Update on the therapy for myelodysplastic syndrome

Abstract

The myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic stem cell disorders characterized by cytopenias. Patients have a risk of developing acute leukemia though most subcome to complications of low blood counts. Over the past decade many novel treatments have been developed and investigation of new agents is ongoing. In this article, we discuss the classification and prognostic systems that are used in MDS, the agents available for treatment of MDS as well as review supportive and palliative care options for patients who are not candidates for, or opt against, newer treatment strategies. Am. J. Hematol. 84:177-186, 2009. V

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

“…Chelation may significantly reduce total body iron load and decrease the production of hydroxyl and oxygen radicals, thus lessening cellular and target organ damage and eventually enhancing survival in transfusion-dependent MDS patients [1,2,21,22]. Note, however, that the evidence for the use of chelation therapy in patients with MDS is based, not on randomized controlled trials, but on observational studies; including two recent ones which continue to provide evidence of an beneficial association between chelation therapy and iron status [32,33].…”

“…Further, it has been argued that advanced age or severe comorbidities should not preclude iron chelation therapy 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 [1], though careful evaluation of patients' frailty and consideration of life expectancy are recommended [2]. Other relevant decision factors include patients with elevated serum ferritin levels at the time of MDS diagnosis, in particular those with acquired sideroblastic anemia because of the risk of hematochromatosis [5], and patients on more liberal transfusion strategies where the target hemoglobin is higher than the 8-10g/dL typically maintained in MDS patients [1]. In fact, individually tailoring deferasirox dose to achieve therapeutic targets, with initial dosing based on transfusion requirements and titration per follow-up monitoring data, is recommended [32].…”

“…Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders characterized by cytopenias due to ineffective production of normal mature blood cells, with course of disease and prognosis dependent on subtype [1,2,3,4,5,6,7,8,9]. Up to 30% of patients progress to acute myelogenous leukemia (AML); while up to 65% of nonprogressing MDS patients will develop progressive cytopenia(s) [5].…”

“…From 80% to well over 90% of MDS patients develop anemia, with over half presenting with hemoglobin levels below 10 g/dL [12,13,14]. Almost all MDS patients are likely to require red blood cell (RBC) transfusions at some point, and for 40% of patients this will be the sole therapeutic option to manage their anemia, prevent anemia-related comorbidity and decline in physical performance, and enhance quality of life [1]. Despite these potential benefits, transfusion-dependence in MDS patients is associated with increased risk of disease progression [4,13,15,16] and shorter survival [4,13,15,17].…”

“…The circulating non-transferrin-bound iron produces hydroxyl and oxygen radicals that cause lipid peroxidation and damage to cell membranes, protein, and DNA [2,21], especially in target organs such as heart, liver, and endocrine glands [1,22]. Iron overload is associated with reduced survival: adjusting for transfusion burden, hazard rates increase by 30% for every 500 g/L increase in serum ferritin above the threshold of 1000 μg/L [4].…”