematol 1996; 73(3): 149151.
  • 11
    Benesch M,Deeg HJ. Flow cytometry for diagnosis and assessment of prognosis in patients with myelodysplastic syndromes. Hematology 2004; 9(3): 171177.
  • 12
    Bible K,Ca AT. Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis. Br J Haematol 1996; 93(2): 406408.
  • 13
    Burks EJ,Loughran TPJr. Pathogenesis of neutropenia in large granular lymphocyte leukemia and Felty syndrome. Blood Rev 2006; 20(5): 245266.
  • 14
    Cherian S,Moore J,Bantly A,Vergilio J,Klein P,Luger S,Bagg A. Flow-cytometric analysis of peripheral blood neutrophils: a simple, objective, independent and potentially clinically useful assay to facilitate the diagnosis of myelodysplastic syndromes. Am J Hematol 2005; 79(3): 243245.
  • 15
    Cherian S,Moore J,Bantly A,Vergilio J,Klein P,Luger S,Bagg A. Peripheral blood MDS score: a new flow cytometric tool for the diagnosis of myelodysplastic syndromes. Cytometry B Clin Cytom 2005; 64B(1): 917.
  • 16
    Kussick S,Wood B. Using 4-color flow cytometry to identify abnormal myeloid populations. Arch Pathol Lab Med 2003; 127(9): 11401147.
  • 17
    Kwong Y,La KFW. Association of pure red cell aplasia with T large granular lymphocyte leukaemia. J Clin Pathol 1998; 51(9): 672675.
  • 18
    Maynadie M,Picard F. Immunophenotypic clustering of myelodysplastic syndromes. Blood 2002; 100(7): 23492356.
  • 19
    Pastor E,Sayas M. Severe neutropenia associated with large granular lymphocyte lymphocytosis: successful control with cyclosporin A. Blut 1989; 59(6): 501502.
  • 20
    Sood R,Stewart CC. Neutropenia associated with T-cell large granular lymphocyte leukemia: long-term response to cyclosporine therapy despite persistence of abnormal cells. Blood 1998; 91(9): 33723378.
  • 21
    Stetler-Stevenson M,Arthur DC,Jabbour N,Xie XY,Molldrem J,Barrett AJ,Venzon D,Rick ME. Diagnostic utility of flow cytometric immunophenotyping in myelodysplastic syndrome. Blood 2001; 98(4): 979987.
  • 22
    Wells DA,Hall MC. Occult B cell malignancies can be detected by three-color flow cytometry in patients with cytopenias. Leukemia 1998; 12(12): 20152023.
  • 23
    Wells DA,Benesch M. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood 2003; 102(1): 394403.
  • 24
    Ahmad E,Garcia C,Davis B. Clinical utility of CD23 and FMC-7 antigen coexistent expression in B-cell lymphoproliferative disorder subclassification. Cytometry 2002; 50: 17.
  • 25
    Brown K. Nonmalignant disorders of lymphocytes. Clin Lab Sci 1997; 10: 329335.
  • 26
    Cheson BD,Bennett JM,Grever M,Kay N,Keating MJ,O'Brien S,Rai KR. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87(12): 49904997.
  • 27
    Cro L,Guffanti A,Colombi M,Cesana B,Grimoldi MG,Patriarca C,Goldaniga M,Neri A ID,Cortelezzi A,Maiolo AT,Baldini L. Diagnostic role and prognostic significance of a simplified immunophenotypic classification of mature B cell chronic lymphoid leukemias. Leukemia 2003; 17(1): 125132.
  • 28
    Dahmoush L,Hijazi Y,Barnes E,Stetler-Stevenson M,Abati A. Adult T-cell leukemia/lymphoma: a cytopathologic, immunocytochemical, and flow cytometric study. Cancer 2002; 96(2): 110116.
  • 29
    DiGiuseppe J,Borowitz M. Clinical utility of flow cytometry in the chronic lymphoid leukemias. Semin Oncol 1998; 25(1): 610.
  • 30
    Frater J,McCarron K,Hammel J,Shapiro J,Miller M,Tubbs R,Pettay J,Hsi E. Typical and atypical chronic lymphocytic leukemia differ clinically and immunophenotypically. Am J Clin Pathol 2001; 116: 655664.
  • 31
    Geisler C,Larsen J,Hansen N,Hansen M,Christensen B,Lund B,Nielsen H,Plesner T,Thorling K,Andersen E. Prognostic importance of flow cytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia. Blood 1991; 78(7): 17951802.
  • 32
    Gorczyca W,Weisberger J,Liu Z,Tsang P,Hossein M,Wu C,Dong H,Wong J,Tugulea S,Dee S, and others. An approach to diagnosis of T-cell lymphoproliferative disorders by flow cytometry. Cytometry 2002; 50(3): 177190.
  • 33
    Hudnall S,Pael J,Schwab H,Martinez J. Comparative immunophenotypic features of EBV-positive and EBV-negative atypical lymphocytosis. Cytometry B Clin Cytom 2003; 55B: 2228.
  • 34
    Jones D,Dang N,Duvic M,Washington L,Huh Y. Absence of CD26 expression is a useful marker for diagnosis of T-cell lymphoma in peripheral blood. Am J Clin Pathol 2001; 115(6): 885892.
  • 35
    Karandikar N,Hotchkiss E,Mckenna R,Kroft S. Transient stress lymphocytosis: an immunophenotypic characterization of the most common cause of newly identified adult lymphocytosis in a tertiary hospital. Am J Clin Pathol 2002; 116(3): 662666.
