TP53 mutation in allogeneic hematopoietic cell transplantation for de novo myelodysplastic syndrome

Abstract

We investigated the prognostic role of somatic mutations in allogeneic hematopoietic cell transplantation (HCT) for de novo myelodysplastic syndrome (MDS). We performed targeted deep sequencing analysis of 26 genes on bone marrow samples obtained within 6 weeks before HCT from 202 patients with de novo MDS. Overall, 76% of patients carried one or more somatic mutations, and TP53 mutation was present in 23 patients (11.4%). Overall survival (OS) at 5 years was 63.6%, cumulative incidence of relapse (CIR) was 18.6%, event-free survival (EFS) was 58.5%, and non-relapse mortality (NRM) was 22.9%. TP53 mutation was an independent risk factor for lower OS (41% vs. 67%; P = 0.001), higher CIR (49% vs. 15%; P = 0.001), and lower EFS (38% vs. 61%; P = 0.005), but not for NRM (13% vs. 24%). N-RAS mutation was an independent risk factor for higher CIR (HR, 5.91; P = 0.008). TP53 mutation did not have significant interactions with conditioning intensity or the occurrence of graft-versus-host disease with regard to post-transplant outcomes. In conclusion, TP53 mutation was significantly associated with poor outcomes after HCT for patients with de novo MDS, mainly due to a higher incidence of disease relapse.

Keywords: Allogeneic HCT; De novo MDS; Somatic mutation; Survival; TP53 mutation.