Elsevier

Seminars in Oncology

Volume 38, Issue 5, October 2011, Pages 673-681
Seminars in Oncology

Myelodysplastic syndrome
Treatment of Higher-Risk Myelodysplastic Syndrome

https://doi.org/10.1053/j.seminoncol.2011.07.001Get rights and content

The myelodysplastic syndromes (MDS) are divided into lower-risk and higher-risk categories. This differentiation is important for treatment selection. Over the last decade, we have witnessed significant improvements in the treatment of patients with higher-risk MDS that have resulted in improved survival with the hypomethylating agent 5-azacytidine This has resulted in a shift from the use of acute myelogenous leukemia (AML)-like therapies, which were traditionally offered to this group of patients in the past, to the hypomethylating agents, which have become the standard of care. Despite these advances, new therapies or combinations are needed to improve response and survival rates. This review will summarize results from current available therapies and discuss potential needs and ongoing research in the area of treatment of higher-risk MDS.

Section snippets

Targeting DNA Methylation: 5-Azacytidine and Decitabine

DNA methylation is the addition of a methyl group to a cytosine when followed by a guanine, the so-called CpG pair.6 CpG pairs can cluster in gene promoter areas where methylated gene expression can be repressed. This is a reversible process in that removal of methylation, for example with a hypomethylating agent, results in gene reactivation. Cancer, and leukemias in particular, are characterized by methylation of multiple gene promoters.7 Indeed, a subset of patients with MDS is characterized

Does Intensive Chemotherapy have a Role in Higher Risk MDS?

Intensive chemotherapy protocols in higher-risk MDS have generally used classical anthracycline/ara-C combinations modeled after those used in AML.32, 33 No drug in combination with ara-C has so far proved superior to anthracycline/ara-C combinations.34 When used in MDS, intensive chemotherapy results in lower CR rates (40%–60%) and shorter CR duration (median duration of 10–12 months), and tends to be associated with more prolonged periods of aplasia. The feasibility of intensive chemotherapy

The Role of Allogeneic Stem Cell Transplantation in Higher Risk MDS

AlloSCT is the only curative treatment for higher-risk MDS. Results from selected studies report prolonged disease-free survival in about 30% to 50% of patients.35 However, its use is mainly restricted to younger patients with an appropriate donor. The most important question for the practicing physician is the timing of transplant. A study from the International Bone Marrow Transplant Registry (IBMTR) indicated that early transplantation in higher-risk MDS was associated with longer life

Investigational Options for Patients With Higher-Risk MDS

Despite the results with the hypomethylating agents, it is obvious that we need better and newer therapies for higher-risk MDS. Although there is an impact on survival as discussed above, response rates are low and most patients will eventually lose response. At present there are three approaches to improve outcomes in MDS. First is the development of new hypomethylating agents; second is the development of combinations with the hypomethylating agents; and third is the incorporation of new

A Practical Approach to the Patient With Higher-Risk MDS

Treatment decisions in higher-risk MDS need to consider the following three characteristics: age, potential for alloSCT, and cytogenetics. In an older individual who is not a candidate for alloSCT, the best approach based on current data from randomized clinical trials is to use a hypomethylating agent for as long as possible, probably until disease progression. The same applies to the younger patient who is not a candidate for transplant. The decision is more complex in patients who are

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