  • 36
    Langerak A,van Den Beemd R,Wolvers-Tettero I,Boor P,van Lochem E,Hooijkaas H,van Dongen J. Molecular and flow cytometric analysis of the Vbeta repertoire for clonality assessment in mature TCRalphabeta T-cell proliferations. Blood 2001; 98(1): 165173.
  • 37
    Marti GE,Rawstron AC. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol 2005; 130(3): 325332.
  • 38
    Matutes E,Owusu-Ankomah K,Morilla R,Garcia M,Houlihan A,Que T,Catovsky D. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 1994; 8(10): 16401645.
  • 39
    Morice W,Katzmann J,Pittelkow M,el-Azhary R,Gibson L,Hanson C. A comparison of morphologic features, flow cytometry, TCR-Vbeta analysis, and TCR-PCR in qualitative and quantitative assessment of peripheral blood involvement by Sezary syndrome. Am J Clin Pathol 2006; 125(3): 364374.
  • 40
    Nelson B,Variakojis D,Peterson L. Leukemic phase of B-cell lymphomas mimicking chronic lymphocytic leukemia and variants at presentation. Mod Pathol 2002; 15(11): 11111120.
  • 41
    Rawstron A. Prevalence and characteristics of monoclonal B-cell lymphocytosis (MBL) in healthy individuals and the relationship with clinical disease. J Biol Regul Homeost Agents 2004; 18(2): 155160.
  • 42
    Rawstron A,Green M,Kuzmicki A,Kennedy B,Fenton J,Evans P,O'Connor S,Richards S,Morgan G,Jack A, and others. Monoclonal B lymphocytes with the characteristics of “indolent” chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts. Blood 2002; 100(2): 635639.
  • 43
    Rose M,Berliner N. T-cell large granular lymphocyte leukemia and related disorders. Oncologist 2004; 9(3): 247258.
  • 44
    Salcedo I,Campos-Caro A,Sampalo A,Reales E,Brieva J. Persistent polyclonal B lymphocytosis: an expansion of cells showing IgVH gene mutations and phenotypic features of normal lymphocytes from the CD27+ marginal zone B-cell compartment. Br J Haematol 2002; 116(3): 662666.
  • 45
    Schlette E,Bueso-Ramos C,Giles F,Glassman A,Hayes K,Medeiros L. Mature B-cell leukemias with more than 55% prolymphocytes. A heterogeneous group that includes an unusual variant of mantle cell lymphoma. Am J Clin Pathol 2001; 115(4): 571581.
  • 46
    Tworek J,Singleton T,Schnitzer B,Hsi E,Ross C. Flow cytometric and immunohistochemical analysis of small lymphocytic lymphoma, mantle cell lymphoma, and plasmacytoid small lymphocytic lymphoma. Am J Clin Pathol 1998; 110(5): 582589.
  • 47
    Wang C,Amato D,Rabah R,Zheng J,Fernandes B. Differentiation of monoclonal B lymphocytosis of undetermined significance (MLUS) and chronic lymphocytic leukemia (CLL) with weak CD5 expression from CD5(-) CLL. Leuk Res 2002; 26(12): 11251129.
  • 48
    Xu Y,McKenna RW. Flow cytometric analysis of monocytes as a tool for distinguishing chronic myelomonocytic leukemia from reactive monocytosis. Am J Clin Pathol 2005; 124(5): 799806.
  • 49
    Abruzzo LV,Jaffe ES,Cotelingam JD,Whang-Peng J,Del Duca VJr,Medeiros LJ. T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. Am J Surg Pathol 1992; 16(3): 236245.
  • 50
    Berki T,David M,Bone B,Losonczy H,Vass J,Nemeth P. New diagnostic tool for differentiation of idiopathic hypereosinophilic syndrome (HES) and secondary eosinophilic states. Pathol Oncol Res 2001; 7(4): 292297.
  • 51
    Catovsky D,Bernasconi C,Verdonck PJ,Postma A,Hows J,van der Does-van den Berg A,Rees JK,Castelli G,Morra E,Galton DA. The association of eosinophilia with lymphoblastic leukaemia or lymphoma: a study of seven patients. Br J Haematol 1980; 45(4): 523534.
  • 52
    Gallamini A,Carbone A,Lista P,Cavallero G,Reato G,Fruttero A,Novero D,Asnaghi G,di Celle PF,Foa R. Intestinal T-cell lymphoma with massive tissue and blood eosinophilia mediated by IL-5. Leuk Lymphoma 1995; 17(1–2): 155161.
  • 53
    Lichtman M,Segel G. Uncommon phenotypes of acute myelogenous leukemia: basophilic, mast cell, eosinophilic, and myeloid dendritic cell subtypes: a review. Blood Cells Mol Dis 2005; 35(3): 370383.
  • 54
    Vaklavas C,Tefferi A,Butterfield J,Ketterling R,Verstovsek S,Kantarjian H,Pardanani A. ‘Idiopathic’ eosinophilia with an Occult T-cell clone: Prevalence and clinical course. Leuk Res 2007; 31(5): 691694.
  • 55
    Davis B. Improved Diagnostic Approaches to Infection/Sepsis Detection. Expert Rev Mol Diag 2005; 5: 193207.
  • 56
    Davis B,Olsen S,Ahmad E,Bigelow N. Neutrophil CD64 is an improved indicator of infection or sepsis in emergency department patients. Arch Pathol Lab Med 2006; 130(5): 654661.
