Faculty Collaboration Database

Allogeneic Hematopoietic Cell Transplantation Improves Outcome in Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis of the Blood and Marrow Transplant Clinical Trials Network 1102 Study. J Clin Oncol 2023 Oct 01;41(28):4497-4510

Date

08/23/2023

Pubmed ID

37607457

Pubmed Central ID

PMC10552956

DOI

10.1200/JCO.23.00866

Scopus ID

2-s2.0-85175320632 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor v no donor) study.

METHODS: We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with TP53 mutations were classified as TP53^multihit if two alleles were altered (via point mutation, deletion, or copy-neutral loss of heterozygosity).

RESULTS: The distribution of gene mutations was similar in the donor and no donor arms, with TP53 (28% v 29%; P = .89), ASXL1 (23% v 29%; P = .37), and SRSF2 (16% v 16%; P = .99) being most common. OS in patients with a TP53 mutation was worse compared with patients without TP53 mutation (21% ± 5% [SE] v 52% ± 4% at 3 years; P < .001). Among those with a TP53 mutation, OS was similar between TP53^single versus TP53^multihit (22% ± 8% v 20% ± 6% at 3 years; P = .31). Considering HCT as a time-dependent covariate, patients with a TP53 mutation who underwent HCT had improved OS compared with non-HCT treatment (OS at 3 years: 23% ± 7% v 11% ± 7%; P = .04), associated with a hazard ratio of 3.89; 95% CI, 1.87 to 8.12; P < .001 after adjustment for covariates. OS among patients with molecular IPSS (IPSS-M) very high risk without a TP53 mutation was significantly improved if they had a donor (68% ± 10% v 0% ± 12% at 3 years; P = .001).

CONCLUSION: HCT improved OS compared with non-HCT treatment in patients with TP53 mutations irrespective of TP53 allelic status. Patients with IPSS-M very high risk without a TP53 mutation had favorable outcomes when a donor was available.

Author List

Versluis J, Saber W, Tsai HK, Gibson CJ, Dillon LW, Mishra A, McGuirk J, Maziarz RT, Westervelt P, Hegde P, Mukherjee D, Martens MJ, Logan B, Horowitz M, Hourigan CS, Nakamura R, Cutler C, Lindsley RC, Blood and Marrow Transplant Clinical Trials Network

Authors

Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Michael Martens PhD Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Bone Marrow
Hematopoietic Stem Cell Transplantation
Humans
Middle Aged
Mutation
Myelodysplastic Syndromes
Prognosis
Transplantation, Homologous