Alan F List

..The identification of relevant biologic targets in MDS has raised expectations for the development of disease-specific therapies for MDS in the years that follow...

..This study measured how myelodysplastic syndrome (MDS) patients value transfusion independence (TI), reduced transfusions (RT) and transfusion-dependence (TD) using health utility assessment methodology...

..In patients with myelodysplastic syndromes and symptomatic anemia, we evaluated the safety and hematologic activity of lenalidomide, a novel analogue of thalidomide...

..Multicenter phase II and III studies are under way to further assess the erythroid and cytogenetic response rates in distinct subtypes of MDS, including 5q- deletion, and to optimize its clinical application...

..Further trials are ongoing for many other malignancies. This report will review the preclinical and clinical results of the investigations with this exciting new therapeutic, its toxicities and future prospects...

..To evaluate receptor-selective trophic response to VEGF-A in AML cells, we investigated receptor-specific ligand activation responsible for VEGF-initiated clonogenic response...

..Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc...

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..The benefits of lenalidomide plus rhu-EPO are currently under investigation in a phase 3 Eastern Cooperative Oncology Group (ECOG)-sponsored intergroup study. This study is registered at www.clinicaltrials.gov as NCT00910858...

..This article reviews the clinical experience with lenalidomide, highlighting recent understanding of the dual karyotype-dependent mechanisms of action...

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..The authors evaluated predictive factors in patients with secondary AML treated with anthracycline-based induction therapy...

..The most common adverse reactions include dose-dependent neutropenia and thrombocytopenia that are more pronounced in patients with del(5q) in whom early suppression of the clone is expected...

..Finally, we highlight the current understanding of its mechanism of action, discussing the emerging insight into the underlying biology of del(5q) MDS and its linkage to potential targets of lenalidomide...

..Based on these findings, Treg(EM) cell expansion may be synonymous with human Treg activation and indicate microenvironmental changes conducive to transformation in myelodysplastic syndromes...

..We highlight the mechanism of action and the recent advances in understanding the biology of del (5q) MDS. We also explore its potential use and the efforts to further improve its activity in non-del (5q) MDS...

..We discuss herein the current understanding of the biology of the 5q- syndrome, actions of efficacy of lenalidomide and strategies for clinical management...

..2% for MEC (P=0.09), with median OS of 11 and 4.5 months, respectively (P=0.07). In first relapse, CR was 36.8% and 25.9% (P=0.35) and median OS was 6.7 and 6.7 months, respectively (P=0.87). Our data support use of CLAG for RR-AML...

..This discussion examines the current NCCN guidelines for the treatment of these patients, including the management of anemia in lower-risk MDS, and discusses the potential future therapeutic applications of lenalidomide in this disease...

..We use a case-based format to discuss current options for treatment, including erythropoiesis-stimulating agents, hypomethylating agents, lenalidomide, immunosuppressive therapy, supportive care, and investigational agents...

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..We applied the MDAS to Moffitt Cancer Center (MCC) MDS patients to validate its prognostic utility...

..The evolution of the use of thalidomide as a therapeutic for diseases such as multiple myeloma and myelodysplastic syndrome and the promising initial results of the new IMiDs will be reviewed...

..8 months. Overall survival from diagnosis to the last follow-up in patients with LC was 28.2 months, shorter than patients without LC (44 months). LC and its equivalent could predict disease progression to AML...

..While most non-registered MDS patients showed resource utilization and survival characteristics consistent with lower-risk MDS, a subset was registered as acute myeloid leukemia (7.6%) and accounted for early mortality...

..With the emerging data elucidating the pathogenesis of the 5q- syndrome and the success of clinical trials, a cohesive story connecting the biology and pharmacology associated with this subtype of myelodysplastic syndromes has emerged...

..The National Comprehensive Cancer Network Clinical Practice Guidelines recently added lenalidomide to the therapeutic algorithm for MDS as front-line therapy for lower-risk MDS patients with del(5q) and transfusion-dependent anemia...

..We investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal 5q31- clone in patients with this disorder...

..This review will explore the pharmacokinetic and biologic effects of thalidomide and its progeny compounds...

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..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...

..As we continue to collect clinical experience with these agents, the repertoire of available therapeutics for the treatment of MDS will expand and provide a foundation for novel therapeutic combinations...