  • 57
    Bene M,Bernier M,Casasnovas R,Castoldi G,Doekharan D,van der Holt B,Knapp W,Lemez P,Ludwig W,Matutes E, and others. Acute myeloid leukaemia M0: haematological, immunophenotypic and cytogenetic characteristics and their prognostic significance: an analysis in 241 patients. Br J Haematol 2001; 113(3): 737745.
  • 58
    Borowitz M,Hunger S,Carroll A,Shuster J,Pullen D,Steuber C,Cleary M. Predictability of the t(1;19)(q23;p13) from surface antigen phenotype: implications for screening cases of childhood acute lymphoblastic leukemia for molecular analysis: a Pediatric Oncology Group study. Blood 1993; 82(4): 10861091.
  • 59
    Borowitz M,Rubnitz J,Nash M,Pullen D,Camitta B. Surface antigen phenotype can predict TEL-AML1 rearrangement in childhood B-precursor ALL: a Pediatric Oncology Group study. Leukemia 1998; 12(11): 17641770.
  • 60
    Brunning R. Classification of acute leukemias. Semin Diagn Pathol 2003; 20(3): 142153.
  • 61
    Casasnovas R,Slimane F,Garand R,Faure G,Campos L,Deneys V,Bernier M,Falkenrodt A,Lecalvez G,Maynadie M, and others. Immunological classification of acute myeloblastic leukemias: relevance to patient outcome. Leukemia 2003; 17(3): 515527.
  • 62
    Cohen P,Hoyer J,Kurtin P,Dewald G,Hanson C. Acute myeloid leukemia with minimal differentiation. A multiple parameter study. Am J Clin Pathol 1998; 109(1): 3238.
  • 63
    D'Arena G,Cascavilla N,Nunziata G,Perla G,Matera R,Carella A. Usefulness of RA and RO isoforms of common leukocyte antigen (CD45) for early distinction between normal and abnormal promyelocytes. Leuk Lymphoma 2002; 43(9): 18231825.
  • 64
    De Zen L,Bicciato S,te Kronnie G,Basso G. Computational analysis of flow-cytometry antigen expression profiles in childhood acute lymphoblastic leukemia: an MLL/AF4 identification. Leukemia 2003; 17(8): 15571565.
  • 65
    De Zen L,Orfao A,Cazzaniga G,Masiero L,Cocito M,Spinelli M,Rivolta A,Biondi A,Zanesco L,Basso G. Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia: correlation with specific genotype. I. ETV6/AML1 ALLs identification. Leukemia 2000; 14(7): 12251231.
  • 66
    Dorfman D,Longtine J,Fox E,Weinberg D,Pinkus G. T-cell blast crisis in chronic myelogenous leukemia. Immunophenotypic and molecular biologic findings. Am J Clin Pathol 1997; 107(2): 168176.
  • 67
    Feuillard J,Jacob M,Valensi F,Maynadie M,Gressin R,Chaperot L,Arnoulet C,Brignole-Baudouin F,Drenou B,Duchayne E, and others. Clinical and biologic features of CD4(+)CD56(+) malignancies. Blood 2002; 99(5): 15561563.
  • 68
    Haferlach T,Kern W,Schnittger S,Schoch C. Modern diagnostics in acute leukemias. Crit Rev Oncol Hematol 2005; 56(2): 223234.
  • 69
    Hrusak O,Porwit-MacDonald A. Antigen expression patterns reflecting genotype of acute leukemias. Leukemia 2002; 16(7): 12331258.
  • 70
    Hurwitz C,Raimondi S,Head D,Krance R,Mirro JJ,Kalwinsky D,Ayers G,Behm F. Distinctive immunophenotypic features of t(8;21)(q22;q22) acute myeloblastic leukemia in children. Blood 1992; 80(12): 31823188.
  • 71
    Jacob M,Chaperot L,Mossuz P,Feuillard J,Valensi F,Leroux D,Bene M,Bensa J,Briere F,Plumas J. CD4+ CD56+ lineage negative malignancies: a new entity developed from malignant early plasmacytoid dendritic cells. Haematologica 2003; 88(8): 941955.
  • 72
    Kaleem Z,Crawford E,Pathan M,Jasper L,Covinsky M,Johnson L,White G. Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data. Arch Pathol Lab Med 2003; 127(1): 4248.
  • 73
    Kaleem Z,White G. Diagnostic criteria for minimally differentiated acute myeloid leukemia (AML-M0). Evaluation and a proposal. Am J Clin Pathol 2001; 115(6): 876884.
  • 74
    Khalidi H,Brynes R,Medeiros L,Chang K,Slovak M,Snyder D,Arber D. The immunophenotype of blast transformation of chronic myelogenous leukemia: a high frequency of mixed lineage phenotype in “lymphoid” blasts and A comparison of morphologic, immunophenotypic, and molecular findings. Mod Pathol 1998; 11(12): 12111221.
  • 75
    Kroft S. Role of flow cytometry in pediatric hematopathology. Am J Clin Pathol 2004; 122 ( Suppl): S1932.
  • 76
    Lai R,Hirsch-Ginsberg C,Bueso-Ramos C. Pathologic diagnosis of acute lymphocytic leukemia. Hematol Oncol Clin North Am 2000; 14(6): 12091235.
  • 77
    Langebrake C,Creutzig U,Reinhardt D. Immunophenotype of Down syndrome acute myeloid leukemia and transient myeloproliferative disease differs significantly from other diseases with morphologically identical or similar blasts. Klin Padiatr 2005; 217(3): 126134.
