The IRON2 Study. A Retrospective Observational Study to Describe the Evolution of Iron Overload in Patients with Low-Risk Myelodysplastic Syndrome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1723-1723 ◽  
Author(s):  
Angel Remacha ◽  
Beatriz Arrizabalaga ◽  
Ana Villegas ◽  
Maria Soledad Duran ◽  
Lourdes Hermosin ◽  
...  
Keyword(s):  
Observational Study ◽  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Median Number ◽  
Low Risk ◽  
Cardiac Complications ◽  
Iron Chelation Therapy ◽  
Free Survival

Abstract Abstract 1723 Introduction and Objective: A large number of patients with low-risk myelodysplastic syndrome (MDS) need blood transfusions, being iron overload an inevitable consequence that may cause hepatic fibrosis and cirrhosis, diabetes or myocardiopathy unless it is not treated. The main objective of this study is to describe the evolution of iron overload in transfusion-dependent patients with low-risk MDS. Secondary objectives include the evaluation of the impact of iron chelation therapy on Event Free Survival (EFS) (including infections, arthropathy, diabetes mellitus, hepatic and cardiac complications), Overall Survival (OS) and Leukemia Free Survival (LFS). Methods and Patients: Retrospective observational study carried out in Haematology Departments of 47 Spanish hospitals between March 2010 and March 2011. Transfusion-dependent patients with low/intermediate-1 IPSS risk who had received ≥10 red blood cell (RBC) transfusion during at least 12 months previous to study entry were eligible. Results: A total of 263 patients were evaluated [age at diagnosis, 74 ± 10.5 years]. IPSS classification was available in 82.9% included patients (lack of cytogenetics in 37 patients), classified as low risk (86%) and int-1 risk (14%). At diagnosis, 25.5% of patients had serum ferritin (SF) levels >500ng/ml, 8.7% SF>1,000ng/ml, and 22% TSI>50%. The median number of RBC transfusions per month was 2.35 RBC/month; during the course of the disease, 82.4% of patients reached SF levels >1,000ng/ml. Cardiac complications worsened/appeared in 24.4% of patients, having received a median RBC transfusions of 22 (7–92), and showing a median SF levels of 1,365 (735–3,025) ng/ml. One-hundred forty-seven (55.9%) patients started iron chelation therapy (85.5% with deferasirox) with a median number of RBC transfused of 23 (14–38) and a median SF levels of 1,570 (1,231.5–2,195) ng/ml. 71% of patients with SF>1,000ng/ml were on iron chelation therapy. Table 1 shows the results of univariate analysis of EFS, OS and LFS. As part of this study, we are currently performing a multivariate analysis whose results will be presented in forthcoming congress. Conclusions: The results of this study show that a high percentage of transfusion-dependent patients with low-risk MDS (82.4%) reach SF levels >1,000ng/ml during the course of their disease. Patients on iron chelation therapy show a higher cardiac EFS, OS and LFS compared with those not treated, being deferasirox the most frequently used chelating agent in clinical practice. Disclosures: Sanz: Novartis Farmaceutica S.A.: Employment.

Evolution of iron overload in patients with low-risk myelodysplastic syndrome: iron chelation therapy and organ complications

2014 ◽  
Vol 94 (5) ◽  
pp. 779-787 ◽  
Author(s):  
Ángel F. Remacha ◽  
◽  
Beatriz Arrizabalaga ◽  
Ana Villegas ◽  
María Soledad Durán ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Low Risk ◽  
Iron Chelation Therapy ◽  
Organ Complications

Improved Survival in Patients with Myelodysplastic Syndrome (MDS) Receiving Iron Chelation Therapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 249-249 ◽  
Author(s):  
Heather A. Leitch ◽  
Trisha A. Goodman ◽  
Karen K. Wong ◽  
Linda M. Vickars ◽  
Paul F. Galbraith ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Iron Overload ◽  
Causes Of Death ◽  
Clinical Evidence ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Low Risk ◽  
Iron Chelation Therapy

