Comparison of Fludarabine and Total Body Irradiation (FluTBI) to Fludarabine without TBI (Flu) Based Nonmyeloabltive Conditioning (NMA) Prior to Hematopoietic Cell Transplantation (HCT) for Lymphoma

NMA doses of FluTBI result in successful donor chimerism and have the objective of controlling disease through a graft-versus-tumor effect. Other regimens without irradiation were developed, mainly for treatment of lymphoma, yet comparisons of HCT outcomes remain scant. We compared 382 FluTBI recipients to 515 Flu recipients prior to HCT from 2001 to 2011 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients were 40 years or older with lymphoma and received matched sibling, HLA matched at 8/8 or 7/8 unrelated donor (URD) bone marrow (BM) or peripheral blood (PBSC) grafts. FluTBI cohort had a higher number of patients with Karnofsky performance score (KPS) <90% (32% vs. 22%), more chronic lymphocytic leukemia (41% vs. 33%), more URD (68% vs. 51%), more PBSC (94% vs. 85%), less anti-thymocyte globulin use (11% vs. 15%), less rituximab in the conditioning (7% vs. 40%), and more mycophenolate mofetil-based graft vs. host disease prophylaxis (GVHD, 87% vs. 15%) compared to Flu. Impact on hematopoiesis differed according to the regimen with 24% and 43% of patients never dropping the absolute neutrophil count <500/µL and platelets <50,000/μL, respectively, with FluTBI comparing to 2% and 24% with Flu. Cumulative incidences at 100 days of grades II-IV and III-IV acute GVHD were 22% and 15% with FluTBI; and 17% (p=0.04) and 10% (p=0.02) for Flu, respectively. Corresponding rates of chronic GVHD at 1 year were 54% and 44% (p=0.004). Cumulative incidences at 3 years of transplant related mortality were 28% and 23% (p=0.13), and of progression were 36% and 34% (p=0.63) for FluTBI and Flu respectively. Multivariate analysis of TRM, progression, treatment failure and mortality showed no difference in outcomes according to the conditioning regimen. Variables associated with higher mortality were age 50-59y (Hazard Ratio [HR] 1.31, p=0.03) and ≥60y (HR 1.66, p<0.001) compared to 40-49y; KPS <90% (HR 1.49, p<0.001); and recipients of 8/8 matched URD (HR 1.28, p=0.02) and 7/8 matched URD (HR 1.94, p<0.001) compared to sibling donor HCT. The three-year probabilities of progression free survival were 40% and 41% (p=0.81), and overall survival were 50% and 55% (p=0.14) after adjusting for factors from the multivariate analysis. TBI regimens have less impact on blood counts immediate post-transplant period. Despite higher rates in acute and chronic GVHD with FluTBI, overall outcomes after HCT are comparable to non-TBI containing NMA regimens for lymphoma.