Factors associated with survival following allogeneic transplantation for myeloid neoplasms harboring TP53 mutations
- Author(s)
- Baranwal, A; Langer, K; Gannamani, V; Rud, D; Cibich, A; Saygin, C; Nawas, MT; Badar, T; Kharfan-Dabaja, MA; Ayala, E; Roy, V; Foran, JM; Murthy, HS; Iqbal, M; Palmer, JM; Sproat, L; Chhabra, S; Khera, N; Hefazi, M; Mangaonkar, AA; Hogan, WJ; Litzow, MR; Alkhateeb, HB; Tefferi, A; Kok, CH; Guru Murthy, GS; Patel, AA; Bajel, A; Hiwase, DK; Shah, MV;
- Journal Title
- Blood Advances
- Publication Type
- Online publication before print
- Abstract
- Allogeneic stem cell transplant (alloHCT) is considered for all patients with myeloid neoplasms (MN) harboring TP53-mutations (TP53mut). The aim of this international study across 7 transplant centers in USA and Australia was to identify factors associated with improved post-alloHCT survival. Of 134 TP53mut MN cases who underwent alloHCT, 80% harbored complex karyotype (CK); 94% of TP53 variants were localized to the DNA-binding domain (DBD). Most common co-mutations were ASXL1 (7%), TET2 (7%), and DNMT3A (6%). Median post-HCT survival was 1.03 years and OS at 1-, 2-, and 3-years was 51.4%, 35.1%, and 25.1%, respectively. One-hundred three (76.9%) cases met the International Consensus Classification (ICC) criteria for myeloid neoplasms with mutated TP53 (referred to as ICC-defined TP53mut MN hereafter). 3-year OS of ICC-defined TP53mut was significantly shorter compared to other TP53mut MN (3-year OS 16.9 vs. 54.9%, P=0.002). ICC-defined TP53mut MN was independently associated with inferior OS (HR 2.62, P=0.019). The presence of non-DBD TP53mut only (HR 3.40, P=0.005), DNMT3A co-mutation (HR 2.64, P=0.016), and pre-alloHCT bone marrow blasts ≥5% (HR 2.76, P=0.006) were independently associated with inferior RFS, while melphalan-based conditioning was associated with superior RFS (HR 0.52, P=0.005). Combining these variables, we constructed a hierarchical model that stratified patients into low-, intermediate, and high-risk categories with 1-year RFS of 81.3%, 31.3% and 6.7%, respectively (P<0.001). In conclusion, a subset of MN harboring TP53mut who have low blasts pre-alloHCT and received melphalan-based conditioning derived long-term benefit from alloHCT.
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2024015335
- Open Access at Publisher's Site
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Creation Date: 2025-03-27 06:21:33
Last Modified: 2025-03-27 06:22:10