New Tool to Optimize Treatment for Myelodysplastic Syndrome Patients

In a significant advance for the treatment of myelodysplastic syndromes, an international team of researchers has developed and validated a groundbreaking decision support system (DSS). This new tool aims to determine the optimal timing for allogeneic hematopoietic stem-cell transplantation (HSCT) based on a combination of clinical and genomic data. Dr. Francesc Solé and Dr. Blanca Xicoy, researchers from the Josep Carreras Institute, are part of the international MDS working group behind the research.

New Tool to Optimize Treatment for Myelodysplastic Syndrome Patients
New Tool to Optimize Treatment for Myelodysplastic Syndrome Patients

Under the term Myelodysplastic Syndromes (MDS) hides a group of disorders caused by poorly formed or dysfunctional blood cells, often leading to severe anaemia, infection risks, and a higher likelihood of developing acute myeloid leukaemia. Hematopoietic stem-cell transplantation (HSCT) is the only potentially curative treatment for MDS, but the procedure's success heavily depends on its timing and the patient's condition at the time of transplantation.

The research, published in the Journal of Clinical Oncology, addresses the critical issue of timing for HSCT. The team, led by Dr. Cristina Astrid Tentori and colleagues from various prestigious institutions, including Dr. Francesc Solé and Dr. Blanca Xicoy, from the Josep Carreras Leukaemia Research Institute, utilized the Molecular International Prognostic Scoring System (IPSS-M), which includes both clinical features and genetic mutations, to enhance decision-making for MDS treatment.

The study analysed a retrospective cohort of 7,118 patients with MDS. These patients were stratified into training and validation cohorts to build and test the Decision Support System (DSS). The tool estimates average survival over an eight-year period for various combinations of clinical and genomic factor and determines the optimal timing for HSCT by comparing different treatment strategies.

The results after using the DSS showed that patients with low and moderate-low risk profiles, as determined by IPSS-M, would benefit from a delayed transplantation strategy. In contrast, those classified as moderately high, high, or very high risk should undergo immediate transplantation to maximize life expectancy, according to the predictions of the new tool.

If the accuracy of the new system is confirmed, something that would need further analysis, its use could significantly improve the current Revised International Prognostic Scoring System (IPSS-R). According to the findings, 15% of patients who would be recommended for immediate transplantation under IPSS-R would rather benefit more from a delayed approach when using the IPSS-M based policy. Conversely, 19% of patients advised to delay transplantation under IPSS-R should actually receive immediate HSCT according to the IPSS-M assessment.

Clinical Relevance

The inclusion of genomic data in the IPSS-M provides a more personalized approach to MDS treatment. This is particularly important as MDS exhibits a high degree of clinical and genetic heterogeneity, which the conventional IPSS-R does not fully capture. The new model allows for more precise risk stratification and treatment planning, potentially improving patient outcomes significantly.

Dr. Tentori and her team highlighted the importance of integrating genomic information into clinical practice, emphasizing that the DSS could change the transplantation policy for about 17% of patients. This shift underscores the clinical relevance of genetic screening in the treatment of MDS and supports a move towards more individualized therapy plans.

While the DSS represents a significant step forward, its implementation faces challenges, particularly in regions where molecular testing is not routine due to cost and infrastructure limitations. To address this, the researchers have identified a minimum set of 15 critical genes that provide high predictive accuracy, potentially making the system more accessible in diverse clinical settings.

Overall, this innovative DSS marks a major advancement in the management of MDS, promising to optimize treatment strategies and improve patient survival by tailoring decisions to the unique clinical and genetic profile of each patient. As the medical community continues to embrace precision medicine, tools like this DSS will play an increasingly crucial role in improving outcomes for patients with complex diseases like MDS.