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.

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 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 mutations were classified as 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 (28% 29%; = .89), (23% 29%; = .37), and (16% 16%; = .99) being most common. OS in patients with a mutation was worse compared with patients without mutation (21% ± 5% [SE] 52% ± 4% at 3 years; < .001). Among those with a mutation, OS was similar between versus (22% ± 8% 20% ± 6% at 3 years; = .31). Considering HCT as a time-dependent covariate, patients with a mutation who underwent HCT had improved OS compared with non-HCT treatment (OS at 3 years: 23% ± 7% 11% ± 7%; = .04), associated with a hazard ratio of 3.89; 95% CI, 1.87 to 8.12; < .001 after adjustment for covariates. OS among patients with molecular IPSS (IPSS-M) very high risk without a mutation was significantly improved if they had a donor (68% ± 10% 0% ± 12% at 3 years; = .001).

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