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

Abstract

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-α) 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-α. 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-α 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.