Myelodysplastic Syndromes (MDS) are a heterogeneous group of blood malignancies that can develop into Acute Leukemias if not properly treated. Up until now, patient stratification relied mostly on direct observation of tissue samples under the microscope (cell morphology and chromosome alterations) by highly trained professionals, not considering valuable genetic information from both the patient and the disease.

However, genetic profiling of patients and tumors have become increasingly available in the last few years, especially in wealthy countries, and the window of opportunity to use this information in the clinic has widened. It is well known that most of the heterogeneity of MDS are due to genetic differences among people, as well as the particular set of alterations of a given tumor. Therefore, incorporating this information in the risk assessment, where available, feels just right.

Dr. Francesc Solé, who participated in the study, is confident that “this is the base to apply massive gene sequencing to MDS, to better define its prognosis and treatment” and, beyond this, he is confident that “while this study involved MDS only, it will open the door to applying the same strategy to other hematological or solid tumors in the future”.

The international research team was coordinated by the Papaemmanuil Lab at the Memorial Sloan Kettering Cancer Center (MSK) in New York and collected a total of 2,957 patient samples from 24 centers from 13 countries. Those samples were then sequenced by the Integrated Genomics Operation at MSK and analyzed in the Papaemmanuil laboratory. Another 754 samples derived from a Japanese MDS consortium were used to confirm the validity of their initial findings.

The integration of the results yielded the new IPSS-M, a new patient stratification system with six risk degrees, from very low to very high. Compared to the previous scoring system, roughly 1 in 2 patients (46%) were assigned to a different risk category when using the new IPSS-M, meaning that their treatment recommendations would have changed as well, usually for better. By using the six-degree scale, clinicians can recommend supportive therapy for those patients at lower risk, avoiding the toxicity of heavy chemotherapy, and a stronger drug prescription for the ones under a higher risk.

The researchers stressed that this new scoring system is born to be widely used as a diagnostic and prognostic tool, since the preliminary tests showed the IPSS-M could outperform the previous IPSS-R. However, the debate remains whether adopting costly and sophisticated international standards, not widespread available, could leave patients in low-income countries behind. Dr. Solé and Dr. Mallo discussed about it last February after an opinion paper published at the journal Blood by a panel of top experts in cytogenetics.

Beyond ongoing debates, though, it is undeniable that the new IPSS-M have the potential to revolutionize how clinicians assess the risk of an MDS to progress to an acute leukemia and prescript better therapies to their patients, to help them fight the disease and with the less possible toxic side-effects.

Reference article:

Elsa Bernard, Ph.D., Heinz Tuechler et al. “Molecular International Prognostic Scoring System for Myelodysplastic Syndromes”. NEJM Evidence 12 Jun 2022, Epub 12 Jun 2022. https://doi.org/10.1056/EVIDoa2200008