Factors associated with survival after allogeneic transplantation for myeloid neoplasms harboring <i>TP53</i> mutations

Allogeneic hematopoietic stem cell transplant (alloHCT) is considered for all patients with myeloid neoplasms (MNs) harboring TP53 mutations (TP53mut). The aim of this international study across 7 transplant centers in the United States and Australia was to identify factors associated with improved post-alloHCT survival. Of 134 TP53mut MN cases who underwent alloHCT, 80% harbored complex karyotype; 94% of TP53 variants were localized to the DNA-binding domain (DBD). Most common comutations were ASXL1 (7%), TET2 (7%), and DNMT3A (6%). Median post-HCT survival was 1.03 years, and overall survival (OS) at 1 year, 2 years, and 3 years was 51.4%, 35.1%, and 25.1%, respectively. A total of 103 cases (76.9%) met the International Consensus Classification (ICC) criteria for MN with mutated TP53 (referred to as ICC-defined TP53mut MN hereafter). The 3-year OS of ICC-defined TP53mut was significantly shorter compared with that of other TP53mut MNs (3-year OS, 16.9% vs 54.9%; P = .002). ICC-defined TP53mut MNs was independently associated with inferior OS (hazard ratio [HR], 2.62; P = .019). The presence of non-DBD TP53mut only (HR, 3.40; P = .005), DNMT3A comutation (HR, 2.64; P = .016), and pre-alloHCT bone marrow blasts ≥5% (HR, 2.76; P = .006) was independently associated with inferior relapse-free survival (RFS), whereas melphalan-based conditioning was associated with superior RFS (HR, 0.52; P = .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 < .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.

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Journal
Blood Advances
Published
2025-03-14
DOI
https://doi.org/10.1182/bloodadvances.2024015335
Citations
11
Primary Topic
Acute Myeloid Leukemia Research
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article
Field-Weighted Citation Impact
19.47
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article

Factors associated with survival after allogeneic transplantation for myeloid neoplasms harboring TP53 mutations

Guru Subramanian Guru Murthy, Caner Saygin, Ernesto Ayala, Alia Cibich et al.
11 citations
Blood Advances
Acute Myeloid Leukemia Research
19.47
article

Factors associated with survival after allogeneic transplantation for myeloid neoplasms harboring TP53 mutations

Guru Subramanian Guru Murthy, Caner Saygin, Ernesto Ayala, Alia Cibich, Abhishek Avinash Mangaonkar, Ayalew Tefferi, Mohamed A. Kharfan‐Dabaja, Ashish Bajel, Mithun Vinod Shah, Mariam T. Nawas, Hemant S. Murthy, Saurabh Chhabra, James M. Foran, Anand Patel, Anmol Baranwal, Vedavyas Gannamani, Jeanne Palmer, Devendra Hiwase, Nandita Khera, Lisa Sproat, Chung Hoow Kok, Madiha Iqbal, Hassan B. Alkhateeb, Mehrdad Hefazi, Talha Badar, William J. Hogan, Mark Robert Litzow, Vivek Roy, Kimberly J. Langer, Danielle Rud
article en
11 citations

Abstract

Allogeneic hematopoietic stem cell transplant (alloHCT) is considered for all patients with myeloid neoplasms (MNs) harboring TP53 mutations (TP53mut). The aim of this international study across 7 transplant centers in the United States and Australia was to identify factors associated with improved post-alloHCT survival. Of 134 TP53mut MN cases who underwent alloHCT, 80% harbored complex karyotype; 94% of TP53 variants were localized to the DNA-binding domain (DBD). Most common comutations were ASXL1 (7%), TET2 (7%), and DNMT3A (6%). Median post-HCT survival was 1.03 years, and overall survival (OS) at 1 year, 2 years, and 3 years was 51.4%, 35.1%, and 25.1%, respectively. A total of 103 cases (76.9%) met the International Consensus Classification (ICC) criteria for MN with mutated TP53 (referred to as ICC-defined TP53mut MN hereafter). The 3-year OS of ICC-defined TP53mut was significantly shorter compared with that of other TP53mut MNs (3-year OS, 16.9% vs 54.9%; P = .002). ICC-defined TP53mut MNs was independently associated with inferior OS (hazard ratio [HR], 2.62; P = .019). The presence of non-DBD TP53mut only (HR, 3.40; P = .005), DNMT3A comutation (HR, 2.64; P = .016), and pre-alloHCT bone marrow blasts ≥5% (HR, 2.76; P = .006) was independently associated with inferior relapse-free survival (RFS), whereas melphalan-based conditioning was associated with superior RFS (HR, 0.52; P = .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 < .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.

Blood AdvancesVol. 9(14)
South Australia Pathology (AU), Royal Adelaide Hospital (AU), The Royal Melbourne Hospital (AU), Mayo Clinic (US), Medical College of Wisconsin (US), Peter MacCallum Cancer Centre (AU), Jacksonville College (US), WinnMed (US), University of Chicago (US), Cancer Centers of Southwest Oklahoma (US), Mayo Clinic in Arizona (US), Mayo Clinic Hospital (US), South Australian Health and Medical Research Institute (AU), Mayo Clinic in Florida (US), Central Adelaide Local Health Network
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Openalex Percentile: Top 1%
Acute Myeloid Leukemia Research
19.47
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