Treatment and prognostic factors in myelodysplastic syndromes

The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal bone marrow failure syndromes, characterized by different levels of uncoupling of proliferative and differentiative responses of haematopoietic stem cells, leading to progressive cytopenias, qualitative abnormalities in erythroid, granulocytic and megakaryocytic series, and increased transformation into acute leukaemia. The overall incidence rates are estimated to be around 3 to 5/100 000 per year, but in the age group over 70 years the incidence may rise as high as 15/100 000 per year (Aul et al, 1992a; Williamson et al, 1994; Radlund et al, 1995). Whether the incidence of MDS is rising-possibly in relation to environmental factors-is a matter of much debate. Undoubtedly the diagnostic possibilities and the investigative efforts have increased, but a true, steady increase cannot be denied (Reizenstein and Dabrowski, 1991). While most authors will agree on a dynamic multistep hypothesis in the pathogenesis of MDS, the true nature of the primary malignant cell is still unknown. Molecular studies have convincingly demonstrated clonal involvement of all myeloid lineages, but not uniformly of T- or B-lymphocytes, thereby challenging the concept of MDS as a true pluripotent stem-cell disorder. The advent of more refined stem cell isolation and purification techniques (e.g. multiparametric Facs-sort), of improved histopathological techniques (e.g. FISH), of more efficient long term culture techniques and of PCR technology for the evaluation of (proto)-oncogene involvement, will allow for a better understanding of the basic biological processes underlying MDS, for more accurate risk assessment and individualized treatment schemes. Therapeutic strategies in MDS have historically been inspired by either 'missionary' approaches, i.e. converting malignant cells into normal behaviour, or by 'crusader' tactics, i.e. destroying non-compliant elements at the expense of innocent bystanders (Boogaerts, 1989). Transplantation of haematopoietic stem cells has thereby proven to be the only truly curative treatment option, at least for younger patients. Whether any of the new cytokine combinations or differentiation inducers will improve at least the quality, possibly also the quantity of life of MDS patients, remains to be proven.