Clinical-genomic profiling of MDS to inform allo-HSCT:Recommendations from an international panel on behalf of the EBMT

Blood. 2025 Feb 19:blood.2024025131. doi: 10.1182/blood.2024025131. Online ahead of print.

ABSTRACT

For patients with myelodysplastic neoplasm/syndrome (MDS), allogeneic hematopoietic cell transplantation (allo-HCT) represents the only potentially curative treatment, capable of eradicating disease-related mutant hematopoietic cells and establishing normal donor hematopoiesis. Biologic-assignment clinical trials have indicated that in eligible patients, allo-HCT is associated with superior clinical outcomes compared to non-transplant therapy. However, this therapeutic option is only available to a subset of patients, and the outcome is influenced by multiple factors inherent to the patient, the MDS subtype, and the allo-HCT procedure itself. In 2017, the EBMT published recommendations for allo-HCT in MDS to guide practical decision-making. In the contemporary era, genomic profiling has become routine clinical practice in many centers, and the most recent classification systems include MDS entities that are defined by genetic abnormalities. In particular, the Molecular International Prognostic Scoring System (IPSS-M) offers more precise prognostication across all clinical endpoints and currently represents the standard tool for estimating patient survival in the absence of disease-modifying treatment. Evidence from multiple sources increasingly indicates that allo-HCT should be considered at the time of diagnosis in all eligible MDS patients. Therefore, genomic profiling for somatic mutations and testing for germline predisposition variants are integral to determining a patient’s eligibility for transplantation. While all patients with higher-risk MDS are potential candidates for immediate transplantation, a subset of those with lower-risk MDS may also derive benefit from this procedure at an earlier disease stage. Comprehensive recommendations on behalf of an expert international panel for clinical practice and future clinical studies of relevance are presented.

PMID:39970324 | DOI:10.1182/blood.2024025131