Clinical outcomes of <i>TP53</i> -mutated myeloid neoplasms after allogeneic hematopoietic cell transplantation: A Canadian multicenter propensity score–matched analysis.

Abstract

6553 Background: TP53 mutations define a biologically aggressive subset of myeloid malignancies with poor outcomes. We evaluated clinical, disease-related, and transplant-associated variables influencing post-allogeneic hematopoietic cell transplant (HCT) outcomes in this high-risk group. Methods: We conducted a retrospective multicenter study across 10 Canadian transplant centers, including 153 individuals with TP53 -mutated and 2,207 patients with TP53 wild-type acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) from the Cell Therapy and Transplant Canada (CTTC) registry. Propensity score matching was performed to account for baseline differences. The primary outcomes were relapse and overall survival (OS) after HCT. Results: Presence of TP53 mutation was associated with increased risk of relapse compared with TP53 wild-type (HR 2.21; 95% CI: 1.5–3.1; p&lt;0.01). Among TP53 -mutated patients (n=153), with a median follow-up of 35.8 months (Q1-Q3: 29-48), the 2-year cumulative incidence of relapse was 53.2% (95% CI: 44.4-61.2), and OS 40.1% (95% CI: 31.6-48.4). In multivariable analysis, multi-hit TP53 mutations (HR 2.17, 95% CI: 1.3-3.7; p&lt;0.01), and graft-vs-host disease (GVHD) prophylaxis regimens containing anti-thymocyte globulin (ATG) with (HR 3.53, 95% CI: 1.5-8.1; p&lt;0.01) or without (HR 2.59, 95% CI: 1.2-5.6; p=0.01) post-transplant cyclophosphamide were associated with higher relapse risk. Conditioning regimen intensity, and chronic GVHD, modelled as a time-dependent covariable, did not significantly impact relapse, while chronic GVHD was associated with improved OS (HR 0.46; 95% CI: 0.2-0.9, p=0.03). Conclusions: In patients with myeloid malignancies, TP53 mutations are associated with a high risk of relapse and poor survival after HCT, while chronic GVHD appears to be protective, underscoring the importance of careful selection of GVHD prophylaxis and the need for effective post-transplant strategies in this high-risk population. Multivariable analysis. Variable Hazard Ratio 95% CI p value Relapse TP53 mutation status Single hit Multi hit Ref2.17 Ref1.27-3.71 Ref0.005 Disease risk index Intermediate High/very high Ref1.53 Ref0.77-3.03 Ref0.220 GVHD prophylaxis CNI-MTX ATG-CNI-MTX ATG-PTCY-CNI PTCY-CNI-MMF Ref2.593.531.66 Ref1.21-5.561.52-8.170.58-4.74 Ref0.0140.0030.350 Chronic GVHD (time dependent) 1.25 0.63–2.45 0.526 Overall survival TP53 mutation status Single hit Multi hit Ref2.26 Ref1.30-3.90 Ref0.003 Disease risk index Intermediate High/very high Ref0.93 Ref0.49-1.77 Ref0.823 GVHD prophylaxis CNI-MTX ATG-CNI-MTX ATG-PTCY-CNI PTCY-CNI-MMF Ref2.181.621.04 Ref1.12-4.240.73-3.610.36-2.99 Ref0.0210.2360.949 Chronic GVHD (time dependent) 0.46 0.23-0.93 0.030