Nonmyeloablative allogeneic hematopoietic stem cell transplant for the treatment of patients with hematologic malignancies using busulfan, fludarabine, and total body irradiation conditioning is effective in an elderly and infirm population.

The BuFluTBI conditioning regimen was designed with the primary goal of reducing non-relapse mortality (NRM) while maximizing primary disease control in patients ineligible for myeloablative conditioning. Patients with hematologic malignancies for whom limited long-term survival was expected with standard therapy were administered an outpatient conditioning regimen of busulfan 3.2 mg/kg IV on day -5, fludarabine 30 mg/m(2) IV on days -4, -3, -2, and 200 cGy of total body irradiation (TBI) followed by stem cell infusion from related or unrelated donors. GVHD prophylaxis included cyclosporine and mycophenolate mofetil. 147 patients were enrolled from 2005-2011; 59% with myeloid disease and 41% with lymphoid disease. The median age was 64, and the median comorbidity index (HCT-CI) score was 3. Overall survival (OS), with 3.2 years median follow-up, was 60% at 1 year and 48% at 2 years, with projected OS 37% at 5 years. Relapse rates were 29% at 1 year and 33% at 2 years, with relapse mortality of 13% at 1 year, and 20% at 2 years. Nonrelapse mortality (NRM) at 1 year was 27% and 33% at 2 years. 54% of patients developed grade II-IV aGVHD and 67% of patients developed cGVHD within 2 years. On multivariate analysis, HCT-CI score 4 or greater, pre-transplant KPS less than 90, delayed platelet engraftment of more than 15 days, and grade II-IV aGVHD were found to be independent predictors of poor survival. There was no difference in OS or PFS between lymphoid and myeloid malignancies. BuFluTBI is an efficacious NMA regimen, active in both myeloid and lymphoid disease, and is ideally suited for use in patients age 65 and older or with an HCT-CI of 4 or greater.

Induction bortezomib in Al amyloidosis followed by high dose melphalan and autologous stem cell transplantation: a single institution retrospective study.

INTRODUCTION/BACKGROUND: High-dose melphalan (HDM) followed by autologous stem cell transplant (ASCT) for light chain amyloidosis (AL) was performed in 31 patients at Oregon Health and Science University between 2005 and 2012. Fifteen patients had cardiac involvement. PATIENTS AND METHODS: Patients received melphalan 200 mg/m(2) or dose-adjusted HDM (100-140 mg/m(2)) depending on high risk features. Thirteen patients proceeded directly to ASCT after diagnosis, 12 patients received a bortezomib-containing regimen, and 6 received a variety of other induction regimens. RESULTS: The day 100 treatment-related mortality was 9.6%. Overall hematologic (ORR) and organ response rates (OR) in the whole cohort after ASCT were 77% and 58%. ORR and OR in the bortezomib pretreated group were 92% and 75% vs. 69% and 54% in the group that received no pretreatment. The median time to maximum hematologic response after ASCT was reduced in the group that received bortezomib induction (3 vs. 14 months). Overall cardiac response rate was 60%; 100% in patients pretreated with bortezomib and 43% in those without induction treatment. With a median follow-up of 2.9 years, the 3-year progression-free and overall survival rates in the entire cohort were 66% and 73% and in those with cardiac involvement, 73% and 80%. CONCLUSION: We observed that bortezomib-based induction is well tolerated in patients with and without cardiac involvement and suggest that this approach be studied in prospective multi-institutional trials.