Epidemiology of myelodysplastic syndromes: many questions remain

Myelodysplastic syndromes (MDS) are a complex group of hematopoietic stem cell disorders with the epidemiology not completely understood and few large population-based studies to define the risk of MDS development or disease progression. Of the few studies identifying risk factors predicting the development of MDS, concurrent alcohol and tobacco use, autoimmune disorders [1], exposure to pesticides, insecticides, and coffee, and recurrent upper respiratory infections [2], as well as family history of hematopoietic cancer or exposure to agricultural chemicals, solvents, or tobacco [3], are noted risk factors. Once diagnosed with MDS, prognosis and risk of transformation to acute myelogenous leukemia (AML) are currently informed by the International Prognostic Scoring System (IPSS) [4] and the World Health Organization (WHO)-based Prognostic Scoring System (WPSS) [5]. It is currently accepted that MDS with a higher blast percentage, high-risk IPSS (INT-2 or high), and/or adverse karyotype has an increased risk of progression to AML [4]. However, large-scale study refining our understanding of additional patient, disease, and treatment variables on outcomes is lacking.

In this issue of Leukemia and Lymphoma, Mutetwa et al. describe their analysis of 214 unselected patients with MDS from the University of Pittsburgh Medical Center Network Cancer Registry in Western Pennsylvania [6]. The cohort consisted of patients with predominantly low (29.4%) and INT-1 (48.6%) IPSS scores, and the majority with WHO morphology of refractory anemia with excess blasts (RAEB; 35%) or MDS-unclassified (MDS-U; 42%). Their analysis investigated the impact of patient exposures and family history as well as MDS disease characteristics and treatment interventions on the risk of death or transformation to AML. The population exposure history was significant for smoking (62.6%), alcohol use (44.4%), or exposure to both (34%), with a striking family history of cancer (49%). Overall survival for the entire cohort was low, with 70% of patients deceased at 3 years.

Their analysis focused on characterizing specific variables that impacted both survival and progression to AML. Overall survival was not impacted by gender but was adversely affected by older age [7] and higher-risk MDS [4], and positively altered in patients who tolerated ≥3 sessions of chemotherapy. Increased risk of progression to AML correlated with a family history of cancer and higher blast percentage, whereas exposure to a higher number chemotherapy cycles was associated with a decreased risk of AML progression.

The authors' analysis identifies valuable specific patient characteristics, MDS disease biology characteristics, and treatment interventions that further define the chance of survival and risk of AML transformation of a patient with MDS. The poor overall survival in the population with relatively lower risk of MDS suggests that features not captured by the IPSS play a major role in risk of progression to AML or death. The significance of age and disease characteristics such as blast percentage or response to chemotherapy further highlight the role of patient features and disease biology that aid MDS epidemiologic prognostic guidance. Lastly, the correlation with a positive family history of malignancy raises the question of an underlying genetic susceptibility to developing MDS.

While predicting the overall survival and risk of progression to AML are important in studying MDS and directing clinical care, the study calls our attention to the paucity of data regarding modifiable risk factors for both the development of MDS and disease progression, and highlights the need for future study. To more fully understand the entirety of the myelodysplastic syndromes from risk of development to risk of AML progression, future large-scale prospective studies are warranted. Case-controlled cohort analysis of patients with MDS with age-matched controls detailing exposure, lifestyle, and medical histories, with long-term follow-up to define impact of treatment on disease natural history, will help to identify additional modifiable risk factors for the development of MDS as well as progression to AML. Inclusion of correlative genomic or epigenetic studies into prospective MDS trials is needed, and will provide invaluable data to correlate clinical prognosis with biologic features of the disease.

There has been considerable progress in understanding the clinical and biologic heterogeneity of myelodysplastic syndromes; however, further work is needed to comprehensively describe this complex spectrum of diseases.

Potential conflict of interest: A disclosure form provided by the author is available with the full text of this article at www.informahealthcare.com/lal.