Accumulating evidence has shown that marrow failure in some patients with myelodysplastic syndrome is associated with autoimmunity, T-cell mediated myelosuppression and cytokine-induced cytopenias. In this perspective article, Drs. Barrett and Sloand expound on auto-immunity in myelodysplastic syndromes, in particular focusing on what has been learned from study of patients with trisomy 8. See ...

We performed a phase I/Il study of the administration of recombinant human granulocyte-macrophage colonystimulating factor (GM-CSF) to patients with aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 to 480 .tg/m2 were administered as a one-hour or fourhour intravenous infusion daily for 7 days or as a 1 2-hour infusion for 1 4 days. Temporary improvements were seen in granulocy...

Tumor-necrosis factor alpha activity has been correlated to ineffective erythropoiesis in lower risk myelodysplastic syndromes. Infliximab (Remicade(®)) is an anti-tumor necrosis factor alpha chimeric antibody that is used in the treatment of patients with rheumatoid arthritis or Crohn's disease. Forty-six patients with myelodysplastic syndromes and a relatively low risk of developing acute leu...

The immune states of 52 patients with myelodysplastic syndromes classified according to the FAB criteria were studied. Serum electrophoresis and immunoelectrophoresis, direct Coombs test, and tests for organ and non-organ specific antibodies were performed. Twenty six patients had immunoglobulin abnormalities: six (11.5%) had monoclonal gammopathy; 17 (32.6%) had polyclonal increases in serum i...

PURPOSE The clinical efficacy, different dosages, treatment schedules, and safety of azacitidine are reviewed. SUMMARY Azacitidine is the first drug FDA-approved for the treatment of myelodysplastic syndromes that has demonstrated improvements in overall survival and delaying time to progression to acute myelogenous leukemia. The recommended dosage of azacitidine is 75 mg/m(2) daily for 7 day...

The development of immunological abnormalities in various neoplasms is a rather common phenomenon. The prevalence of life-threatening systemic vasculitis in malignancy, however, is much lower. Nonetheless we found an unexpected frequency of several autoimmune manifestations, including systemic vasculitis, in certain myelodysplastic syndromes. We illustrate this finding with the case of a 43-yea...

Azacitidine is a pyrimidine nucleoside analogue with multiple mechanisms involved in its antineoplastic action. There is evidence that RNA metabolism is the primary target of this antimetabolite, although its inhibition of DNA methylation has been proposed as the main effect responsible for its clinical efficacy in myelodysplastic syndromes. In patients with myelodysplastic syndromes (MDS), aza...

Myelodysplastic syndromes (MDS) are heterogeneous clonal hematologic malignancies characterized by cytopenias caused by ineffective hematopoiesis and propensity to progress to acute myeloid leukemia. Innate immunity provides immediate protection against pathogens by coordinating activation of signaling pathways in immune cells. Given the prominent role of the innate immune pathway in regulating...

Myelodysplastic syndromes are characterized by a high risk of evolution into acute myeloid leukaemia which can involve activation of signalling pathways. As the chaperone heat shock protein 90 (HSP90) has a key role in signal transduction, we investigated its role in the pathogenesis and evolution of myelodysplastic syndromes. Expressions of HSP90 and signalling proteins clients (phosphorylated...

Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a ho...