Updated EBMT transplant guidelines for MDS highlight use of genomic profiling

September 2025

For patients with myelodysplastic syndromes (MDS), allogeneic hematopoietic cell transplantation (alloHCT) represents the only potentially curative treatment. Evidence from multiple sources increasingly indicates that alloHCT should be considered at the time of diagnosis in all eligible patients with MDS. A team of subject matter experts from the European Society for Blood and Marrow Transplantation (EBMT) performed a systematic review of recent literature to issue an update to their 2017 guidelines, emphasizing the importance of genomic profiling to inform alloHCT eligibility.

Background

Since 2017, significant advances in understanding and integrating genomic information into clinical decision-making for MDS have prompted a need to update recommendations. These advances include movement towards routine use of genomic profiling to aid in diagnosis and risk stratification. The recently developed Molecular International Prognostic Scoring System (IPSS-M) incorporates both clinical and genomic features for risk stratification at the individual patient level and updates the 2012 Revised International Prognostic Scoring system (IPSS-R).

Methods

The MDS subcommittee of the Chronic Malignancies Working Party of the EBMT conducted a systematic literature review and developed questions on key topics relevant to clinical decision-making in the transplant setting. Key themes explored in the literature search and development of guidelines included:

  • Identifying effective MDS risk assessment strategies based on genomic information (IPSS-M)
  • Patient eligibility at time of diagnosis based on disease and patient-related risk factors
  • Timing of alloHCT

Results

The updated recommendations for alloHCT in MDS emphasize that:

  • All patients with higher-risk MDS as defined by the IPSS-M should be considered potential candidates for immediate alloHCT. A subset of patients with lower-risk MDS may also benefit from alloHCT at an earlier stage of the disease.
  • AlloHCT eligibility should be assessed at the time of diagnosis.
  • Evaluation of MDS risk requires calculation of the IPSS-M score, taking into account conventional cytogenetics, genomic profiling and TP53 allelic state.

The complete set of recommendations is summarized below:

Key item
Recommendation / Consideration
Transplantation eligibility based on disease-related risk factors
  • Transplant timing in MDS should be guided by disease-related risk, primarily using IPSS-M
  • Higher-risk patients are candidates for immediate alloHCT, while lower-risk cases require individualized evaluation, especially if there are adverse features like germline predisposition or treatment-refractory cytopenias
Donor selection
  • HLA-matched relatives, matched unrelated donors and haploidentical donors can be used for patients with MDS undergoing alloHCT, with a preference for younger donors in the selection algorithm
Patient-informed decision making
  • Counseling for alloHCT in MDS should begin at diagnosis and focus on helping patients make informed choices aligned with their personal goals and quality of life considerations
  • Early involvement of the transplant physician is essential for timely donor planning and meaningful discussions
Timing of transplantation
  • Immediate alloHCT is generally more beneficial for patients with higher-risk MDS (according to IPSS-M), while delayed transplantation may extend survival in lower-risk patients, particularly those under the age of 60
Choice of conditioning regimen and GVHD prophylaxis
  • Treosulfan-based regimens show comparable outcomes to busulfan and may be most effective as reduced intensity conditioning, though its intensity classification remains unclear
  • Expert consensus on conditioning regimens and GVHD prophylaxis strategies is lacking
Post-transplantation
  • Measurable residual disease (MRD) assessment is recommended after alloHCT regardless of MDS risk
  • Post-transplant therapeutic strategies for patients with MRD or relapsed patients include treatment with hypomethylating agents and donor lymphocyte infusion

Key takeaways

These comprehensive recommendations clarify transplant timing, donor selection and risk assessment for patients with MDS. Genomic profiling via IPSS-M will aid in identifying suitable candidates for alloHCT and understanding optimal timing. Incorporating these recommendations into the existing treatment paradigm could expand the number of MDS patients who are potential candidates for alloHCT.

Gurnari C, et al., published in Blood

Additional resource

View additional guidance from NMDPSM and CIBMTR® on donor search and selection strategies in alloHCT.