Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for progression, suggest that myelodysplastic syndromes encompass a multitude of disorders, likely involving numerous pathologic pathways. In fact, it is the effort to understand the underlying biology of these syndromes that has led to recent advances in treatment approaches, including the FDA approval of three new agents (5-azacitidine, decitabine, and lenalidomide) for the treatment of MDS. This review will present data supporting each of the current pathophysiologic pathways implicated in the development and progression of MDS; summarize the emerging clinical paradigms for treating patients with MDS; and offer insights into several novel approaches attempting to improve treatment options for future MDS patients.

Factors associated with hematopoietic cell transplantation (HCT) among patients in a population-based study of myelodysplastic syndrome (MDS) in Minnesota

“…These agents can alter the disease course, improve survival and in some cases serve as a bridge to HCT. 11–15 Choice of a treatment strategy depends on a number of factors, but most employ a risk based treatment approach based on the IPSS risk stratification. Survival in patients with untreated intermediate 2 or high-risk disease is generally less than a year so modifying the disease course and avoiding progression to acute leukemia are often the goals.…”

Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy

“…[1][2][3] Cytogenetic abnormalities are found in approximately one-half of newly diagnosed cases. 4,5 Prognosis is estimated by the International Prognostic Scoring System (IPSS) with 4 risk groups (low, intermediate-1, intermediate-2, and high) for disease progression to AML, 6 and median survival ranges from 5.7 years in low-risk MDS to 0.4 years in high-risk MDS.…”

Usefulness of Magnetic Resonance Imaging as a Prognostic Variable in Myelodysplastic Syndromes

“…Cytostatic drugs such as alkylating, topoisomerase II inhibitors, purine analogues, and hydroxycarbamides, as well as physical factors in the form of ionizing radiation, may also cause the disease [12,13]. The studies confirmed cases of disease occurrence among family members [14,15].…”

“…Factors contributing to the occurrence of myelodysplastic syndrome are numerous chemical substances like benzene, toluene, herbicides, pesticides, tobacco smoke, hair dyes, silica fume, and heavy metal compounds [12,13]. Cytostatic drugs such as alkylating, topoisomerase II inhibitors, purine analogues, and hydroxycarbamides, as well as physical factors in the form of ionizing radiation, may also cause the disease [12,13].…”