MYELODYSPLASTIC SYNDROMES IN THE ELDERLY - THE ROLE OF GROWTH-FACTORSIN MANAGEMENT

Myelodysplastic syndrome (MDS) comprises a group of heterogeneous clon al bone marrow disorders leading to peripheral cytopenia(s) and hyperc ellular marrow in the majority of the patients. The morphology of the cell lines is characterized by dysplastic features in some or all cell lines. The FAB classification has divided MDS in five subgroups, name ly (1) RA (refractory anemia); (2) BARS (refractory anemia with ring s ideroblasts); (3) CMML (chronic myelomonocytic leukemia); (4) RAEB (re fractory anemia with excess blasts); and (5) RAEB-T (refractory anemia with excess blasts in transformation). Myelodysplastic syndrome remai ns primarily a disease of the elderly. With a reported median age of 7 4.4 years, patients have a chronic relentless course with complication of cytopenias, and a significant number of MDS patients, especially f rom the RAEB and RAEB-T categories, end up in acute myeloid leukemic t ransformation. Cytogenetic abnormalities are present in 40-58% of the cases and can provide not only help in diagnosis, but also understandi ng regarding the clinical course and prognostic aspect. Management of MDS is quite pragmatic and at this stage far from satisfactory. Variou s modalities have included use of differentiating agents, aggressive c hemotherapy, bone marrow transplant and, more recently, significant in terest has been generated in the use of hematopoietic growth factors. Differentiating agent trials have been unrewarding so far; chemotherap y trials have resulted in less benefit and more early toxic deaths, es pecially in the elderly MDS patients where the disease predominates. B one marrow transplant appears suitable for some patients who are at a younger age. Salvation from this disease is being searched in the prop er usage of hematopoietic growth factors and cytokines. There has been concern, however, that usage of growth factors has led to early and e nhanced transformation of these patients to frank acute leukemic state s. This concept appears to be somewhat refuted by newer controlled tri als with GM-CSF and G-CSF, emphasizing that the acute leukemic transfo rmation is the natural course of the disease and is not hastened by gr owth factor use. Preliminary studies are also suggesting that a combin ation of growth factors, especially G-CSF and erythropoietin as compar ed to chemotherapies, could be more beneficial in prolonging the survi val of MDS patients who have progressed to the acute leukemic phase. M ore studies are needed for the understanding of the pathogenetic mecha nism(s) in order to facilitate a more suitable and appropriate managem ent strategy for MDS. Copyright (C) 1996 Elsevier Science Ltd.