Transplantation outcomes in patients with Down syndrome-associated acute lymphoblastic leukaemia: Implications for treatment intensity and the use of novel therapies.
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Down syndrome-associated acute lymphoblastic leukaemia (DS-ALL) is associated with inferior outcomes compared with non-DS-ALL; however, data on haematopoietic stem cell transplantation (HSCT) in DS-ALL remain limited. We analysed nationwide data of patients aged <30 years with B-cell precursor ALL who underwent first allogeneic HSCT between 2000 and 2022 in Japan. In total, 56 patients with DS-ALL and 3873 with non-DS-ALL were identified. The incidences of neutrophil engraftment, grade II-IV acute graft-versus-host disease and chronic graft-versus-host disease were comparable between groups. The 4-year event-free survival (EFS) was lower in DS-ALL than in non-DS-ALL (40.3% vs. 55.2%), but was similar when stratified by disease status at HSCT. The 4-year EFS rates in first and second complete remission (CR) were 62.7% and 48.2% in DS-ALL and 69.5% and 56.0% in non-DS-ALL respectively. Relapse, rather than non-relapse mortality (NRM), was the leading cause of treatment failure in DS-ALL. Among patients with DS-ALL undergoing HSCT in CR1/2, myeloablative conditioning (MAC) showed a trend towards superior EFS compared with reduced-intensity conditioning (RIC), which was associated with a higher incidence of NRM. Accordingly, patients in CR1/2 who are unable to tolerate MAC are considered good candidates for emerging novel therapies rather than RIC-HSCT.