TAILIEUCHUNG - Chapter 102. Aplastic Anemia, Myelodysplasia, and Related Bone Marrow Failure Syndromes (Part 15)

Myelodysplasia: Treatment The therapy of MDS has been unsatisfactory. Only stem cell transplantation offers cure: survival rates of 50% at 3 years have been reported, but older patients are particularly prone to develop treatment-related mortality and morbidity. Results of transplant using matched unrelated donors are comparable, although most series contain younger and more highly selected cases. MDS has been regarded as particularly refractory to cytotoxic chemotherapy regimens but is probably no more resistant to effective treatment than acute myeloid leukemia in the elderly, in whom drug toxicity is often fatal and remissions, if achieved, are brief. Low doses of cytotoxic drugs. | Chapter 102. Aplastic Anemia Myelodysplasia and Related Bone Marrow Failure Syndromes Part 15 Myelodysplasia Treatment The therapy of MDS has been unsatisfactory. Only stem cell transplantation offers cure survival rates of 50 at 3 years have been reported but older patients are particularly prone to develop treatment-related mortality and morbidity. Results of transplant using matched unrelated donors are comparable although most series contain younger and more highly selected cases. MDS has been regarded as particularly refractory to cytotoxic chemotherapy regimens but is probably no more resistant to effective treatment than acute myeloid leukemia in the elderly in whom drug toxicity is often fatal and remissions if achieved are brief. Low doses of cytotoxic drugs have been administered for their differentiating potential and from this experience has emerged drug therapies based on pyrimidine analogues. Azacitidine is directly cytotoxic but also inhibits DNA methylation thereby altering gene expression. Azacitidine improves blood counts and modestly improves survival in about 16 of MDS patients compared to best supportive care. Azacitidine is administered subcutaneously at a dose of 75 mg m2 daily for 7 days at 4-week intervals for at least four cycles although further cycles may be required to observe a response. Decitabine is closely related to azacitidine and more potent. Similar to azacitidine about 20 of patients show responses in blood counts with a duration of response of almost a year. Activity may be higher in more advanced MDS subtypes. Decitabine dose is 15 mg m2 by continuous intravenous infusion every eight hours for three days repeating the cycle every 6 weeks for at least four cycles. The major toxicity of both azacitidine and decitabine is myelosuppression leading to worsened blood counts. Other symptoms associated with cancer chemotherapy frequently occur. Ironically it has been difficult to establish that either agent acts in patients by a .

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• Myelodysplasia
• Related Bone Marrow Failure Syndromes
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• Severe aplastic anemia
• Hematopoietic stem cell transplantation
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