  • 78
    Legrand O,Perrot J,Simonin G,Baudard M,Cadiou M,Blanc C,Ramond S,Viguie F,Marie J,Zittoun R. Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression. Br J Haematol 1998; 100(1): 147155.
  • 79
    Lichtman MA,Segel GB. Uncommon phenotypes of acute myelogenous leukemia: basophilic, mast cell, eosinophilic, and myeloid dendritic cell subtypes: a review. Blood Cells Mol Dis 2005; 35(3): 370383.
  • 80
    Melnick S. Acute lymphoblastic leukemia. Clin Lab Med 1999; 19(1): 169186.
  • 81
    Munoz L,Aventin A,Villamor N,Junca J,Acebedo G,Domingo A,Rozman M,Torres J,Tormo M,Nomdedeu J. Immunophenotypic findings in acute myeloid leukemia with FLT3 internal tandem duplication. Haematologica 2003; 88(6): 637645.
  • 82
    Ogata K,Kishikawa Y,Satoh C,Tamura H,Dan K,Hayashi A. Diagnostic application of flow cytometric characteristics of CD34+ cells in low-grade myelodysplastic syndromes. Blood 2006; 108(3): 10371044.
  • 83
    Orfao A,Chillon M,Bortoluci A,Lopez-Berges M,Garcia-Sanz R,Gonzalez M,Tabernero M,Garcia-Marcos M,Rasillo A,Hernandez-Rivas J, and others. The flow cytometric pattern of CD34, CD15 and CD13 expression in acute myeloblastic leukemia is highly characteristic of the presence of PML-RARA gene rearrangements. Haematologica 1999; 84(5): 405412.
  • 84
    Orfao A,Ortuno F,de Santiago M,Lopez A,San Miguel J. Immunophenotyping of acute leukemias and myelodysplastic syndromes. Cytometry A 2004; 58A(1): 6271.
  • 85
    Paietta E,Racevskis J,Neuberg D,Rowe J,Goldstone A,Wiernik P. Expression of CD25 (interleukin-2 receptor alpha chain) in adult acute lymphoblastic leukemia predicts for the presence of BCR/ABL fusion transcripts: results of a preliminary laboratory analysis of ECOG/MRC Intergroup Study E2993. Eastern Cooperative Oncology Group/Medical Research Council. Leukemia 1997; 11(11): 18871890.
  • 86
    Porwit-MacDonald A,Janossy G,Ivory K,Swirsky D,Peters R,Wheatley K,Walker H,Turker A,Goldstone A,Burnett A. Leukemia-associated changes identified by quantitative flow cytometry. IV. CD34 overexpression in acute myelogenous leukemia M2 with t(8;21). Blood 1996; 87(3): 11621169.
  • 87
    Reichard K,Burks E,Foucar M,Wilson C,Viswanatha D,Hozier J,Larson R. CD4(+) CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells. Am J Surg Pathol 2005; 29(10): 12741283.
  • 88
    Riley R,Massey D,Jackson-Cook C,Idowu M,Romagnoli G. Immunophenotypic analysis of acute lymphocytic leukemia. Hematol Oncol Clin North Am 2002; 16(2): 245299.
  • 89
    Rizzatti E,Portieres F,Martins S,Rego E,Zago M,Falcao R. Microgranular and t(11;17)/PLZF-RARA variants of acute promyelocytic leukemia also present the flow cytometric pattern of CD13, CD34, and CD15 expression characteristic of PML-RARA gene rearrangement. Am J Hematol 2004; 76(1): 4451.
  • 90
    Schwartz S,Rieder H,Schlager B,Burmeister T,Fischer L,Thiel E. Expression of the human homologue of rat NG2 in adult acute lymphoblastic leukemia: close association with MLL rearrangement and a CD10(-)/CD24(-)/CD65s(+)/CD15(+) B-cell phenotype. Leukemia 2003; 17(8): 15891595.
  • 91
    Stasi R,Amadori S. AML-M0: a review of laboratory features and proposal of new diagnostic criteria. Blood Cells Mol Dis 1999; 25(2): 120129.
  • 92
    Sulak L,Clare C,Morale B,Hansen K,Montiel M. Biphenotypic acute leukemia in adults. Am J Clin Pathol 1990; 94(1): 548.
  • 93
    te Kronnie G,Bicciato S,Basso G. Acute leukemia subclassification: a marker protein expression perspective. Hematology 2004; 9(3): 165170.
  • 94
    Todd W. Acute myeloid leukemia and related conditions. Hematol Oncol Clin North Am 2002; 16(2): 301319.
  • 95
    Weir E,Borowitz M. Flow cytometry in the diagnosis of acute leukemia. Semin Hematol 2001; 38(2): 124138.
  • 96
    Williams S,Wellhausen S,Barker R,Janckila A. Acute bilineage leukemia after chronic myelogenous leukemia. J Ky Med Assoc 1997; 95(9): 393396.
  • 97
    Zeleznikova T,Babusikova O. The value of dot plot patterns and leukemia-associated phenotypes in AML diagnosis by multiparameter flow cytometry. Neoplasma 2005; 52(6): 517522.
  • 98
    Ceyhan B,Demiralp E,Celikel T. Analysis of pleural effusions using flow cytometry. Respiration 1996; 63(1): 1724.
  • 99
    Czader M,Ali S. Flow cytometry as an adjunct to cytomorphologic analysis of serous effusions. Diagn Cytopathol 2003; 29(2): 7478.
  • 100
    Stonesifer K,Xiang J,Wilkinson E,Benson N,Braylan R. Flow cytometric analysis and cytopathology of body cavity fluids. Acta Cytol 1987; 31(2): 125130.