..This 3-year, prospective, multicenter trial assessed the safety and efficacy of deferasirox in low- or intermediate-1-risk myelodysplastic syndrome (MDS)...

..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...

..A phase III Intergroup trial (ECOG 2905) will test the capacity to potentiate erythropoietin response by comparing response to lenalidomide monotherapy to the combination of darbepoetin and lenalidomide in non-deletion 5q MDS patients...

..MDS became reportable to the Surveillance, Epidemiology, and End Results Program (SEER) in 2001. We report first study of MDS among large population in the Veteran Affair system...

..These data establish a role for allelic haplodeficiency of the lenalidomide inhibitable Cdc25C and PP2Acalpha phosphatases in the selective drug sensitivity of del(5q) MDS...

..Combination strategies are now in both MDS and AML that could further broaden the therapeutic potential of lenalidomide...

..The aim of this article is to discuss the proposed mechanisms of action, clinical trial data, and clinical implications for use of the immunomodulatory drugs in the treatment of myelodysplastic syndrome...

..Taken together, our findings indicate that HG-829 is a potent, long-acting, and noncompetitive modulator of P-glycoprotein export function that may offer therapeutic promise for multidrug-resistant malignancies...

..Of the MPNs, MF presents with the most severe morbidity and greatest mortality. Although the cause of MF is unknown, it is thought to occur from acquired mutations that target the hematopoietic stem cell...

..Future studies are needed to further investigate constitutional telomere attrition as a possible predisposing factor for MDS...

..An immune-mediated mechanism is likely to contribute to MDS early after diagnosis. New approaches that interfere with inflammatory pathways in the bone marrow microenvironment may move closer toward sustained disease control in MDS...

..Our study is the first to demonstrate that JAK2-V617F signalling is dependent on lipid rafts and that statins may be effective in a potential therapeutic approach for MPNs...

..In this review, data accumulated in the US, Europe, and Asia will be summarized to provide insight and direction for a multi-center international trial...

..These results support day 90 hypoalbuminemia as an adverse prognostic marker for NRM and OS after allo-HCT for acute myelogenous leukemia and myelodysplastic syndrome...

..This review presents the data related to iron overload in MDS, including its prevalence, diagnosis, clinical impact, and management...

..These data indicate that Src-STAT5 and Src-Akt pathways are integral survival signal pathways in AML cells. Src inhibition may represent a novel treatment strategy for investigation in AML...

..MDS incidence rates significantly increased with calendar year in 2001 through 2004, and only 4% of patients were reported to registries by physicians' offices. Thus, MDS disease burden in the United States may be underestimated...

..The current active treatment paradigm for MDS incorporates the most recent strategies yielding improved disease outcomes and patient survival...

..The importance of new advances in myelodysplastic syndrome will be discussed in this review...

..In particular, hydroxamic acid-based polar compounds and cyclic tetrapeptides have shown activity against cancers at well-tolerated doses...

..Evasion of NK immunosurveillance may have importance for MDS disease progression...

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..AG-01736 had minimal biologic or clinical activity in this elderly patient population...

..To evaluate the efficacy and safety of arsenic trioxide monotherapy in patients with myelodysplastic syndromes (MDS)...

..Confirmation of these findings awaits results of an ongoing randomized phase III trial (MDS-004 study)...

..These data directly implicate TGF-beta signaling in the pathobiology of ineffective hematopoiesis and identify TBRI as a potential therapeutic target in low-risk MDS...

..Lenalidomide has clinically meaningful activity in transfusion-dependent patients with low- or int-1-risk MDS who lack the deletion 5q karyotypic abnormality...

..Here, no CEBPA mutation in 95 CML-BC patients was found, suggesting a limited role, if any, of CEBPA mutations in this disorder...

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..One (3%) and five (17%) patients achieved complete remission and clinical improvement, respectively. PTK/ZK has modest activity in patients with MMM...

..Lessons learned from investigations of these and other mechanisms of cellular defense hold promise for a renaissance in the development of targeted therapeutics in acute leukemia...

..However, federal funding for cancer prevention is less than half that of cancer treatment. As a result of its enormous potential for extending life, cancer prevention warrants increased funding and support from federal funding agencies...

..001). We show, for the first time, that SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions...