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Immunomodulatory Drugs: New Options for the Treatment of Myelodysplastic Syndromes.
MedLine Citation:
PMID:  23153925     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Myelodysplastic syndromes (MDS) are common adult hematologic disorders characterized by ineffective hematopoiesis with progressive cytopenia and a risk of evolving into currently incurable acute myeloid leukemia. Until recently, the only treatment was bone marrow transplantation, but, over the past few years, a new therapeutic approach based on immunomodulatory drugs (IMiD) has been developed. IMiDs belong to a therapeutic class whose progenitor is thalidomide, a synthetic derivative of glutamate that was initially used because of its sedative and antiemetic properties but was then withdrawn because of its teratogenic effects. IMiDs represent a major advance in the treatment of multiple myeloma at different disease stages, 5q minus syndrome, acute myeloid leukemia with the 5q deletion, mantle cell lymphoma, relapsing or unresponsive high-grade lymphoma, and relapsing indolent lymphoma. METHODS: Medical databases and conference proceedings were searched to identify articles and clinical trials that have investigated or are investigating the use of IMiDs on MDS. RESULTS AND DISCUSSION: An important part of their in vivo efficacy is attributed to their immunomodulatory properties because they potentiate the immune response by restoring dendritic cell function and inhibiting T-cell regulatory activity, which leads to the activation of T lymphocytes and natural killer T cells by increasing the production of interleukin-2 and interferon gamma. IMiDs are characterized by antitumoral and antiangiogenic activities, and they also induce the apoptosis of neoplastic cells. Thalidomide and its derivative lenalidomide have been proposed for the treatment of MDS because of their action on the immune mechanisms that appear to play an important role in the pathophysiology of this syndrome. CONCLUSIONS: This article examines the pharmacology and molecular action of IMiDs and the evidence of their efficacy in treating patients with MDS in different risk classes.
Authors:
Roberto Castelli; Ramona Cassin; Antonino Cannavò; Massimo Cugno
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-12
Journal Detail:
Title:  Clinical lymphoma, myeloma & leukemia     Volume:  -     ISSN:  2152-2669     ISO Abbreviation:  Clin Lymphoma Myeloma Leuk     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101525386     Medline TA:  Clin Lymphoma Myeloma Leuk     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Pathophysiology and Transplantation, Section of Internal Medicine, University of Milan, Milan, Italy, and Department of Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda Policlinico, Milan, Italy. Electronic address: roberto.castelli@unimi.it.
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