Clinical Outcomes of TP53 Mutated Myelodysplastic Syndrome/Acute Myeloid Leukemia; A Single Center Experience

Introduction TP53 mutated MDS/AML has dismal outcomes. Despite allogeneic stem cell transplant (HSCT), the rate of relapse remains high. But as the only potential curative option, HSCT is still offered to select patients. Methods We conducted chart review of patients treated between 2012 to 2023. TP53 mutation was detected by NGS using Ion Torrent AmpliSeq technology targeting 30 AML-related genes and were categorized from COSMIC and ClinVar database. Karyotype determined from unstimulated marrow cells and our FISH probe analyzes 300 nuclei.High intensity induction (Hi) included high dose chemotherapy (7+3) with/without FLT3 inhibitor. Low intensity induction (Lo) included hypomethylating agent with/without venetoclax. Statistical Analysis Time was calculated from diagnosis to relapse for disease free survival (DFS) and death for overall survival (OS). Non-relapse mortality (NRM) was calculated from diagnosis to death where relapse was a competing event. Results We identified 83 patients (38 HSCT and 45 non-HSCT). Patients in the HSCT arm were younger (median age 63 vs 72 years old). Both cohorts had similar proportion of female patients (23.7% vs. 33.3%) and patients with more than 20% blasts by morphology at diagnosis (44.7% vs. 55.6%). Patients in the non-HSCT cohort more commonly had CK-17 and 5q deletion (5qdel) (p < 0.01) but both cohorts had similar rate of monosomy 7 (p = 0.15). Comparable proportion of patients received Lo but more patients in the HSCT cohort were induced with Hi (34.2% vs 15.6%, p < 0.01). More than half of the patients achieve morphologic complete remission (CR) at 57.9% vs 56.6% in the HSCT vs non-HSCT cohort, respectively, and most were measurable residual disease (MRD) positive (57.9% and 76.5%). No statistical difference in the rate of CR after Lo vs Hi (60.8% vs 47.1%, p=0.32). Median time to transplant was 6 months (mo).Median follow up was 15.1 mo. for HSCT and 5.7 mo. for non-HSCT. Median DFS and OS was 11.7 mo. and 15.9 mo. for HSCT, and 4.1 and 5.7 mo. for non-HSCT respectively. Non-relapse mortality (NRM) at 12 mo was 22% vs 44% for HSCT vs non-HSCT. In the HSCT cohort, 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 were alive while four patients from the HSCT were alive, in remission and without GVHD (GRFS) at the time of abstraction.Interestingly, two patients from HSCT relapsed after two years of CR. They both received reduced intensity match unrelated HSCT. One patient had TP53 R175H variant and the other E286G variant, both variants re-emerged at the time of relapse. Conclusion The clinical outcomes of TP53 mutated MDS/AML remains discouraging. Select patients may benefit from HSCT but a large proportion of patients still experience post-transplant relapse. Better treatment strategy is direly needed for this distinct patient population.