Developmental therapeutics for myelodysplastic syndromes.

The management strategy for patients with myelodysplastic syndromes (MDS) has evolved from sole reliance on supportive measures to active treatment guided by disease risks. Recent progress in understanding the molecular pathogenesis of MDS has accelerated the discovery of new therapeutic targets, and consequently launched the development of several novel therapeutics that are currently in varied stages of clinical testing. One such agent is lenalidomide, which has shown remarkable effectiveness in the cytogenetically defined subset of MDS with the chromosome 5q31 deletion. The advent of new and effective targeted therapeutics may beneficially affect outcomes of an ever-increasing number of patients with MDS. This discussion summarizes the preliminary results of selected novel therapeutics.

[1]  P. Greenberg,et al.  Hematologic and cytogenetic (CTG) response to lenalidomide (CC-5013) in patients with transfusion-dependent (TD) myelodysplastic syndrome (MDS) and chromosome 5q31.1 deletion: Results of the multicenter MDS-003 Study , 2005 .

[2]  J. Perentesis,et al.  Hyperleukocytosis complicating lonafarnib treatment in patients with chronic myelomonocytic leukemia , 2005, Leukemia.

[3]  Z. Estrov,et al.  Hematologic Improvement Following Treatment with TLK199 (Telintra™), a Novel Glutathione Analog Inhibitor of GST P1-1, in Myelodysplastic Syndrome (MDS): Interim Results of a Dose-Ranging Phase 2a Study. , 2004 .

[4]  A. Drosos,et al.  SCIO-469 Scios Inc. , 2004, Current opinion in investigational drugs.

[5]  E. Estey,et al.  Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  R. Kurzrock,et al.  Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the phase 1 setting. , 2003, Blood.

[7]  A. Barrett,et al.  A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. , 2003, Blood.

[8]  N. Harris,et al.  The World Health Organization (WHO) classification of the myeloid neoplasms. , 2002, Blood.

[9]  N. Young,et al.  Antithymocyte Globulin for Treatment of the Bone Marrow Failure Associated with Myelodysplastic Syndromes , 2002, Annals of Internal Medicine.

[10]  S. Amadori,et al.  Infliximab chimaeric anti‐tumour necrosis factor alpha monoclonal antibody treatment for patients with myelodysplastic syndromes , 2002, British journal of haematology.

[11]  P. Venugopal,et al.  Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. , 2001, Blood.

[12]  T. Grogan,et al.  Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. , 2001, Blood.

[13]  B. Cheson,et al.  Report of an international working group to standardize response criteria for myelodysplastic syndromes. , 2000, Blood.

[14]  M. Morgan,et al.  Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? , 2000, Blood.

[15]  P. Venugopal,et al.  Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone. , 2000, Blood.

[16]  J. Čermák,et al.  Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow , 1998, British journal of haematology.

[17]  N. Young,et al.  Antithymocyte globulin for patients with myelodysplastic syndrome , 1997, British journal of haematology.

[18]  T Hamblin,et al.  International scoring system for evaluating prognosis in myelodysplastic syndromes. , 1997, Blood.

[19]  H. Deeg,et al.  Fas (CD95) receptor and Fas-ligand expression in bone marrow cells from patients with myelodysplastic syndrome. , 1996, Blood.

[20]  Todd R. Golub,et al.  Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation , 1994, Cell.

[21]  M. Gordon.  Efficacy of Lenalidomide in Myelodysplastic Syndromes , 2006 .

[22]  Duardo,et al.  RESPONSE TO IMATINIB MESYLATE IN PATIENTS WITH CHRONIC MYELOPROLIFERATIVE DISEASES WITH REARRANGEMENTS OF THE PLATELET-DERIVED GROWTH FACTOR RECEPTOR BETA , 2002 .

[23]  P. Musto,et al.  Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndromes. , 2002, Haematologica.