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Moderate Increase of Secondary Hematologic Malignancies After Myeloablative Radiochemotherapy and Autologous Stem-Cell Transplantation in Patients With Indolent Lymphoma: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group

From the Departments of Internal Medicine III and Medical Informatics, Biometrics and Epidemiology (IBE), Ludwig-Maximilians University, Munich, Germany

Address reprint requests to Georg Lenz, MD, University Hospital Grosshadern, Department of Internal Medicine III, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany; e-mail: georg.lenz{at}med3.med.uni-muenchen.de

PURPOSE: An increased risk of therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) after high-dose therapy and autologous stem-cell transplantation (ASCT) for malignant lymphoma has been described by several studies, reporting a highly variable incidence ranging from 1% to 12%. To assess this risk more precisely, the German Low Grade Lymphoma Study Group investigated the incidence of t-MDS/t-AML after ASCT on the basis of a randomized comparison of ASCT versus interferon alfa (IFN-) maintenance in indolent lymphoma.

PATIENTS AND METHODS: Between 1996 and 2002, 440 patients with indolent lymphoma were randomly assigned after a cyclophosphamide, doxorubicin, vincristine, and prednisone–like induction therapy regimen to myeloablative radiochemotherapy followed by ASCT or IFN-. The incidence of secondary hematologic malignancies was determined by standardized follow-up of all study patients. Bone marrow samples from patients with proven or suspected t-MDS/t-AML were centrally reviewed.

RESULTS: After a median follow-up of 44 months, 431 patients were assessable. Five of 195 patients developed a secondary hematologic malignancy after ASCT. Two of these patients developed a secondary AML. Accordingly, the estimated 5-year risk for secondary hematologic neoplasias after ASCT was 3.8%. In contrast, in the IFN- arm, the 5-year risk of hematologic neoplasias was 0.0% (P = .0248).

CONCLUSION: The data of this randomized trial demonstrate an increased risk of secondary hematologic malignancies after myeloablative radiochemotherapy and ASCT compared with conventional chemotherapy. However, as ASCT significantly improves progression-free survival, it is currently not evident to what extent the higher rate of t-MDS/t-AML will diminish the benefit of ASCT in indolent lymphoma.

Supported as part of the Competence Network Malignant Lymphoma (BMBF grant No. 01 GI 9994).

Presented in part at the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 6-9, 2003.

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

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