Risk factors before autologous stem-cell transplantation for lymphoma predict for secondary myelodysplasia and acute myelogenous leukemia.

Abstract

The risk factors for treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (AML) after autologous stem-cell transplantation (ASCT) are similar to those that increase the risk of difficult stem-cell harvests. We reviewed our experience in 526 patients with lymphoma treated by ASCT to determine whether difficult stem-cell harvests predict for an increased risk of t-MDS/AML. Autologous peripheral stem cells were initially mobilized with granulocyte colony-stimulating factor (G-CSF; or granulocyte-macrophage colony-stimulating factor) alone (n = 334), etoposide and G-CSF (n = 166), or cyclophosphamide and G-CSF with or without etoposide (n = 26). Difficult harvests were those that required more than 5 days to collect enough stem cells and those that required additional attempts with etoposide and/or cyclophosphamide plus G-CSF (n = 52). All patients were then treated with high-dose chemotherapy alone and observed for outcome. With a median follow-up time for surviving patients of 69 months, 20 patients developed t-MDS/AML, for an actuarial incidence of 6.8% at 10 years. Pretransplantation characteristics, including age, diagnosis of non-Hodgkin's lymphoma or Hodgkin's disease, bone marrow involvement, prior radiation therapy, prior exposure to chemotherapy, lactate dehydrogenase at the time of ASCT, disease status, and method of stem-cell mobilization, were then analyzed with respect to the subsequent development of t-MDS/AML. By multivariable analysis, prior exposure to radiation therapy, four or more chemotherapy regimens, and more than 5 days of apheresis needed to harvest enough stem cells were identified as independent risk factors for t-MDS/AML. Bootstrap analysis confirmed these results. These results suggest that identifiable pretransplantation factors predict for t-MDS/AML after ASCT.