Myelodysplastic syndrome medical therapy

Medical therapy
The goals of therapy are to control symptoms, improve quality of life, improve overall survival, and decrease progression to acute myelogenous leukemia.

The IPSS scoring system can help triage patients for more aggressive treatment (i.e. bone marrow transplant) as well as help determine the best timing of this therapy. Supportive care with blood product support and hematopoeitic growth factors (e.g. erythropoietin) is the mainstay of therapy. The regulatory environment for the use of erythropoietins is evolving, according to a recent US Medicare National Coverage Determination. No comment on the use of hematopoeitic growth factors for MDS was made in that document.

The IPSS uses 3 criteria; cytogenetic abnormalities, proportion of bone marrow myeloblasts and number of cytopenias. Points are assigned to these variables and are added to create 4 risk groups; low, intermediate 1, intermediate 2 and high risk. If patients have >10% blasts in their bone marrow by morphology they are automatically classified as having higher risk MDS. Patients with chromosome 7 abnormalities, loss of chromosome 7 or complex cytogenetics typically have high-risk MDS. A major limitation of the IPSS is that it does not distinguish between patients with severe and modest degrees of cytopenias; this may influence outcome.

Survival and AML evolution score

Intermediate = other abnormalities. Poor = complex (>/= 3 abnormalities) or chromosome 7 abnormalities.
 * Good = normal or any 1 of the following; deletion Y, deletion 5q, deletion 20q.
 * Hemoglobin < 10 g/dl, ANC<1800 /uL, Platelets <100,000.

Lower risk disease includes those classified as low or intermediate 1 with a combined IPSS score of 1 or lower. For these patients observation and supportive care only has been advocated. (However, once blood transfusions are required then some form of treatment should be considered.)

Since 2004 3 medications have been approved for MDS; 5-azacytidine and decitabine are hypomethylating agents, lenalidomide is immunomodulatory. Lenalidomide is especially useful in the treatment of 5q minus syndrome; for these patients the medication not only improves counts but it also has a high complete response rate in the bone marrow and a high remission rate for the chromosome. For non-5q deletion, low-risk MDS patients treatment options include lenalidomide and demethylating agents.

DNA-methyltransferase inhibitors; normally methylation of cytosine in gene promoters causes them to become silent; they would otherwise cause terminal differentiation. There is survival benefit with the hypomethylating agents (Decitabine & Azacitadine)in higher-risk disease (intermediate-2 or high risk disease).Azacitidine and Decitabine are different chemically and patients whose disease doesn't respond or becomes refractory to one may respond to the other. The recommendation is to proceed until progression; sometimes stopping allows the disease to relapse or it relapses as it is resistant disease. The major toxicities are nausea, vomiting, diarrhea, cytopenias and fatigue.

IMiDS, such as Lenalidomide are for erythroid failure such as in transfusion-dependent del(5q). The response rate (~67%)is independent of the karyoptype. Treatment can give a positive cytopgenetic response, the patient becomes transfusion-free and would no longer require Erythropoietin. With treatment there is a transient decrease in the leukocytes and platelets. It has been known to be useful in paients without the 5q deletion with ~25% of patients experiencing a significant response in hemoglobin levels. .