Myelodysplastic syndromes (MDS) are clonal disorders of the multipotent hematopoietic stem cell characterized by ineffective hematopoiesis and associated with marrow hypercellularity, increased intramedullary cell death and peripheral cytopenias of varying severity. Patients with myelodysplasia have a propensity (20% to 30% of cases) to undergo transformation into acute myeloid leakemia (AML), and a large body of evidence indicates that MDS represent steps in the multiphasic evolution of AML. Progression of the disease is characterized by expansion of the abnormal clone and inhibition of normal hematopoiesis leading to deterioration of the blood cell count and/or development of AML. MDS are relatively unusual in childhood, representing only 3% of pediatric hematological malignancies, although it has been reported that up to 17% of pediatric AML cases may have a previous myelodysplastic phase. The first systematic attempt at morphological classification of MDS was provided by the French-American-British (FAB) group. However, the FAB classification of MDS is only partially applicable in children. Some variants are extremely rare or absent (refractory anemia with ring sideroblasts and chronic myelomonocytic leukemia), and other peculiar pediatric disorders, represented by juvenile chronic myelogenous leukemia (JCML) and the monosomy 7 syndrome, are not included. Moreover, since there is a partial overlap between pediatric MDS and myeloproliferative disorders and the variants occurring in young children have rather specific features, some confusion still surrounds the nosographical definition of childhood MDS, so that none of the proposed classifications are widely accepted and used. Characteristically, some genetic conditions such as Fanconi's anemia, Shwachman's and Down's syndromes predispose to the development of MDS in childhood. The most common variants of childhood MDS are represented by JCML and the monosomy 7 syndrome, both disorders typically occurring in young children. JCML is characterized by a spontaneous growth of granulocyte-macrophage progenitors that show a striking hypersensitivity to granulocyte-macrophage colony-stimulating factor. Clinical presentation resembles that of some myeloproliferative disorders, with massive organomegaly usually not observed in the classically reported variants of MDS. Clinical features of the monosomy 7 syndrome resemble those observed in JCML and a differential diagnosis between these two entities relies upon the higher percentage of fetal hemoglobin, the more pronounced decrease in platelet count and, in some cases, the lack of the peculiar cytogenetic abnormality in the latter. With the number of children being cured of cancer constantly rising, a significant increase in secondary or chemotherapy-related myelodysplasia is being observed, and these disorders represent a formidable challenge for pediatric hematologists due to their poor response to chemotherapy. As a matter of fact, owing to their biological heterogeneity and aggressive clinical course in childhood, all MDS variants pose serious difficulties for successful management. If a compatible donor is available, allogeneic bone marrow transplantation (BMT) becomes the treatment of choice and should be performed during the early stages of the disease. Supportive therapy, differentiative treatments and low-dose chemotherapy, while valuable alternative therapeutic options in adults, have limited application in pediatric patients. The role of intensive chemotherapy and autologous BMT has not yet been clearly defined, and the use of hematopoietic growth factors does not seem to have a significant influence on the natural history of the disease. In the future, new insights into the events leading to progressive genetic changes in the clonal population and into the molecular basis of these genetic lesions could result in interesting new therapeutic approaches directed either at the oncogenes involved in the pathogenesis of the disease, or at the cytokines and/or their receptors causing the abnormal differentiation and proliferation of the myelodysplastic clone.
|Number of pages||12|
|Publication status||Published - 1995|
- bone marrow transplantation
- juvenile chronic myelogenous leukemia
- monosomy 7
- myelodysplastic syndromes
ASJC Scopus subject areas