Using Gender to Improve Prognostication and Decision-Making in Myelodysplastic Syndromes

A mounting body of evidence shows that gender plays an essential role in many facets of myriad diseases, such as risk factors, pathophysiology, clinical presentation, symptoms, prognosis, and response to therapy. More and more, gender is being considered in clinical decisions.

A study presented at the 62nd ASH Annual Meeting & Exposition shed light on how the variable of gender may be considered to improve prognostication, decision-making, and personalized treatment in patients with myelodysplastic syndromes (MDS).

“In MDS, sex captures additional prognostic information at the individual patient level, possibly reflecting a different molecular background and, most importantly, a sex-specific interaction between disease-related factors and comorbidity,” according to the researchers, led by Giulia Maggioni, MD, of the Cancer Center at IRCCS Humanitas Research Hospital and Humanitas University, Milan, Italy. “Our results strengthen the rationale to include sex in personalized prognostic assessment in these diseases.”

The research group pulled data on 11,878 patients from three registries. They analyzed associations between gender and several clinical, biological, and genetic disease-specific factors, finding that:

  • Women more often had single-lineage dysplasia and MDS with del(5q). Men more often had multilineage dysplasia and excess blasts.
  • Men had lower rates of overall survival than women. Gender was a significant prognostic indicator, even in multivariable analysis.
  • Patients with early-stage disease had a higher risk of death from non-leukemic causes. Specifically, men had higher rates of cardiac comorbidity and death, especially when hemoglobin level was <10 g/dL. The study team noted, “Sex may capture prognostic information on the detrimental interactions between anemia and cardiac comorbidity.”

In analyses of genetic factors, the researchers found that:

  • Men had a higher prevalence of mutations in 47 MDS-associated genes, as well as more co-mutations. Splicing factor mutations also were more common in men compared with women.
  • In patients with MDS with ring sideroblasts, SF3B1was mutated in almost all female patients (95% of mutated cases). SRSF2 and ZRSR2 mutations were present in 26% of mutated cases in men.
  • In addition, men had more mutations in DNA methylation genes. In contrast, women more often had mutations in tumor suppressor genes.