Fludarabine 30 mg/m/day x 5 and melphalan 140 mg/m x 1 (Flu-Mel140) is a commonly used RIC regimen. We hypothesized that addition of 200cGy total body irradiation (TBI) to Flu-Mel140 may improve antitumor activity and transplant outcomes.
Primary objectives was overall survival (OS) at 3-year. Secondary objectives were to assess the cumulative incidences of acute and chronic GVHD, relapse-free survival (RFS), relapse rate, and non-relapse mortality (NRM).
We retrospectively evaluated outcomes of patients receiving Flu-Mel140-TBI followed by HLA-matched donor allogeneic hematopoietic stem cell transplantation (alloSCT) using peripheral blood stem cells.
Eighty-one patients (median age, 58 years) underwent alloSCT between January 2008 and December 2018. Thirty-one percent patients had prior transplant, 32% had high or very-high disease risk index, and the donor was unrelated in 70% of patients. Grade 3-4 regimen-related toxicities were mucositis (37%), cardiac toxicity (17%), and renal toxicity (10%). The cumulative incidence of grade III-IV acute GVHD at day +100 was 24.7% and chronic GVHD at 1-year was 51.3%. Median follow-up for survival was 6.1 years. At 3-year, overall survival (OS) was 39.81%, RFS was 31.47%, and relapse rate was 30.5%. One-year NRM was 29.9%. Patients undergoing first transplant experienced improved OS compared to second or beyond (63.08% vs 42.31%, p=0.02). After adjusting for disease subtypes, age (≤55 vs 55), comorbidity index (CI), number of transplant and GVHD prophylaxis, multivariable analysis did not demonstrate any survival difference among disease subtypes. High CI (≥3) was predictive of adverse OS and NRM, while older age (>55 years) was associated with high NRM.
Our study shows that Flu-Mel140-TBI seems feasible, and provides durable disease control. Addition of TBI did not appear to improve outcomes compared to previously published reports of Flu-Mel140. Considerable NRM could result from the inclusion of patients with older age and prior transplants.
Copyright © 2021. Published by Elsevier Inc.
Outcomes of Fludarabine, Melphalan and Total Body Irradiation as a Reduced Intensity Conditioning Regimen in Matched Donor Allogeneic Peripheral Blood Stem Cell Transplantation: Outcomes of Flu-Mel-TBI.
