According to the World Health Organization, myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders. With MDS, an individual’s bone marrow does not produce enough healthy blood cells, resulting in fewer than normal mature blood cells circulating in the body. Most patients with MDS are elderly, with a median age of 70 years, and typically present with complications associated with peripheral blood cytopenias. The clinical course of MDS is extremely variable, which makes accurate prognostic assessment critical.
In a recent analysis published in Mayo Clinic Proceedings, Mayo Clinic shared its decade’s worth of experience with 1,000 consecutive MDS patients who were evaluated at Mayo Clinic, with the following main objectives:
- To provide a comprehensive description of clinical, laboratory, and morphological characteristics at diagnosis.
- To validate prognostic factors predictive of survival and evolution to acute leukemia followed by the application of currently available prognostic scoring systems.
- To compare clinical characteristics and survival of patients diagnosed before and after 2005.
“The clinical heterogeneity of MDS with an extremely variable risk of disease transformation to acute myeloid leukemia explains the variation observed in survival, ranging from only a few months to almost a decade,” said Naseema Gangat, M.B.B.S., Consultant in the Division of Hematology and lead author on this review. “Given the variable course of the disease, treatment options can range significantly from supportive care to disease-modifying therapy and allogeneic bone marrow transplant.”
A total of 1,000 consecutive patients with primary MDS were considered during the review, including 531 patients diagnosed before 2005 and 469 diagnosed after 2005. The year 2005 was chosen as the cutoff year for analysis to coincide with the approval of the hypomethylating agent azacitidine in 2004 followed by the immunomodulatory agent lenalidomide for the treatment of MDS with del(5q).
The study included four commonly used prognostic scoring systems for risk stratification: Revised International Prognostic Scoring System (IPSS-R), MD Anderson Score (MDAS), World Health Organization Prognostic Scoring System (WPSS), and International Prognostic Scoring System (IPSS).
Median survival and leukemic transformation rates were similar in MDS patients diagnosed before or after 2005, despite the significantly higher use of hypomethylating agents in the latter group. The analysis also successfully validated each of the four scoring systems (IPSS, IPSS-R, WPSS, and MDAS), showing an effective discrimination among the different risk groups, with median survival ranging from more than five years for low-risk patients to less than six months for high-risk patients.
“A major strength of our study is the relatively long and mature median follow-up period of 27 months, during which time 808 deaths and 129 leukemic transformations were documented,” said Dr. Gangat. “This enabled us to provide an accurate comparison of survival patterns between the two groups.”
Further, the poor outcome in patients with MDS does not appear to have improved over time, despite many of these patients having received disease-modifying therapy including allogeneic transplant.
“Our analysis shows that current risk-stratification systems for MDS are not substantially different from each other,” said Dr. Gangat. “Based on our results, there is a dire need for drugs that are truly disease-modifying and risk models that incorporate prognostically relevant mutations.”
To date, this is the largest series of patients with primary MDS to be evaluated at a single institution, reinforcing the uniformity of both diagnostic and therapeutic interventions.
“As we begin to unravel the biology of MDS and evaluate novel therapies, it will provide a framework for future studies involving molecular risk stratification, genotype-phenotype correlations, and genetic determinants of response to therapy,” added Dr. Gangat.
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