MDS refers to a very heterogeneous group of myeloid malignancies arising from abnormal stem cell function, immune deregulation, and multiple genomic events. Historically, MDS was categorized as higher and lower risk according to the International Prognostic Scoring System (IPSS), based mainly on the percentage of blasts but also considering the number of cytopenias and cytogenetics. Subsequently, a more robust version of this scoring system was developed, the Revised International Prognostic Scoring System (IPSS-R), which has become the standard. Both the IPSS and the IPSS-R were developed in a specific patient subset: newly diagnosed patients at the time of initial presentation. The IPSS-R categorizes patients into 1 of 5 groups, ranging from very low risk to very high risk. A newer molecular IPSS is anticipated that would include a sophisticated molecular genetic analysis and, of course, cytogenetic information.

In general, we currently identify patients with higher-risk MDS as those with either a higher percentage of blasts (eg, >10%) or poor-/high-risk cytogenetic alterations. Increasingly, we are beginning to use specific genomic lesions (eg, TP53 mutations) and to consider the number of mutations (eg, ≥3) to inform the prognosis in patients with MDS. Many of the individuals who have very high-risk disease have complex karyotype and a number of them may have high-risk mutations, such as TP53. These patients tend to have a specific prognosis; for instance, those with TP53 mutation have a very high rate of relapse post transplantation.

However, treatment decisions draw on many other factors, in addition to the IPSS-R and genomic lesions, such as patient age and comorbidities. So, to generalize, younger patients (eg, ≤65 years of age) with more benign cytogenetic/molecular alterations might be more likely to be treated with a high-intensity program as if they had acute myeloid leukemia. In contrast, older patients with higher-risk disease might be treated with a lower-intensity approach, such as either azacitidine or decitabine as a single agent or perhaps with a clinical trial protocol involving combination therapy. We often include clinical trial participation in our discussions with such patients, in hopes of improving their outcomes with the standard of care.

In summary, when I discuss treatment options with my patients, I consider their age, comorbidities, cytogenetics, and molecular profile. By putting this all together, we can determine which therapies or investigational options might be best for them.