Incidence of post transplant myelodysplasia/acute leukemia in non-Hodgkin's lymphoma patients compared with Hodgkin's disease patients undergoing autologous transplantation following cyclophosphamide, carmustine, and etoposide (CBV)

Secondary malignancies, particularly myelodysplasia (MDS), are serious events following high dose therapy with autologous stem cell support. We observed a higher frequency of secondary malignancies in patients with Hodgkin's disease (HD) than in patients with non-Hodgkin's lymphoma (NHL) undergoing high dose therapy with the same non-TBI conditioning regimen. Three hundred patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) were treated with cyclophosphamide. carmustine and etoposide and autologous stem cell support from 1986 through 1994. Median follow up of survivors is 3.9 years. Five-year survival is 51% for HD and 48% for NHL. Eleven patients developed second malignancies (9/150 treated for HD vs. 2/150 treated for NHL) a median of 2.4 years from transplantation and 5.2 years from initial diagnosis. Six patients had myelodysplasia or acute leukemia (MDS/AML) and 5 had lymphomas or solid tumors. Actuarial risk of MDS/AML at five years for patients transplanted for non-Hodgkin's lymphoma is 3% (95 % CI 0.6-9.6%). HD patients had significantly different pretreatment characteristics than patients with NHL. A Cox model showed that greater number of prior relapses and prior radiation therapy were significant risk factors for the development of MDS/AML. These data suggest that CBV is associated with a lower risk of secondary MDS/AML than TBI containing regimens and that much of the risk is associated with thtr pre-transplantation therapy. The use of autotransplantation early in the course of therapy for relapsed lymphoma might prevent some cases of MDS/AML.