Other characteristics

Other variables with prognostic value, but of lesser importance, include age (which reflects a poorer tolerance to cytopenia-associated complications and the impact of other comorbid conditions associated with older age rather than a more aggressive clinical course)79; FAB classification7; gender (worse prognosis for male patients, which may be explained to some extent by the greater life expectancy of women in industrialized countries)7; percentage of blasts in peripheral blood7; presence of immature myeloid precursors and nucleated RBCs in peripheral blood7; degree of multilineage dysplasia in RA and RARS (as in the recent World Health Organization [WHO] proposals of classification of MDS14)15-21; marrow basophilia or eosinophilia,22 serum lactate dehydrogenase (LDH) level (which may provide an indirect measure of ineffective hematopoiesis and leukemic burden)23; and some BM biopsy findings, such as abnormal location of immature myeloid precursors (ALIP), hypercellularity, and fibrosis.5 6 24 Other characteristics, such as serum p-2-microglobulin level,25 in vitro growth pattern of granulocyte-macrophage progenitors,26 plasma soluble interleukin 2 receptor level,27 plasma levels of soluble vascular endothelial growth factor receptor 1,28 and magnetic resonance imaging pattern29 have been also implicated in MDS prognosis. Several flow cytometry parameters have been shown to influence the outcome of disease,30 including the expression of CD7, CD10, and CD15 by BM blasts,31 and the number of CD34-positive cells in the peripheral blood.32 A prognostic scoring system based exclusively on flow cytometry data has been reported to predict the outcome after allogeneic stem cell transplantation.33

The recent progress in understanding the biology of MDS has led to studies of new prognostic parameters to predict outcome. A greater degree of apoptosis in the BM, as measured by different techniques, has been associated with longer survival and time to develop AML.34-45 Mutations of ras, fms, and p53 genes, which reflect genomic instability, occur more frequently in patients with poor prognosis and are associated with shorter survival and a higher risk of leukemia.46 47 The level of expression of WT1, measured by real-time quantitative polymerase chain reaction (PCR), has a strong direct relationship with the percentage of blasts in the BM and the presence of chromosomal abnormalities.48 Telomere stability, another marker of genomic instability, is frequently impaired in high-risk MDS. Patients with shortened terminal restriction fragments, measured by the PCR-based twin reversed arterial perfusion assay, have a significantly lower hemoglobin level, higher percentage of BM blasts, higher incidence of cytogenetic abnormalities, and a higher risk of leukemic transfor-mation.37 The incidence of inactivation by methyla-tion of the p15 gene is higher in patients with >10% BM blasts and increases with progression to AML.4950 Preliminary evidence suggests that gene profiling could also have prognostic value in MDS patients.5152 Information on the prognostic relevance of these new biological factors, however, is still scarce. Further studies that include a larger number of cases and multi-variate analyses are needed before this evidence can be accepted and used in the clinical management of patients.

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