https://orcid.org/0000-0002-3432-0489
Key Points
The use of melphalan-based conditioning regimen was associated with a significantly reduced risk of relapse.
A model combining pre-HCT blast percent, ICC criteria, and melphalan stratifies patients into low-, intermediate-, and high-risk categories.
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.
