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Sequential Regimen of Chemotherapy, Reduced-Intensity Conditioning for Allogeneic Stem-Cell Transplantation, and Prophylactic Donor Lymphocyte Transfusion in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

From the José Carreras Unit for Hematopoietic Stem Cell Transplantation, Department of Medicine III, Ludwig-Maximilians-University Hospital, Munich; and the Stem Cell Transplantation Unit, Deutsche Klinik für Diagnostik, Wiesbaden, Germany

Address reprint requests to Christoph Schmid, MD, José Carreras Unit for Hematopoietic Stem Cell Transplantation, Department of Medicine III, Ludwig-Maximilians-University Hospital, Marchioninistr 15, 81379 Munich, Germany; e-mail: Christoph.Schmid{at}med.uni-muenchen.de

PURPOSE: To improve the effect of allogeneic stem-cell transplantation by sequential use of intensive chemotherapy, reduced-intensity conditioning (RIC), and prophylactic donor lymphocyte transfusions (pDLTs) in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

PATIENTS AND METHODS: In a prospective study of 75 consecutive patients (median age, 52.3 years), high risk was defined by progressive or refractory disease (n = 59), second remission after early relapse (n = 8), or first remission with poor prognosis based on cytogenetics or delayed response to induction therapy (n = 8). Unfavorable karyotypes were found in 49% of informative patients, and 68 patients had medical contraindications against standard conditioning. Fludarabine (30 mg/m²), cytarabine (2 g/m²), and amsacrine (100 mg/m²) for 4 days were used for cytoreduction. After 3 days of rest, RIC consisted of 4 Gy total-body irradiation, antithymocyte globulin, and 80 to 120 mg/kg cyclophosphamide. Thirty-one patients had an HLA-identical sibling donor; 44 patients had an unrelated and/or HLA-mismatched donor. pDLT was given from day +120 in patients who were not receiving immunosuppression and were free of graft-versus-host disease (GvHD).

RESULTS: Complete remission was induced in 66 patients (88%). With a median follow-up of 35.1 months (range, 13.6 to 47.6 months), 2-year overall and leukemia-free survival were 42% and 40%, respectively. Outcome of patients with refractory disease or with complex cytogenetic aberrations was identical to that of better prognostic subgroups. Survival was best in patients who received high CD34⁺ cell numbers, and in patients with limited GvHD.

CONCLUSION: Sequential use of intensive chemotherapy, RIC transplantation, and pDLT represents a promising approach to the treatment of high-risk AML and MDS, particularly in patients with most unfavorable prognoses.

Presented in part as a preliminary analysis at the Annual Meeting of the German Society of Hematology and Oncology, October 29, 2002, Munich, Germany, and the Annual Meeting of the European Group of Blood and Marrow Transplantation, July 22, 2003, Istanbul, Turkey.

C.S. and M.S. contributed equally to this work.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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