Low intensity therapy

Erythropoietin ± G-CSF treatment of symptomatic anaemia in MDS:

maintenance of stable augmented Hb may provide better quality of life than the cyclical fluctuations of transfusion programmes; responses in 20-30% to Epo alone, 40-60% to Epo+G-CSF; synergistic effect most evident in RARS or patients with serum Epo levels <500U/L; check iron stores and replete if necessary.

• For patients with RA/RAEB with symptomatic anaemia, transfusion requirement <2 units/month and a basal Epo level of <200U/L consider trial of Epo (10,000 units daily for 6 weeks); in non-responders consider adding daily G-CSF (Img/kg/day) SC or double dose Epo or both for further 6 weeks; no response after 2-3 months = treatment failure; in responders, reduce G-CSF to 3 x weekly and Epo in steps to lowest dose retaining response.

• For patients with RARS with symptomatic anaemia, transfusion requirement < 2 units/month and basal Epo levels <500 U/L combined therapy should be used from outset; consider Epo dose escalation if no response after 6 weeks; no response after 2-3 months = treatment failure; in responders titrate doses and frequency as tolerated.

G-CSF treatment of neutropenia: for patients with neutropenia and recurrent or antibiotic resistant infections but not recommended for chronic prophylaxis.

Immunosuppression: may be effective notably for patients with hypoplastic MDS but also for other patients with low risk MDS (IPSS< intermediate-1).

• ATG in clinical trials at a dose of 40mg/kg/d x 4d achieved transfusion independence in ~33% patients (median response >2 years); sustained neutrophil and platelet responses in up to 50%; response associated 231 with significant survival benefit.

• Cyclosporin A has achieved transfusion independence in a high proportion of patients with RA in small clinical trials; improved neutrophil and platelet counts also.

• Younger age, shorter duration of transfusion dependence, HLA-DRB1* 15, hypoplastic BM and presence of a PNH clone associated with response to immunosuppression.

Non-intensive chemotherapy: may be tolerated by elderly patients with transformed or 'transforming' MDS; but transient reductions in blast counts may be at the price of increased cytopenia and transfusion dependence.

• Hydroxyurea is used to control monocytosis in CMML; titrate dose to achieve optimum control of myeloproliferation with minimum additional cytopenia; it is preferable to oral etoposide.

• Low dose melphalan (2mg/d) is under examination after small trials show a response rate of 40% in patients with RAEB or RAEB-t without severe side effects and prolonged survival in responders; best responses in hypoplastic MDS.

• 5-azacytidine: shows promise with 60% responses, decreased risk of AML transformation, improved QoL and improved survival in phase III trials.

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