%0 Journal Article
%T Clinical Experience Using Vitamin D and Analogs in the Treatment of Myelodysplasia and Acute Myeloid Leukemia: A Review of the Literature
%A Jonathan S. Harrison
%A Alexander Bershadskiy
%J Leukemia Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/125814
%X Despite progress in understanding the biology of acute myeloid leukemia (AML), and despite advances in treatment, the majority of patients with AML die from the disease. The observation that Vitamin D can induce AML blast cells in vitro to differentiate along the monocytic lineage was made 30 years ago; however, it remains to translate this into a clinically meaningful strategy. This is a review of published clinical experience regarding the use of Vitamin D and its analogs, either alone or in combination with other agents, to treat AML. In many of these reports, investigators included patients with myelodysplasia (MDS) as well as AML patients in their treatment cohorts; therefore reports of Vitamin D and its analogs in treating MDS are included. This review documents heterogeneity in selection criteria for patients treated in these studies, the spectrum of Vitamin D analogs used in various studies, and the differing dosing strategies employed by investigators. Despite examples of occasional clinical efficacy, barriers remain to the successful application of Vitamin D in the treatment of MDS and AML. These include the lack of definition of a particularly sensitive target population, and the as yet unknown optimal choice of Vitamin D analog and dosing schedule. 1. Introduction Despite significant progress over the past several decades in understanding the biology of acute myeloid leukemia (AML) and despite important advances in treatment approaches, the majority of patients who develop acute myeloid leukemia will still die from their disease. A recent analysis by Southwest Oncology Group investigators of data from 1344 patients with newly diagnosed AML enrolled into SWOG studies between 1986 and 2009, excluding Acute Promyelocytic Leukemia, illustrated this point dramatically. In that study, overall survival at 4 years was only 49% for patients with favorable cytogenetics; overall survival was approximately 25% for those with intermediate-prognosis cytogenetics, and only 9% for those with unfavorable cytogenetics [1]. Among the most important advances made in recent decades in the treatment of AML was the recognition of the exquisite sensitivity of Acute Promyelocytic Leukemia (APL) to differentiation therapy using all-trans-retinoic acid (ATRA). This observation was, shortly thereafter, accompanied by the identification of the Retinoic Acid Receptor Alpha (RARA) gene as a partner in the balanced translocation that drives APL. The dual recognition of a novel mechanism of disease¡ªin the case of APL, overexpression of RARA, a protein that participates in
%U http://www.hindawi.com/journals/lrt/2012/125814/