The myelodysplastic syndromes (MDS) are a diverse group of acquired clonal hematopoietic disorders most common in older patients presenting with cytopenias, qualitative abnormalities of marrow cell maturation and progression to acute myelogenous leukemia. Abnormal proliferation and increased apoptosis of marrow precursors, the latter perhaps mediated by T-cell cytokine production, have been shown to play a role in the pathogenesis of these disorders. The main features determining the quality of life and prognosis of these patients are the frequency of red cell transfusion dependency and the increased incidence of transformation into acute myelogenous leukemia. The only curative treatment for these disorders is allogeneic marrow transplantation, a treatment associated with significant morbidity and available only to a limited number of patients. Nine promising new treatments reported over the last 3 years are reviewed in this article. 5-azacytidine, a cytidine analog which inhibits DNA proliferation and DNA methylation, significantly decreased red cell transfusion dependency, and decreased the frequency of transformation into acute leukemia with an associated improvement in quality of lift in reported phase II and phase III trials. Antithymocyte globulin (ATG) is active in patients with refractory anemia, with long lasting remissions and documented responses leading to red cell transfusion independence. Amifostine, a cytoprotective agent, has clearly demonstrated hematopoietic effects in MDS but responses have not been significant enough to lead to red cell transfusion independence. Other promising treatments reviewed in this article include: 1. combinations of GCSF and erythropoietin; 2, combinations of pentoxifylline, ciprofloxacin, dexamethasone (PCD); 3. decitabine; 4. topotecan; 5. high dose chemotherapy with autologous peripheral stem cell rescue and 6. non-myeloablative allogeneic peripheral stem cell transplants.
|Original language||English (US)|
|Number of pages||8|
|Journal||Cancer Research Therapy and Control|
|State||Published - 1999|
ASJC Scopus subject areas
- Cancer Research