Improved Survival in Patients with Myelodysplastic Syndrome Receiving Iron Chelation Therapy

Leitch, Heather A.; Leger, Chantal S.; Goodman, Trisha A.; Wong, Karen K.; Wong, Danielle; Ramadan, Khaled M. A.; Rollins, M. D.; Barnett, Michael J.; Galbraith, Paul F.; Vickars, Linda M.

doi:10.3816/clk.2008.n.026

Cited by 81 publications

(69 citation statements)

References 42 publications

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“…The fact that, until recently, iron chelation treatment recommendations in MDS were based on limited data further complicates the picture (evidence grade B, level III) [18]. Nowadays, several comparative studies have shown that mortality is higher in heavily iron-overloaded patients [19,20] and that chelation treatment seems to improve survival in MDS patients [16,21]. The guidelines published to date regarding IO treatment agree that iron chelation therapy is indicated in patients with a ferritin level of 1,000 μg/L or more and/or who have received a transfusion of two units per month of PRBC for at least 1 year [16,21].…”

Section: Discussionmentioning

confidence: 99%

Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

et al. 2009

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. Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements. Annals of Hematology, Springer Verlag, 2009, 89 (2) Abstract The main objective of the study was to analyze the incidence of iron overload (IO) and its management in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) before the license of deferasirox. This observational, cross-sectional, and multicenter study was conducted from January to May 2007 in 81 Spanish hospitals. Eligible patients had a low or intermediate-1 risk score and had to have received at least ten units of packed red blood cell (PRBC). Of the 549 patients analyzed, 75% had received more than 20 PRBC units since diagnosis; 14% had IO at diagnosis and 58% at last follow-up. Thirty-eight percent of patients received chelation therapy; of those, 92% were treated with desferrioxamine. Ferritin levels at the start of chelation therapy were higher than 1,000 μg/L in 76% and over 2,500 μg/L in 24% of patients. Of the 202 patients who received some form of chelation therapy, ferritin levels increased from a mean±SD of 1,986±1,398 to 2,480± 1,648 μg/L at last follow-up in 86% (p<0.001). In the remaining 29 patients treated with a minimally effective therapy, ferritin levels did not increase. Of these, only 11 patients received such therapy lasting more than 12 months. In conclusion, most low-risk transfusion-dependent MDS patients develop IO, but only a minority receives a minimally effective and timely iron chelation therapy.

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Section: Discussionmentioning

confidence: 99%

Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

et al. 2009

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“…In that study, a Cox regression analysis indicated that median OS was correlated significantly with IPSS score (P < .008) and treatment with iron chelation therapy (P < .02). 50 For patients with low or Int-1 risk IPSS scores who received chelation therapy (n 5 18), the median OS was not reached at 160 months compared with a median OS of 40.1 months for nonchelated patients (n 5 160). Takatoku et al, in a retrospective analysis of 292 Japanese patients primarily with MDS (n 5 152) or aplastic anemia (n 5 90), also demonstrated that morbidity and mortality were influenced strongly by the occurrence of iron overload.…”

Section: Managing Body Iron Levelsmentioning

confidence: 97%

Red blood cell transfusions and iron overload in the treatment of patients with myelodysplastic syndromes

Jabbour

Kantarjian

Koller

et al. 2008

Cancer

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BACKGROUNDApproximately 15,000 new cases of myelodysplastic syndromes (MDS) are expected in the United States each year.METHODSThe mainstay for the management of myelodysplastic syndromes (MDS) is supportive therapy with red blood cell (RBC) transfusions to improve the patient's quality of life. RBC transfusions enable adequate tissue oxygenation and increase hemoglobin levels, improve fatigue, and improve the physical and intellectual activity of patients. Up to 90% of patients with MDS will receive RBC transfusions during the course of their disease, and many will become chronically dependent on transfusions to manage their anemia. These transfusions lead to an accumulation of excess iron that, in turn, can develop into a condition known as iron overload, causing clinical consequences like hypertransaminasemia and cirrhosis, dilated cardiomyopathy, and progressive dysfunction of the endocrine glands.RESULTSStudies in patients with MDS have indicated that iron overload because of RBC transfusions was an independent, adverse prognostic factor for overall survival (OS) and leukemia‐free survival (LFS): OS and LFS were significantly shorter in transfusion‐dependent patients with MDS than in those who were not transfusion dependent.CONCLUSIONSAlthough the National Comprehensive Cancer Network guidelines for the treatment of patients with MDS recommend the use of RBC transfusions as supportive care, they further recommend that the iron burden of transfused patients be monitored regularly and that iron chelation therapy be considered to maintain serum ferritin levels of <1000 ng/mL. Cancer 2008. © 2008 American Cancer Society.

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“…List et al [27] Low/lnt-1 15% (n = 173) 15% (n = 52) 22% (n = 77) Gattermann et al [28] Low/lnt-1 21.5% (n = 247) 22% (r = 50) 13% (n = 100) Nolte et al [29] Low/lnt-1 11% (n = 50) NR NR Angelucci et al [30] Low/lnt-1 Transfusion independence in 15.5% (n = 152) Table 2 Clinical studies showing that iron chelation improves survival in patients with lower risk MDS [32][33][34][35][36][37][38][39][40].…”

Section: Is There a Survival Benefit From Chelation Therapy (Ict)?mentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

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Improved Survival in Patients with Myelodysplastic Syndrome Receiving Iron Chelation Therapy

Cited by 81 publications

References 42 publications

Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

Red blood cell transfusions and iron overload in the treatment of patients with myelodysplastic syndromes

Iron overload in myelodysplastic syndromes (MDS)

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