Increased non-relapse mortality in older people with allogeneic hematopoietic stem cell transplantation using fludarabine and myeloablative dose of busulfan-based regimen

Abstract Fludarabine and myeloablative doses of busulfan-based regimens (FluBu4) are used in a wide age range as a reduced toxicity conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT). However, their tolerability in older people has not been adequately examined. This retrospective study analyzed data from Transplant Registry Unified Management Program in Japan. Patients who were >15 years old (y/o), had hematological malignancies, and received their first HSCT using FluBu4 between 2006 and 2017 were included. They were categorized into the younger group (<60 y/o, N = 1295) and the older group (≥60 y/o, N = 993). The 3-year overall survival (OS) rate after HSCT was significantly worse in the older group than in the younger group (P < 0.01, 39.9% versus 48.5%). The 3-year non-relapse mortality (NRM) was significantly higher in the older group than in the younger group (P < 0.01, 30.9% versus 23.0%), and the 3-year cumulative incidence of relapse was comparable between the groups. According to the multivariate analysis, age ≥ 60 years was significantly associated with poor OS (P < 0.01) and high NRM (P < 0.01). In subgroup analysis of the older group, the use of additional chemotherapeutic drugs to FluBu4 was significantly associated with poor OS (P = 0.01) and high NRM (P < 0.01). Total body irradiation was significantly associated with high NRM (P < 0.01) and 1-year incidence of sinusoidal obstruction syndrome (P < 0.01) but not with OS. Thus, FluBu4 should be used with caution in older people.