  • 101
    Finn W,Peterson L,James C,Goolsby C. Enhanced detection of malignant lymphoma in cerebrospinal fluid by multiparameter flow cytometry. Am J Clin Pathol 1998; 110(3): 341346.
  • 102
    Roma A,Garcia A,Avagnina A,Rescia C,Elsner B. Lymphoid and myeloid neoplasms involving cerebrospinal fluid: comparison of morphologic examination and immunophenotyping by flow cytometry. Diagn Cytopathol 2002; 27(5): 271275.
  • 103
    Subira D,Gorgolas M,Castanon S,Serrano C,Roman A,Rivas F,Tomas J. Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non-Hodgkin's lymphoma in AIDS patients. HIV Med 2005; 6(1): 2126.
  • 104
    Davis J,Viciana A,Ruiz P. Diagnosis of intraocular lymphoma by flow cytometry. Am J Ophthalmol 1997; 124(3): 362372.
  • 105
    Ohta K. [T lymphocyte subsets in aqueous humor from patients with uveitis]. Nippon Ganka Gakkai Zasshi 1996; 100(11): 899904.
  • 106
    Zaldivar R,Martin D,Holden J,Grossniklaus H. Primary intraocular lymphoma: clinical, cytologic, and flow cytometric analysis. Ophthalmology 2004; 111(9): 17621767.
  • 107
    Garcia C,Rooney M,Ahmad E,Davis BH. Diagnostic usefulness of CD23 and FMC-7 antigen expression in B cell lymphoma classification. Amer J Clin Pathol 2001; 115: 258265.
  • 108
    Ocqueteau M,Orfao A,Almeida J,Blade J,Gonzales M,Garcia-Sanz R,Lopez-Berges M,Moro M,Hernandez J,Escribano L and others. Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma. Am J Pathol 1998; 152(6): 16551665.
  • 109
    Kumar S,Kimlinger T,Lust J,Donovan K,Witzig T. Expression of CD52 on plasma cells in plasma cell proliferative disorders. Blood 2003; 102(3): 10751077.
  • 110
    Kumar S,Rajkumar S,Kyle R,Lacy M,Dispenzieri A,Fonseca R,Lust J,Gertz M,Greipp P,Witzig T. Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance. J Clin Oncol 2005; 23(24): 56685674.
  • 111
    Nowakowsi G,Witzig T,Dingli D,Tracz M,Gertz M,Lacy M,Lust J,Dispenzieri A,Greipp P,Kyle R, and others. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 2005; 106(7): 22762279.
  • 112
    Owen R,Rawstron A. Minimal residual disease monitoring in multiple myeloma: flow cytometry is the method of choice. Br J Haematol 2005; 128(5): 732733.
  • 113
    Perez-Andres M,Almeida J,Martin-Ayuso M,Moro M,Martin-Nunez G,Galende J,Borrego D,Rodriguez M,Ortega F,Hernandez J, and others. Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma, and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment. Leukemia 2005; 19: 449455.
  • 114
    Sahara N,Takeshita A,Shigeno K. Clinicopathological and prognostic characteristics of CD56- negative multiple myeloma. British Journal of Hematology 2002; 117: 882885.
  • 115
    Cannon C,Richardson L. Value of flow cytometry in the evaluation of head and neck fine-needle lymphoid aspirates: a 3-year retrospective review of a community-based practice. Otolaryngol Head Neck Surg 2001; 124: 544548.
  • 116
    Chen L,Kuriakose P,Hawley R,Janakiraman N,Maeda K. Hematologic malignancies with primary retroperitoneal presentation: clinicopathologic study of 32 cases. Arch Pathol Lab Med 2005; 129: 655660.
  • 117
    Chen Y,Savargaonkar P,Fuchs A,Wasserman P. Role of flow cytometry in the diagnosis of lymphadenopathy in children. Diagn Cytopathol 2002; 26: 59.
  • 118
    Gong J,Snyder M,Lagoo A,Vollmer R,Dash R,Madden J,Buckley P,Jones C. Diagnostic impact of core-needle biopsy on fine-needle aspiration of non-Hodgkin lymphoma. Diagn Cytopathol 2004; 31: 2330.
  • 119
    Liu K,Stern R,Rogers R,Dodd L,Mann K. Diagnosis of hematopoietic processes by fine-needle aspiration in conjunction with flow cytometry: A review of 127 cases. Diagn Cytopathol 2001; 24: 110.
  • 120
    Mehra M,Tamhane A,Eloubeidi M. EUS-guided FNA combined with flow cytometry in the diagnoses of suspected or recurrent intrathoracic or retroperitoneal lymphoma. Gastrointest Endosc 2005; 62: 508513.
  • 121
    Mourad W,Tulbah A,Shoukri M,Al Dayel F,Akhtar M,Ali M,Hainau B,Martin J. Primary diagnosis and REAL/WHO classification of non-Hodgkin's lymphoma by fine-needle aspiration: cytomorphologic and immunophenotypic approach. Diagn Cytopathol 2003; 28: 191195.
  • 122
    Ravoet C,Demartin S,Gerard R,Dehon M,Peny M,Petit B,Delannoy A,Husson B. Contribution of flow cytometry to the diagnosis of malignant and non malignant conditions in lymph node biopsies. Leuk Lymphoma 2004; 45: 15871593.
  • 123
    Ribeiro A,Vazquez-Sequeiros E,Wiersema L,Wang K,Clain J,Wiersema M. EUS-guided fine-needle aspiration combined with flow cytometry and immunocytochemistry in the diagnosis of lymphoma. Gastrointest Endosc 2001; 53: 485491.
  • 124
    Sigstad E,Dong H,Davidson B,Berner A,Tierens A,Risberg B. The role of flow cytometric immunophenotyping in improving the diagnostic accuracy in referred fine-needle aspiration specimens. Diagn Cytopathol 2004; 31: 159163.
  • 125
    Young N,Al Saleem T,Ehya H,Smith M. Utilization of fine-needle aspiration cytology and flow cytometry in the diagnosis and subclassification of primary and recurrent lymphoma. Cancer 1998; 84: 252261.
  • 126
    Zeppa P,Marino G,Troncone G,Fulciniti F,De Renzo A,Picardi M,Benincasa G,Rotoli B,Vetrani A,Palombini L. Fine-needle cytology and flow cytometry immunophenotyping and subclassification of non-Hodgkin lymphoma: a critical review of 307 cases with technical suggestions. Cancer 2004; 102: 5565.
  • 127
    Eloubeidi M,Varadarajulu S,Eltoum I,Jhala D,Chhieng D,Jhala N. Transgastric Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy and Flow Cytometry of Suspected Lymphoma of the Spleen. Endoscopy 2006; 38(6): 617620.
  • 128
    Almasri N,Zaer F,Iturraspe J,Braylan R. Contribution of flow cytometry to the diagnosis of gastric lymphomas in endoscopic biopsy specimens. Mod Pathol 1997; 10: 650656.
  • 129
    Wu HSM,Millenson MM,Nicolaou N,Van Deerlin VM,Addya K,Lessin S,al Saleem T. Contribution of flow cytometry in the diagnosis of cutaneous lymphoid lesions. J Invest Dermatol 2003; 121: 15221530.
  • 130
    Zaer F,Braylan R,Zander D,Iturraspe J,Almasri N. Multiparametric flow cytometry in the diagnosis and characterization of low-grade pulmonary mucosa-associated lymphoid tissue lymphomas. Mod Pathol 1998; 11: 525532.
  • 131
    Fromm J,Kussick S,Wood B. Identification and purification of classical Hodgkin cells from lymph nodes by flow cytometry and flow cytometric cell sorting. Amer J Clin Pathol 2006; 126: 764780.
  • 132
    Duggan PR,Easton D,Luider J,Auer IA. Bone marrow staging of patients with non-Hodgkin lymphoma by flow cytometry: correlation with morphology. Cancer 2000; 88(4): 894899.
  • 133
    Hanson CA,Kurtin PJ,Katzmann JA,Hoyer JD,Li CY,Hodnefield JM,Meyers CH,Habermann TM,Witzig TE. Immunophenotypic analysis of peripheral blood and bone marrow in the staging of B-cell malignant lymphoma. Blood 1999; 94(11): 38893896.
  • 134
    van der Velden V,Hoogeveen P,Pieters R,van Dongen J. Impact of two independent bone marrow samples on minimal residual disease monitoring in childhood acute lymphoblastic leukaemia. Br J Haematol 2006; 133: 382388.
  • 135
    Ginaldi L,De Martinis M,Matutes E,Farahat N,Morilla R,Dyer M,Catovsky D. Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H. Leuk Res 1998; 22(2): 185191.
  • 136
    Perz J,Topaly J,Fruehauf S,Hensel M,Ho A. Level of CD 20-expression and efficacy of rituximab treatment in patients with resistant or relapsing B-cell prolymphocytic leukemia and B-cell chronic lymphocytic leukemia. Leuk Lymphoma 2002; 43(1): 149151.
  • 137
    Baer M. Detection of minimal residual disease in acute myeloid leukemia. Curr Oncol Rep 2002; 4(5): 398402.
  • 138
    Bjorklund E,Mazur J,Soderhall S,Porwit-MacDonald A. Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia. Leukemia 2003; 17(1): 138148.
  • 139
    Brinkman K,van Dongen JJ. Induction of clinical remission in T-large granular lymphocyte leukemia with cyclosporin A, monitored by use of immunophenotyping with Vbeta antibodies. Leukemia 1998; 12(2): 150154.
  • 140
    Campana D. Minimal residual disease studies in acute leukemia. Am J Clin Pathol 2004; 122( Suppl): S4757.
  • 141
    Coustan-Smith E,Ribeiro R,Rubnitz J,Razzouk B,Pui C,Pounds S,Andreansky M,Behm F,Raimondi S,Shurtleff S, and others. Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia. Br J Haematol 2003; 123(2): 243252.
  • 142
    Coustan-Smith E,Sancho J,Hancock M,Boyett J,Behm F,Raimondi S,Sandlund J,Rivera G,Rubnitz J,Ribeiro R, and others. Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood 2000; 96(8): 26912696.
  • 143
    Dworzak M,Froschl G,Printz D,Mann G,Potschger U,Muhlegger N,Fritsch G,Gadner H, Austrian Berlin-Frankfurt-Munster Study Group. Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood 2002; 99(6): 19521958.
  • 144
    Dworzak M,Panzer-Grumayer E. Flow cytometric detection of minimal residual disease in acute lymphoblastic leukemia. Leuk Lymphoma 2003; 44(9): 14451455.
  • 145
    Feller N,van der Pol M,van Stijn A,Weijers G,Westra A,Evertse B,Ossenkoppele G,Schuurhuis G. Minimal residual disease parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia. Leukemia 2004; 18(8): 13801390.
