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Allogeneic blood stem cell transplantation after a reduced-intensity, preparative regimen
A pilot study in patients with refractory malignancies
Article first published online: 25 APR 2002
Copyright © 2002 American Cancer Society
Volume 94, Issue 9, pages 2409–2415, 1 May 2002
How to Cite
Pedrazzoli, P., Da Prada, G. A., Giorgiani, G., Schiavo, R., Zambelli, A., Giraldi, E., Landonio, G., Locatelli, F., Siena, S. and Cuna, G. R. D. (2002), Allogeneic blood stem cell transplantation after a reduced-intensity, preparative regimen. Cancer, 94: 2409–2415. doi: 10.1002/cncr.10491
- Issue published online: 25 APR 2002
- Article first published online: 25 APR 2002
- Manuscript Accepted: 18 NOV 2001
- Manuscript Revised: 8 NOV 2001
- Manuscript Received: 20 SEP 2001
- Associazione Italiana Ricerca sul Cancro
- Consiglio Nazionale delle Ricerche
- Ministero dell'Università e della Ricerca Scientifica
- Istituto di Ricovero e Cura a Carattere Scientifico
- Policlinico S. Matteo
- Associazione ONLUS Oncologia Ca' Granda, Milano
- allogeneic blood stem cell transplantation;
- graft-versus-tumor disease;
- performance status;
- refractory malignancies
The immune-mediated graft-versus-tumor (GVT) effect plays a therapeutic role in the treatment of patients with hematologic malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). More recently, it was reported that a GVT effect also occurred in patients who underwent transplantation for metastatic renal carcinoma. The authors carried out a pilot trial of allogeneic transplantation after a reduced-intensity, preparative regimen in patients with refractory malignancies, including solid tumors. The objectives of the current study were to evaluate the feasibility of this approach in terms of toxicity and engraftment and to document evidence of GVT effects.
Seventeen patients with Stage IV malignancies (7 patients with renal cell carcinoma, 3 patients with sarcoma, 2 patients with breast carcinoma, 2 patients with Hodgkin disease, 1 patient with ovarian carcinoma, 1 patient with melanoma, and 1 patient with both melanoma and renal cell carcinoma) that were not amenable to further conventional treatment were enrolled. The median patient age was 43 years (range, 10–60 years). The Eastern Cooperative Oncology Group performance status (PS) was 0–1 in 11 patients and 2–3 in 6 patients. Preparative treatment consisted of reduced-intensity chemotherapy with fludarabine (30 mg/m2 per day for 4 consecutive days) and cyclophosphamide (30 mg/Kg per day for 2 consecutive days) prior to allogeneic HSCT from a human leukocyte antigen-identical sibling. The median number of CD34+ cells infused was 6.06 × 106/kg (range, 1.5–14.0 × 106/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin-A and short-term methotrexate.
Patients who had a PS of 2–3 prior to undergoing HSCT experienced Grade 4 hematologic toxicities and Grade ≥ 3 organ toxicities and died of either treatment-related complications or disease progression within 100 days from transplantation. By contrast, 10 of 11 patients who had a PS of 0–1 prior to undergoing HSCT experienced only short-lasting, Grade ≤ 3 neutropenia and thrombocytopenia and no organ toxicity; 1 of 10 patients died of graft failure on Day +29 after undergoing HSCT. By Day +90, 100% donor chimerism was documented in all patients with a past history of heavy chemotherapy, whereas mixed donor chimerism was observed in the 4 patients with a past history of only 1 line of chemotherapy and/or immunotherapy prior to entering the HSCT program. Grade 2–3 acute GVHD occurred in 5 patients. Among patients with a follow-up > 100 days, 2 complete responses and 3 transitory partial responses were recorded.
With this conditioning regimen, full donor chimerism was achieved rapidly only in patients who had received previous intensive chemotherapy. In a proportion of patients with refractory malignancies, allogeneic transplantation resulted in tumor regression. This novel therapeutic strategy may provide little benefit in patients with poor PS and rapidly progressing disease. Cancer 2002;94:2409–15. © 2002 American Cancer Society.