Journal
CURRENT OPINION IN HEMATOLOGY
Volume 14, Issue 2, Pages 123-129Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0b013e328016847a
Keywords
deletion 5q; lenalidomide; myelodysplatic syndrome
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Purpose of review The aim of this article is to discuss the relevant pathobiologic effects of lenalidomide and the most recent clinical evidence to support its use in patients with myelodysplastic syndrome. Recent findings Lenalidomide is an immunomodulatory agent with biological activity in several hematologic malignancies, including myelodysplastic syndrome. The precise mechanism yielding benefit in patients with myelodysplastic syndrome and 5q(-) syndrome is not clear, but various molecular and pathogenic targets have been identified. Enhancement of cellular immunity through T-cell and NK-cell activation and suppression of inflammatory cytokines and pro-angiogenic peptides upon lenalidomide treatment has been demonstrated in in-vitro models of myelodysplastic syndrome. Furthermore, lenalidomide induces a direct cytotoxic effect against 5q(-) clones in leukemia cell lines and enhances ligand-induced erythropoietin receptor signaling in erythroid progenitors. Clinical trials with lenalidomide in myelodysplastic syndrome have supported the in-vitro evidence of karyotype-dependent activity by demonstration of a high frequency of cytogenetic and pathologic responses in patients with myelodysplastic syndrome and deletion of chromosome 5q. Lenalidomide was approved for the treatment of transfusion-dependent patients with low to intermediate risk myelodysplastic syndrome and chromosome 5q deletion. Summary Lenalidomide is an active immunomodulatory agent for the treatment of myelodysplastic syndrome with encouraging erythropoetic and cytogenetic remitting activity that is karyotype dependent.
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