Remission Status Prior to Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia/Myelodysplastic Syndrome Patients Harboring Single-Hit or Multi-Hit p53 Mutations Does Not Impact Outcome.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
Patients with TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent a heterogeneous group and have a poor prognosis even after allogeneic stem cell transplantation (allo-SCT). This study examined the post-transplantation outcomes of patients based on their pretransplantation TP53 mutational status to assess the impact of multi-hit and single-hit mutations. A retrospective analysis was conducted on 81 adult patients with MDS/AML (30 with single-hit mutations and 51 with multi-hit mutations) who underwent allo-SCT at the University Medical Center Hamburg between 2014 and 2024. The pretransplantation remission status was evaluated through cytomorphologic, next-generation sequencing (NGS), and cytogenetic methodologies. The study cohort comprised 42 male patients with a median age of 63 years (range, 18 to 78 years). Most patients had received reduced-intensity conditioning (62%), had received an allograft from an unrelated donor (75%), and were categorized as non-complete remission (CR) (60%). The 3-year overall survival (OS) and leukemia-free survival (LFS) rates were 25% and 23% for patients with AML and 43% and 30% for patients with MDS (P = .20 and .29, respectively). The 3-year OS (34% versus 28% versus 42%; P = .52) and LFS (32% versus 26% versus 26%, P = .69) rates were comparable among patients in CR, those in non-CR, and those untreated at allo-SCT, respectively. The 3-year OS rate for patients with a single-hit TP53 mutation was 35%, compared to 27% for patients with a multi-hit mutation (P = .15). The 3-year LFS rate for the single-hit cohort was 26%, compared to 18% for the multi-hit cohort (P = .047). Patients treated with fludarabine and treosulfan had the highest 3-year OS (58%) and LFS (46%) rates compared to patients treated with other regimens (P = .051 and .025, respectively). The cumulative incidence of relapse at 3 years was comparable between the multi-hit and single-hit cohorts (50% versus 56%; P = .70). The patients with multi-hit status experienced post-transplantation relapse earlier (median, 80 days [range, 8 to 1107 days] versus 128 days [range, 78 to 794 days]; P = .037). The cumulative incidence of nonrelapse mortality at 3 years was 16% in the single-hit cohort and 29% in the multi-hit cohort (P = .15). The majority of patients from the multi-hit cohort received more than 2 chemotherapy cycles before allo-SCT, compared to the single-hit cohort (P = .14). The multi-hit TP53 mutation was significantly associated with a reduced LFS rate in MDS/AML patients compared to those with a single-hit TP53 mutation. Patients with a single-hit or multi-hit TP53 may achieve a long-term survival rate of approximately 30% and should be considered candidates for transplantation, even in the absence of complete remission.