  • 146
    Griesinger F,Piro-Noack M,Kaib N,Falk M,Renziehausen A,Troff C,Grove D,Schnittger S,Buchner T,Ritter J, and others. Leukaemia-associated immunophenotypes (LAIP) are observed in 90% of adult and childhood acute lymphoblastic leukaemia: detection in remission marrow predicts outcome. Br J Haematol 1999; 105(1): 241255.
  • 147
    Kern W,Schoch C,Haferlach T,Schnittger S. Monitoring of minimal residual disease in acute myeloid leukemia. Crit Rev Oncol Hematol 2005; 56(2): 283309.
  • 148
    Kern W,Voskova D,Schoch C,Hiddemann W,Schnittger S,Haferlach T. Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia. Blood 2004; 104(10): 30783085.
  • 149
    Krampera M,Vitale A,Vincenzi C,Perbellini O,Guarini A,Annino L,Todeschini G,Camera A,Fabbiano F,Fioritoni G, and others. Outcome prediction by immunophenotypic minimal residual disease detection in adult T-cell acute lymphoblastic leukaemia. Br J Haematol 2003; 120(1): 7479.
  • 150
    Moreno C,Villamor N,Colomer D,Esteve J,Gine E,Muntanola A,Campo E,Bosch F,Montserrat E. Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia. Blood 2006; 107: 45634569.
  • 151
    Moreton P,Kennedy B,Lucas G,Leach M,Rassam S,Haynes A,Tighe J,Oscier D,Fegan C,Rawstron A, and others. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol 2005; 23(13): 29712979.
  • 152
    Raanani P,Ben-Bassat I. Detection of minimal residual disease in acute myelogenous leukemia. Acta Haematol 2004; 112(1–2): 4054.
  • 153
    Rawstron A,Kennedy B,Evans P,Davies F,Richards S,Haynes A,Russell N,Hale G,Morgan G,Jack A, and others. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood 2001; 98(1): 2935.
  • 154
    San Miguel J,Martinez A,Macedo A,Vidriales M,Lopez-Berges C,Gonzalez M,Caballero D,Garcia-Marcos M,Ramos F,Fernandez-Calvo J, and others. Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood 1997; 90(6): 24652470.
  • 155
    Sanchez J,Serrano J,Gomez P,Martinez F,Martin C,Madero L,Herrera C,Garcia J,Casano J,Torres A. Clinical value of immunological monitoring of minimal residual disease in acute lymphoblastic leukaemia after allogeneic transplantation. Br J Haematol 2002; 116(3): 686694.
  • 156
    Shulman H,Wells D,Gooley T,Myerson D,Bryant E,Loken M. The biologic significance of rare peripheral blasts after hematopoietic cell transplantation is predicted by multidimensional flow cytometry. Am J Clin Pathol 1999; 112(4): 513523.
  • 157
    Sievers E,Lange B,Alonzo T,Gerbing R,Bernstein I,Smith F,Arceci R,Woods W,Loken M. Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children's Cancer Group study of 252 patients with acute myeloid leukemia. Blood 2003; 101(9): 33983406.
  • 158
    Venditti A,Buccisano F,Del Poeta G,Maurillo L,Tamburini A,Cox C,Battaglia A,Catalano G,Del Moro B,Cudillo L, and others. Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood 2000; 96(12): 39483952.
  • 159
    Venditti A,Maurillo L,Buccisano F,Tamburini A,Del Poeta G,Del Principe M,Panetta P,Consalvo M,Mazzone C,Tendas A, and others. Multidimensional flow cytometry for detection of minimal residual disease in acute myeloid leukemia. Leuk Lymphoma 2003; 44(3): 445450.
  • 160
    Venditti A,Maurillo L,Buccisano F,Del Poeta G,Mazzone C,Tamburini A,Del Principe M,Consalvo M,De Fabritiis P,Cudillo L, and others. Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation. Leukemia 2003; 17(11): 21782182.
  • 161
    Vidriales M,Orfao A,San-Miguel J. Immunologic monitoring in adults with acute lymphoblastic leukemia. Curr Oncol Rep 2003; 5(5): 413418.
  • 162
    Vidriales M,Perez J,Lopez-Berges M,Gutierrez N,Ciudad J,Lucio P,Vazquez L,Garcia-Sanz R,del Canizo M,Fernandez-Calvo J, and others. Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value. Blood 2003; 101(12): 46954700.
  • 163
    Yin J,Grimwade D. Minimal residual disease evaluation in acute myeloid leukaemia. Lancet 2002; 360(9327): 160162.
  • 164
    Lai R,Arber D. Untreated chronic lymphocytic leukemia concurrent with or followed by acute myelogenous leukemia or myelodysplastic syndrome. A report of five cases and review of the literature. Am J Clin Pathol 1999; 111(3): 373378.
  • 165
    Martinez A,Pittaluga S,Villamor N,Colomer D,Rozman M,Raffeld M,Montserrat E,Campo E,Jaffe E. Clonal T-cell populations and increased risk for cytotoxic T-cell lymphomas in B-CLL patients: clinicopathologic observations and molecular analysis. Am J Surg Pathol 2004; 28(7): 849858.
  • 166
    Mitterbauer G,Schwarzmeier J,Mitterbauer M,Jaeger U,Fritsch G,Schwarzinger I. Myelodysplastic syndrome/acute myeloid leukemia supervening previously untreated chronic B-lymphocytic leukemia: demonstration of the concomitant presence of two different malignant clones by immunologic and molecular analysis. Ann Hematol 1997; 74: 193197.
