Fludarabine as a risk factor for poor stem cell harvest, treatment-related MDS and AML in follicular lymphoma patients after autologous hematopoietic cell transplantation

Abstract

Fludarabine is an effective treatment for follicular lymphoma (FL), but exposure to it negatively impacts stem cell mobilization and may increase the risk of subsequent myelodysplastic syndrome and acute myelogenous leukemia (t-MDS/AML). We hypothesized that the risk that fludarabine imparts to stem cell mobilization and t-MDS/AML would be affected by dose or timing. All patients with FL treated at Cleveland Clinic from 1991 to 2007 with autologous hematopoietic cell transplantation were evaluated. Recursive partitioning analysis was used to explore associations of fludarabine and mitoxantrone dose and timing with poor stem cell harvest and t-MDS/AML. We identified 171 patients, of whom 52 previously received fludarabine. Patients exposed to fludarabine prior to auto-HCT were more likely to require >5 days of leukapheresis (P<0.001) and second stem cell mobilization (P<0.001), especially at a cumulative dose >150 mg/m(2). Univariable risk factors for t-MDS/AML included the number of chemotherapy regimens before auto-HCT, the need for >5 days of leukapheresis to collect CD34+ cells and fludarabine exposure in a dose-dependent manner, particularly when >500 mg/m(2). A cumulative dose of fludarabine >150 mg/m(2) increases the risk for poor stem cell harvests and any exposure increases the risk of t-MDS/AML, with the greatest risk being at doses >500 mg/m(2).