Clinical Characteristics, Molecular Features and Transplantation Outcomes in MDS with Low Blasts and without Defining Genetic Abnormalities: An Analysis of MDS-h and MDS-LB Patients

Objective: According to the World Health Organization (WHO) 2022 classification, myelodysplastic neoplasms/syndromes (MDS) patients without increased blasts and defining genetic abnormalities are categorized as either hypoplastic MDS (MDS-h) or MDS with low blasts (MDS-LB). This study aims to evaluate the clinical characteristics, genetic and cytogenetic profiles, and outcomes of MDS-h and MDS-LB patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: We retrospectively analyzed data from 25 MDS-h and 64 MDS-LB patients who underwent allo-HSCT between January 2010 and January 2023. A one-to-one propensity score-matched analysis was performed to minimize confounding factors. Additionally, genetic mutations and chromosomal abnormalities were compared among 25 MDS-h, 64 MDS-LB and 205 severe aplastic anemia (SAA) patients.

Results: Most patients were classified into higher-risk group by Molecular International Prognostic Scoring System (IPSS-M) (MDS-h: 80.00% vs. MDS-LB: 71.88%, P=0.605). Pre-transplantation transfusion dependency was observed in 80.0% of MDS-h and 79.7% of MDS-LB patients (P=0.541). MDS-h patients had lower platelet counts (35×10⁹/L vs. 59×10⁹/L, P=0.034) and a higher incidence of severe cytopenia (56.00% vs. 34.38%, P=0.104). Both MDS-h and MDS-LB patients exhibited significantly more mutations and chromosomal abnormalities compared to SAA patients (P<0.030). BCOR mutations were prevalent in MDS-h (23.81%), while U2AF1 (39.62%), ASXL1 (30.19%) and RUNX1 (20.75%) mutations were common in MDS-LB. The estimated 3-year overall survival (OS) was 76.0% (61.0%-94.7%) for MDS-h and 83.9% (75.2%-93.6%) for MDS-LB (P=0.328). Failure-free survival, transplant-related mortality and cumulative incidences of engraftment, graft-versus-host disease and infection were also similar between groups. Risk factors for worse OS included bloodstream infection within 100 days post-HSCT and FAT1 mutations in MDS-h, and RUNX1 mutations in MDS-LB. Donor type and the interval from diagnosis to HSCT had no significant impact on post-HSCT outcomes.

Conclusions: MDS-h and MDS-LB patients undergoing allo-HSCT exhibited slightly distinct clinical and genetic features, but both groups achieved favorable outcomes after transplantation. This study highlights the potential efficacy of allo-HSCT in mitigating adverse genetic mutations in MDS-h and MDS-LB patients, with no significant impact from donor type or diagnosis-to-HSCT interval on outcomes.

No relevant conflicts of interest to declare.