Second malignancies Secondary myelodysplastic syndrome and acute myelogenous leukemia are significant complications following autologous stem cell transplantation for lymphoma R Howe 1 , INM Micallef 2 , DJ Inwards 2 , SM Ansell 2 , GW Dewald 3 , A Dispenzieri 2 , DA Gastineau 2 , MA Gertz 2 , SM Geyer 4 , CA Hanson 3 , MQ Lacy 2 , A Tefferi 2 and MR Litzow 2 1 Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester MN 55905, USA; 2 Division of Hematology, Blood and Marrow Transplantation, Mayo Clinic, 200 First Street SW, Rochester MN 55905, USA; 3 Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester MN 55905, USA; and 4 Department of Biostatistics, Mayo Clinic, 200 First Street SW, Rochester MN 55905, USA Summary: Secondary myelodysplastic syndrome (sMDS) and acute myelogenous leukemia (AML) have been recognized with increasing frequency following autologous stem cell transplantation (ASCT). A retrospective analysis of 230 consecutive patients with Hodgkin’s lymphoma (HL, 64) and non-Hodgkin’s lymphoma (NHL, 166) who under- went ASCT was conducted to assess the incidence and risk factors for the development of sMDS/AML. At a median follow up of 41 months (range 0.1–177 months), 10 of 230 patients (4.3%) developed sMDS/AML. The 5-year- actuarial incidence of sMDS/AML was 13.1% and 5- year cumulative incidence by competing risk analysis was 4.2%. The median time to development of sMDS/AML was 39.9 months from the time of ASCT (range 12.1–62.0 months). Complex karyotypes at diagnosis of sMDS/ AML included structural anomalies and/or loss of chromosome 5 (eight patients), 7 (five patients), 17 (two patients) and 20 (two patients). All patients subsequently died, at a median of 6.8 months (range 0–39.9) from diagnosis of sMDS/AML. Fluorescent in situ hybridiza- tion (FISH) analysis for 5/5q- and 7/7q- were normal in all six patients whose pre-ASCT bone marrow was available for testing. Five of the six had samples available for testing at diagnosis of sMDS/AML and all had abnormal FISH results. By univariate statistical analysis, male gender (P ¼ 0.01), prior alkylating agents (mechlor- ethamine for HL, P ¼ 0.001 and cyclophosphamide for NHL, P ¼ 0.05) and the number of prior treatment regimens (P ¼ 0.04) were significantly associated with the development of sMDS/AML. Given the relatively low incidence rate of sMDS/AML, these analyses are primarily exploratory in nature but provide some insight into relevant risk factors and illustrate the risk of developing sMDS/AML after myeloablative conditioning and ASCT for lymphoma. Bone Marrow Transplantation (2003) 32, 317–324. doi:10.1038/sj.bmt.1704124 Keywords: secondary MDS; autologous stem cell trans- plantation; lymphoma Autologous stem cell transplantation (ASCT) is an increasingly important therapy for patients with Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Long-term disease-free survival rates post ASCT now approach 50% or more in some settings, and these patients may be cured of their lymphoma. 1–3 Although recurrence of disease remains the major cause of failure following ASCT with relapse rates approaching 40%, secondary myelodys- plastic syndrome (sMDS) and acute myelogenous leukemia (AML) have been recognized with increasing frequency post ASCT and are usually fatal. 4–8 The 5-year actuarial incidence rates of approximately 3–18% have been previously reported. 6,9–15 Factors shown to be associated with the development of sMDS and AML include older age, 9,13,14,16 amount and type of chemotherapy received prior to transplantation, 9,11,12,15,17–20 length of time between diagnosis of lymphoma and transplantation, 11 prior radia- tion therapy, 11,15 chemotherapy utilized for peripheral blood stem cell mobilization, 20 number, 21 and source 5,10,22,23 of stem cells reinfused and the use of total body irradiation as part of the conditioning regi- men. 7,14,16,24 The primary goals of this study were to assess the frequency of sMDS/AML post ASCT in patients with HL and NHL at Mayo Clinic Rochester, to further define possible risk factors for sMDS/AML that may predispose patients to developing this complication, and to describe the cytogenetic and FISH results on the bone marrow (BM) samples pre-ASCT and post-ASCT at diagnosis of sMDS/ AML. Received 18 September 2002; accepted 29 January 2003 Correspondence: Dr INM Micallef, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester MN 55905, USA Bone Marrow Transplantation (2003) 32, 317–324 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt