Transplant versus no transplant in myelodysplastic syndrome and acute myeloid leukemia with TP53 mutation; a referral center experience

Abstract A remarkably high rate of post‐transplant relapse in patients with TP53‐mutated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) calls to question the utility of allogeneic stem cell transplant (HSCT). We, therefore, performed a retrospective analysis to compare the outcomes between HSCT ( N = 38) versus non‐HSCT ( N = 45) approaches. Patients in the HSCT cohort were younger (median age 63 vs. 72) while patients in the non‐HSCT cohort more commonly had complex karyotype with chromosome 17 aberrancy and 5q deletion ( p < .01). A total of 69 TP53 variants including 64 pathogenic variants, and 5 variants of undetermined significance were detected. Nine patients (4 in HSCT and 5 in non‐HSCT) had multi‐hit TP53 variants. After induction: 57.9% versus 56.6% in the HSCT versus non‐HSCT cohort achieved morphologic complete remission. Median time to HSCT was 6 months and median follow‐up was 15.1 months for HSCT and 5.7 months for non‐HSCT. Median disease‐free survival (DFS) and overall survival (OS) were 11.7 and 15.9 months for HSCT, and 4.1 and 5.7 months for non‐HSCT cohorts, respectively. Non‐relapse mortality at 12 months was 22% versus 44% for HSCT versus non‐HSCT. In the HSCT cohort, the rate of grade II–IV acute and chronic graft‐versus‐host disease (GVHD) was 55% and 18%, respectively. None of the patients from the non‐HSCT cohort were alive while four patients from the HSCT cohort were alive, in remission, and without GVHD (GRFS) at the time of abstraction. Better treatment strategies for patients with TP53‐mutated MDS/AML remain an area of unmet clinical need.