Myeloablative Intravenous Pharmacokinetically Targeted Busulfan Plus Fludarabine As Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With Non-Hodgkin Lymphoma

Traditional myeloablative conditioning regimens in allogeneic transplantation are associated with high nonrelapse mortality (NRM). We present the results of the use of intravenous busulfan and fludarabine (BuFlu) in 60 patients with non-Hodgkin lymphoma (NHL). Our data show that BuFlu offers an alternative option when myeloablation is deemed necessary. Background: Mortality associated with allogeneic hematopoietic cell transplantation (allo-HOT) has limited its broader application in patients with non-Hodgkin lymphoma (NHL). Pharmacokinetic treatment with targeted intravenous busulfan combined with fludarabine (BuFlu) was developed as a preparative regimen for acute leukemia and myelodysplasia. Data from this regimen in lymphoid malignancies are limited. Patients and Methods: We assessed outcomes in 60 consecutive patients with various subtypes of NHL and a median age of 54 years (range, 27-68 years) who received allo-HCT with targeted intravenous BuFlu between December 2004 and August 2010. The median number of previous therapies was 3 (range, 1-8) and median time from diagnosis to HOT was 32 months (range, 4.5-177.5 months). Results: At conditioning, 28 (47%) patients had a complete response (CR). Graft versus host disease (GVHD) prophylaxis consisted of tacrolimus plus methotrexate in 65% of cases. Donors were matched/related (n = 32 [53%]), matched/unrelated (n = 21 [35%]), or mismatched/unrelated (n = 7 [12%]). All patients underwent grafting. The cumulative incidence of grade II/IV acute GVHD was 74% (grade III/IV was 20%). The 2-year cumulative incidence of moderate to severe chronic GVHD was 62%. Nonrelapse mortality (NRM) at 100 days and 3 years was 10% and 25%, respectively. The cumulative incidence of relapse was 27%. Three-year progression-free and overall survival for all patients was 47.8% and 55%, respectively. Conclusion: Targeted intravenous BuFlu is a relatively well tolerated regimen and offers an alternative option when myeloablation is deemed necessary in patients with NHL.