  • 167
    Molica S. Second neoplasms in chronic lymphocytic leukemia: incidence and pathogenesis with emphasis on the role of different therapies. Leuk Lymphoma 2005; 46: 4954.
  • 168
    Muta T,Okamura T,Niho Y. Acute myelogenous leukemia concurrent with untreated chronic lymphocytic leukemia. Int J Hematol 2002; 75(2): 187190.
  • 169
    Saunthararajah Y,Molldrem JL. Coincident myelodysplastic syndrome and T-cell large granular lymphocytic disease: clinical and pathophysiological features. Br J Haematol 2001; 112(1): 195200.
  • 170
    Sokol L,Agosti S. Simultaneous manifestation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Am J Hematol 2004; 75(2): 107109.
  • 171
    Perez-Persona E,Vidriales B,Mmateo G,Mateos M,Garcia A,Galende J,Nuñez G,Alonso J,de las Heras N,Hernández J, and others. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 2007;doi:10.1182.
  • 172
    Alimena G,Breccia M,Latagliata R,Carmosino I,Russo E,Biondo F,Diverio D,Mancini M,Nanni M,Mandelli F. Sudden blast crisis in patients with Philadelphia chromosome-positive chronic myeloid leukemia who achieved complete cytogenetic remission after imatinib therapy. Cancer 2006; 107(5): 10081013.
  • 173
    Del Poeta G,Maurillo L,Venditti A,Buccisano F,Epiceno A,Capelli G,Tamburini A,Suppo G,Battaglia A,Del Principe M, and others. Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood 2001; 98(9): 26332639.
  • 174
    Birhiray R,Shaw G,Guldan S,Rudolf D,Delmastro D,Santabarbara P,Brettman L. Phenotypic transformation of CD52(pos) to CD52(neg) leukemic T cells as a mechanism for resistance to CAMPATH-1H. Leukemia 2002; 16(5): 861864.
  • 175
    Crespo M,Bosch F,Villamor N,Bellosillo B,Colomer D,Rozman M,Marce S,Lopez-Guillermo A,Campo E,Montserrat E. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003; 348(18): 17641775.
  • 176
    Durig J,Naschar M,Schmucker U,Renzing-Kohler K,Holter T,Huttmann A,Duhrsen U. CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia. Leukemia 2002; 16(1): 3035.
  • 177
    Schroers R,Griesinger F,Trumper L,Haase D,Kulle B,Klein-Hitpass L,Sellmann L,Duhrsen U,Durig J. Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia. Leukemia 2005; 19(5): 750758.
  • 178
    Rassenti LZ,Huynh L,Toy TL,Chen L,Keating MJ,Gribben JG,Neuberg DS,Flinn IW,Rai KR,Byrd JC, and others. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 2004; 351(9): 893901.
  • 179
    Richardson SJ,Matthews C,Catherwood MA,Alexander HD,Carey BS,Farrugia J,Gardiner A,Mould S,Oscier D,Copplestone JA, and others. ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL). Blood 2006; 107(9): 35843592.
  • 180
    Borowitz M,Shuster J,Carroll A,Nash M,Look A,Camitta B,Mahoney D,Lauer S,Pullen D. Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group Study. Blood 1997; 89(11): 39603966.
  • 181
    Donskoy E,Tausche F,Altman A,Quinn J,Goldschneider I. Association of immunophenotype with cerebrospinal fluid involvement in childhood B-lineage acute lymphoblastic leukemia. Am J Clin Pathol 1997; 107(5): 608616.
  • 182
    Solary E,Casasnovas R,Campos L,Bene M,Faure G,Maingon P,Falkenrodt A,Lenormand B,Genetet N. Surface markers in adult acute myeloblastic leukemia: correlation of CD19+, CD34+ and CD14+/DR--phenotypes with shorter survival. Groupe d'Etude Immunologique des Leucemies (GEIL). Leukemia 1992; 6(5): 393399.
  • 183
    Daniels J,Davis B,Houde-McGrail L,Byrd J. Clonal selection of CD56+ t(8;21) AML blasts: further suggestion of the adverse clinical significance of this biological marker? Br J Haematol 1999; 107(2): 381383.
  • 184
    Schabath R,Ratei R,Ludwig W. The prognostic significance of antigen expression in leukaemia. Best Pract Res Clin Haematol 2003; 16(4): 613628.
  • 185
    Junghanss C,Waak M,Knopp A,Kleine H,Kundt G,Leithauser M,Hilgendorf I,Wolff D,Casper J,Freund M. Multivariate analyses of prognostic factors in acute myeloid leukemia: relevance of cytogenetic abnormalities and CD34 expression. Neoplasma 2005; 52(5): 402410.
  • 186
    Ito S,Ishida Y,Oyake T,Satoh M,Aoki Y,Kowata S,Uchiyama T,Enomoto S,Sugawara T,Numaoka H, and others. Clinical and biological significance of CD56 antigen expression in acute promyelocytic leukemia. Leuk Lymphoma 2004; 45(9): 17831789.
  • 187
    Pope B,Brown R,Gibson J,Joshua D. The bone marrow plasma cell labeling index by flow cytometry. Cytometry 1999; 38: 286292.
  • 188
    Trendle M,Leong T,Kyle R,Katzmann J,Oken M,Kay N,Van Ness B,Greipp P. Prognostic significance of the S-phase fraction of light-chain-restricted cytoplasmic immunoglobulin (cIg) positive plasma cells in patients with newly diagnosed multiple myeloma enrolled on Eastern Cooperative Oncology Group treatment trial E9486. Am J Hematol 1999; 61: 232237.