Abstract Patients (pts) with MDS and iron overload often receive iron chelation therapy (ICT), although there are no data demonstrating that this improves clinical outcome. Pts with thalassemia receiving ICT do have improved survival and a decrease in number of end-organ toxicities. We performed a retrospective review of 178 pts seen at St.Paul’s Hospital in Vancouver, Canada, from January 1981 to April 2006, with a bone marrow diagnosis (Dx) of MDS. Clinical data were collected from the practice database, the Iron Chelation Program of British Columbia database, and by chart review. Pts receiving ICT were treated with desferroxamine 0.5–3g by subcutaneous infusion over 12 hours, 5 days per week. 105 were male and 73 female. MDS Dx were: RA, n=36; RARS, n=42; RAEB, n=28; RAEB-t or AML, n=16, CMMoL, n=25; other, n=31. Age at Dx was a median of 69 (18–94) years. Median absolute neutrophil count (ANC) was 1.6 (33–155) G/l, hemoglobin (Hgb) 96.5 (33–155) G/l, and platelet count 115 (7–644) G/l. Cytogenetic analysis was available in 128 pts; low risk (as defined by the IPSS), n=85; intermediate, n=22; high, n=21. Calculation of IPSS score was feasible in 133 pts; low risk, n=44; int-1, n=55; int-2, n=17; high, n=17. An elevated ferritin level, defined as a serum ferritin of ≥ 2000 ug/ml, was found in 28 pts. Clinical evidence of iron overload was present in 22 pts; CHF with no other contributing factor n=5; liver disease n=18; endocrine dysfunction, n=4; other, n=4; biopsy or imaging evidence was available in 6 pts. Of 18 pts receiving ICT, median duration of ICT was 15 (0–37) months (mo) and reasons for initiating ICT were: elevated ferritin, n=13; clinical and biochemical evidence of iron overload, n=3; number of transfusions received, n=2. In ICT pts, median ferritin level pre-ICT was 4215 (1500–8400) and post-ICT was 2659 (567–5228). In non-ICT pts with elevated ferritin, median ferritin after Dx was 1647 (265–5009) ug/L and at recent follow up was 3188 (763–12723) ug/L. There was a trend toward higher initial ferritin level in ICT pts (p<0.07) and significantly lower post-ICT ferritin in ICT pts compared to follow up ferritin in non-ICT pts (p<0.003). Documented causes of death in non-ICT pts were AML, n=22; MDS-related, n= 21; infection/sepsis, n=18 and non-MDS related, n=10. Documented causes of death in ICT pts were AML, n=1; MDS related, n=1; iron overload, n=1. Kaplan-Meier analysis showed that median overall survival (OS) for all pts was 36 (0.7–255.9) mo. Age showed a trend toward significance for OS (p<0.1); other factors that were significant included IPSS score, (p<0.0001); Dx, (p<0.0001); number of red blood cell units transfused, (p<0.0001); occurrence of ≥1 serious infectious episode, (p< 0.002); AML transformation, (p<0.0001); MDS-directed treatment, (p<0.04); elevated ferritin, (p<0.004); clinical evidence of iron overload, (p<0.001); and ICT, (p<0.001). In Cox regression analysis, the only factors significant for OS were IPSS score (p<0.008) and ICT (p<0.02). For pts with low or int-1 IPSS, median OS for pts receiving ICT was not reached at 160 mo vs. 40.1 (0.7–224) mo for non-ICT pts (p<0.03). In conclusion, although we were not able to demonstrate a decrease in organ dysfunction in pts receiving ICT for MDS, there was a significant improvement in OS. These are to our knowledge the first data documenting improvement in clinical outcome in pts with MDS receiving ICT.

Review Of Published Survival Evidence For Iron Chelation Therapy (ICT) In Patients With Myelodysplastic Syndromes (MDS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5221-5221
Author(s):  
Keith Tolley ◽  
Joao Vieira ◽  
Craig Foster ◽  
Amanda Strickson ◽  
Stephanie Kundishora
Keyword(s):  
Iron Overload ◽  
Lower Risk ◽  
Survival Benefit ◽  
Chart Review ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Low Risk ◽  
Iron Chelation Therapy ◽  
Published Evidence ◽  
Acute Myeloid

Abstract Iron overload due to frequent blood transfusions in patients with myelodysplastic syndrome (MDS) is associated with complications, including a risk of cardiac disease and transformation to acute myeloid leukaemia (AML). Iron chelation therapy (ICT) with deferasirox and desferrioxamine is an essential part of the management of iron overload in low and intermediate prognostic risk MDS patients [NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes; Bennett 2008]. However, despite the risks of cardiac complications and AML, prior to 2009 there was little published evidence that ICT could improve survival outcomes in patients with MDS. A PubMed and ASH abstract search (conducted July 2013) has revealed a growing body of evidence indicating increased survival of a median of 2 – 6 years in transfusion-dependent MDS patients treated with ICT, relative to patients without ICT (see Table).ReferenceStudy objectiveStudy designTreatments/patient numbersKey resultFox 2009Neukirchen 2012Survival outcomes in MDS pts receiving ICTRetrospective matched-pair analysis N=188 low-int. MDS:N=94 ICTN=94 no ICTMedian survival = 74 mths in ICT pts vs. 49 mths in non-ICT pts (p=0.002)Raptis 2009Outcomes in low-risk MDS pts with/ without ICTRetrospective, single-arm analysis: 9 US institutionsN=78 low risk MDS:N=32 ICTN=46 no ICTMedian Overall Survival (OS) = 103 mths in chelated = pts vs. 55 mths in non-chelated pts; p=0.02; multivariate HR 0.372, p=0.03Rose 2010Analyse survival in transfusion-dependent, low-risk MDS pts pts with/ without ICTMultivariate prospective analysis in low/Int-1 IPSS MDS: 18 centers in FranceN=97 low-int. MDSN=44 no ICTN=53 ICTMedian OS 53 mths in non-ICT pts, 124 mths in ICT pts (p=<0.0003). In multivariate analysis ICT significantly associated with improved OS (HR of 0.386, CI: 0.196-0.757, p=0.005). Leitch 2011Survival outcomes in MDS pts receiving DFORetrospective chart review of 178 MDS pts in CanadaN=178 low-int. MDS receiving DFOIn MDS pts receiving ICT, there was a significant improvement in OS. Median OS for all MDS pts = 36 mthsLyons 2011Impact of chelation on clinical outcomes and OS in low-risk MDS ptsRetrospective analysis from MDS registry: 107 US centresN=600 low-int. MDSN=263 received ICT, (191 received ≥6 mths)Mean time to AML transformation was 27.3 mths in non-ICT pts vs. 40.6 mths in ICT pts. Median survival 52.2 (with ICT) vs.99.3 mths (no ICT); p<0.0001Komrokji 2011 Impact of ICT on OS, AML transformation in low-risk MDS ptsRetrospective pt chart review from a US centre N=97 low-int. MDS:N=45 ICT (N=35 DFX; N=10 DFO)N=52 no ICTMedian OS 59 mths for pts with ICT vs. 33.7 mths no ICT (p<0.013; HR 0.52). Leitch 2012Survival outcomes in lower risk/RARS pts with ICTRetrospective pt chart review in CanadaN=268 lower risk MDSLower IPSS /Non-RARS diagnosis associated with improved survival. Median OS for non-RARS without ICT =44 mths and with ICT, OS was not reached (p<0.0001). No significant difference between RARS with ICT (134.4 mths) or without ICT treatment (99 mths).Pts: patients; ICT: iron chelating therapy; MDS: myelodysplastic syndrome; SC: Subcutaneous infusion; RA: Refractory anaemia; AML: acute myeloid leukaemia; OS: overall survival; IPSS: International Prognostic Scoring System; HR: hazard ratio; INT-1: intermediate-1; DFX: deferasirox; DFO: desferrioxamine; RARS: ring sideroblasts; SF: Serum ferritin; mths: months All the published evidence for survival benefit is in lower IPSS risk MDS patients, with a significant survival benefit seen in the sub-group of patients with non-RARS (Leitch 2012). The main limitation of the studies is that they are all based on retrospective or prospective observational study designs; hence have a risk of selection bias, although many utilize multivariate techniques to control for confounding factors. Furthermore, none of the studies assess survival associated with type of ICT although there is an ongoing RCT (TELESTO) addressing the impact of deferasirox on OS in low risk MDS patients. In addition, it would be useful to explore whether the observational data from each study could be pooled to assess OS outcomes in transfusion-dependent lower risk MDS, by MDS sub-group and by type of ICT. In conclusion, there is now extensive evidence of an association between ICT and survival improvement in transfusion-dependent lower prognostic risk MDS patients. Disclosures: Tolley: Tolley Health Economics: Consultancy. Off Label Use: ICT for patients with iron overload due to blood transfusion in patients with MDS. Vieira:Novartis: Employment. Strickson:Tolley Health Economics: Consultancy. Kundishora:Novartis: Employment.

scholarly journals Adherence to Iron Chelation Therapy and Its Determinants

2021 ◽  
Author(s):  
Sukhmani Sidhu ◽  
Shruti Kakkar ◽  
Priyanka Dewan ◽  
Namita Bansal ◽  
Praveen C. Sobti
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Liver Iron ◽  
Free Survival ◽  
Liver Iron Overload ◽  
The Impact ◽  
Study Questionnaire

Background: Thalassemia is a chronic disease requiring lifelong treatment. The adherence to regular iron chelation therapy is important to ensure complication-free survival and good quality of life. The study aim to assess the adherence to iron chelation therapy (ICT) in patients with transfusion-dependent thalassemia (TDT), evaluate various causes of non-adherence and study the impact of non-adherence on the prevalence of complications secondary to iron overload. Materials and Methods: Patients with TDT on ICT for > 6 months were enrolled in the study. Hospital records were reviewed for demographic details, iron overload status, treatment details, and the prevalence of complications. A study questionnaire was used to collect information on adherence to ICT, knowledge of patients, and the possible reasons for non-adherence. Results: A total of 215 patients with a mean age of 15.07+7.68 years and an M: F ratio of 2.2:1 were included in the study. Non-adherence to ICT was found in 10.7% of patients. Serum ferritin levels were significantly higher in the non-adherent group (3129.8+1573.2 µg/l) than the adherent population (2013.1+1277.1 µg/l). Cardiac as well as severe liver iron overload was higher in the non-adherent patients. No correlation was found between disease knowledge and adherence to ICT. Difficulties in drug administration and many medicines to be taken daily were statistically significant reasons for non-adherence. There was no difference in the co-morbidities arising due to the iron overload in the two groups. Conclusion: Nearly 11% of patients with TDT were non-adherent to ICT. Non-adherence results in higher iron overload.

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