The following is a summary of “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,” published in the October 2023 issue of Oncology by Versluis, et al.
For a study, researchers sought to assess the impact of genetic mutations associated with myelodysplastic syndrome (MDS) on the effectiveness of allogeneic hematopoietic cell transplantation (HCT) in improving overall survival (OS) among MDS patients.
The study involved 309 MDS patients aged 50 to 75 years who had intermediate-2 or high-risk MDS, according to the International Prognostic Scoring System (IPSS). The patients were enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study. Targeted sequencing was performed to analyze the presence of specific gene mutations in these patients. The study then assessed the association between these gene mutations and OS. In particular, patients with TP53 mutations were categorized as TP53single if they had a single altered allele (via point mutation, deletion, or copy-neutral loss of heterozygosity) or TP53multihit if both alleles were altered.
The distribution of gene mutations was similar between the group of patients who had donors available for transplantation (donor arm) and those who did not (no donor arm). The most common mutations were TP53 (28% vs. 29%), ASXL1 (23% vs. 29%), and SRSF2 (16% vs. 16%). Patients with TP53 mutations had significantly worse OS compared to patients without TP53 mutations (21% ± 5% [SE] vs. 52% ± 4% at 3 years; P < .001). Among patients with TP53 mutations, there was no significant difference in OS between TP53single versus TP53single (22% ± 8% vs. 20% ± 6% at 3 years; P = .31). When considering HCT as a time-dependent factor, patients with a TP53 mutation who underwent HCT had improved OS compared with non-HCT treatment (OS at 3 years: 23% ± 7% vs. 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% vs. 0% ± 12% at 3 years; P = .001).
HCT enhanced OS in patients with TP53 mutations, regardless of whether they had single or multihit TP53 mutations. Moreover, patients categorized as very high risk based on molecular IPSS (IPSS-M) without TP53 mutations experienced improved outcomes when a suitable donor was accessible. The study underscored the potential benefits of HCT in MDS patients with specific genetic mutations and highlighted the importance of donor availability in improving survival outcomes.