Low rate of nonrelapse mortality in under 4-year-olds with ALL given chemo-conditioning for HSCT: Phase III FORUM study
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). In young children, total body irradiation (TBI) is associated with severe late sequelae.
In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of two TBI-free conditioning regimens in children with ALL =6 months (median follow-up: 3 years). 3-year OS was 0.63 (95% confidence interval [95% CI]: 0.52-0.72) and 0.76 (95% CI: 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (p = 0.075), respectively. 3-year EFS was 0.52 (95% CI: 0.41-0.61) and 0.51 (95% CI: 0.39-0.62), respectively (p = 0.794). Cumulative incidence of non-relapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI: 0.02-0.12) versus 0.03 (95% CI: 1 acute graft-versus-host disease (GvHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% receiving Flu/Thio/Treo (p = 0.049), while grade 3-4 occurred in 10% and 9% (p = 0.813). 3-year incidence of chronic GvHD was 0.07 (95% CI: 0.03-0.13) versus 0.05 (95% CI: 0.02-0.11), respectively (p = 0.518).
In conclusion, both chemo-conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure.