Improving clinical outcome in patients with myelodysplastic syndrome and iron overload using iron chelation therapy

2007 ◽  
Vol 31 ◽  
pp. S7-S9 ◽  
Author(s):  
Heather A. Leitch
Keyword(s):  
Clinical Outcome ◽  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy

Effectiveness, Time Utilization and Clinical Outcome of Partial Manual Red Cell Exchange in Patients with Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2326-2326
Author(s):  
Kevin H.M. Kuo ◽  
David Barth ◽  
Richard Ward
Keyword(s):  
Sickle Cell Disease ◽  
Clinical Outcome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Venous Access ◽  
Iron Chelation Therapy ◽  
Red Cell ◽  
Cell Disease ◽  
Hemoglobin S

Abstract Abstract 2326 Introduction: Red cell exchange transfusion (RBCX) is used to treat and prevent selected complications from Sickle Cell Disease (SCD) where there is a need to reduce hemoglobin S level, blood viscosity, improve oxygen carrying capacity, and to avoid rapid iron overload from simple transfusions. Partial manual red cell exchange is sometimes employed in the chronic maintenance of low hemoglobin S levels. Data on the efficacy and clinical outcome of SCD patients on partial manual RBCX are limited. Methods: All partial manual RBCX from the University Health Network, a SCD comprehensive care center between April 1st, 2010 and April 30th, 2011 were retrospectively reviewed. Patients were exchanged at a frequency of 4 to 6 weeks where each session consists of two 500cc phlebotomy with an infusion of 500cc normal saline in between the phlebotomies, and transfusion of 2 units of packed red cells (pRBC). The procedure was repeated until pre-RBCX hemoglobin S (HbS) level <50% was reached (for patients without overt stroke for >4 years). Phlebotomy was reduced or omitted during episodes of symptomatic anemia at the discretion of the treating hematologist. Patients with poor venous access had indwelling line with chronic, therapeutic anticoagulation against line-related thrombosis. Results: Nineteen patients (16 HbSS, 2 HbSC, 1 HbSD) totalling 176 exchange sessions were reviewed. Indications for RBCX include primary and secondary stroke prevention (n = 14), recurrent painful vaso-occlusive crises intolerant or refractory to hydroxyurea (n = 3), pulmonary hypertension confirmed on right heart catheterization with hypoxia (n = 1), and prevention of intrahepatic cholestasis in a liver allograft (n = 1). Mean frequency of RBCX was 4.8 weeks (95% CI 3.9, 5.6 weeks). There were 2 transfusion-related (fever, pruritis) and 1 phlebotomy-related (pre-syncope) adverse events. There were 23 partial/cancelled phlebotomy sessions, mostly due to symptomatic anemia. Mean post-RBCX hematocrit was 0.296 (95% CI 0.280, 0.312) and pre-RBCX HbS level was 0.439 (95% CI 0.387, 0.490). Pre-RBCX HbS level of <50% was achieved in 74% of exchanges. Reasons for not achieving the target HbS level include: exchange interval >4.0 weeks, not on any transfusion regime prior to initiating partial manual RBCX, reduced or no phlebotomy in previous session, and non-adherence to treatment. Patients who were adherent to treatment had no recurrent events related to their initial indication for RBCX (one patient has possible Moyamoya formation but no clinically overt stroke), while 3 of the 6 patients who were not adherent had events during the study period (2 had painful vaso-occlusive crisis requiring hospital admission and 1 had new Moyamoya-like changes on cerebral angiogram). It took a median time of 90 minutes to phlebotomize 1,000cc whole blood and 176 minutes to transfuse two units of pRBC. There was no significant difference between the time required to phlebotomize or transfuse via peripheral vein versus an indwelling line (55 vs. 53 minutes/500cc; P = 0.7572 and 88 minutes vs. 88 minutes/unit; P = 0.9859). Eleven patients were also on iron chelation therapy for iron overload from previous simple transfusion, and patients who were adherent to RBCX (n = 7) had either a stable or reduction in ferritin level. Discussion: Patients who are adherent on partial manual RBCX can maintain a pre-RBCX HbS <50% with good clinical outcomes and low rates of adverse events, reduced blood consumption compared to automated RBCX, and obviate the need for ongoing iron chelation in those without pre-existing iron overload. In patients with iron overload, RBCX combined with iron chelation therapy can maintain iron balance. In patients with good peripheral venous access, indwelling lines do not confer an advantage to the speed of phlebotomy or transfusion. Patient with pre-RBCX HbS level >50% may benefit from a single session of automated RBCX to “reset” their HbS level before commencing chronic partial manual RBCX. Further prospective studies will aim to determine the rate of new or progressive silent infarcts and vasculopathy and reduction of iron balance via partial manual RBCX. Disclosures: Kuo: Novartis Canada: Research Funding.

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.

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

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.

Iron Chelation Therapy in CAPD: A New and Effective Treatment of Iron Overload Disease in Esrd Patients

1983 ◽  
Vol 3 (2) ◽  
pp. 99-101 ◽  
Author(s):  
Glen H Stanbaugh ◽  
A. W, Holmes Diane Gillit ◽  
George W. Reichel ◽  
Mark Stranz
Keyword(s):  
Peritoneal Dialysis ◽  
Iron Overload ◽  
End Stage Renal Disease ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Peritoneal Dialysate ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

A patient with end-stage renal disease on CAPD, and with massive iron overload is reported. This patient had evidence of myocardial and hepatic damage probably as a result of iron overload. Treatment with desferoxamine resulted in removal of iron in the peritoneal dialysate. On the basis of preliminary studies in this patient it would appear that removal of iron by peritoneal dialysis in conjunction with chelation therapy is safe and effective. This finding should have wide-ranging signficance for patients with ESRD.

scholarly journals Iron Chelation and Ferritin below 500 Mcg/L in Transfusion Dependent Thalassemia: Beyond the Limits of Clinical Trials

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3542-3542 ◽  
Author(s):  
Natalia Scaramellini ◽  
Carola Arighi ◽  
Alessia Marcon ◽  
Dario Consonni ◽  
Elena Cassinerio ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Liver Function ◽  
Iron Overload ◽  
Board Of Directors ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Published Data ◽  
Iron Chelation Therapy ◽  
Iron Intake ◽  
Advisory Committees

Introduction The current therapeutic management of transfusion dependent thalassemia (TDT) is based on regular blood transfusion and iron chelation therapy. Transfusion iron overload remains one of the major causes of morbidity and mortality in these patients because of the accumulation in heart, liver and endocrine glands. Three iron chelators are available in clinical practice: deferoxamine (DFO), deferiprone(DFP) and deferasirox (DFX). Guidelines clearly recommend when to start iron chelation, while discontinuation criteria are not well defined. Authorised product information state that we should consider interrupting DFX if serum ferritin (SF) falls consistently below 500mcg/L. This cut off was arbitrarily determined and there are no studies evaluating the effects of chelators in presence of SF below 500 mcg/L. In our clinical practice at Rare Diseases center of Fondazione IRCCS Ca' Granda Policlinico in Milan we do not completely interrupt iron chelation in TDT patients for SF levels below 500 mcg/L. Aims and methods Aim of our study was to evaluate the appearance of adverse events due to the assumption of iron chelation therapy in those TDT patients who had SF below 500 mcg/L. In this study we retrospectively evaluated renal and liver function from 2008 throughout December 2018 in TDT patients on DFX who presented SF below 500 mcg/L for 24 consecutive months. DFX dose are all expressed with the new tablets formulation dose. We evaluated SF, iron intake, LIC and MIC, renal and hepatic function. .A total of 5076 observations were collected, with 99.5 average per patient. We evaluated the relationships among variables with correlation models with random intercept Results One hundred ninety-two TDT patients are regularly followed at our center. They receive regular transfusion treatment and iron chelation therapy to prevent secondary iron overload. 51 out of 192 patients (32 F, 19 M, aged 44 ± 7 years) treated with DFX presented mean SF below 500 mcg/L for at least 24 consecutive months. Hematological and iron status parameters are described in Table 1. We found a strong correlation between SF and LIC (p&lt;0.001) and for SF&lt;500 mcg/L no hepatic iron overload was observed. Conversely we did not found a correlation between SF and MIC. For SF values below 500 mcg/L there was a minimal increase in creatinine levels, however the mean creatinine values remained within the normal range.Moreover, creatinine variation between two consecutive evaluation was below 0.3 mg/dl, cut off for acute kidney injury. Similar results were observed for liver function. Although a minimal increase of mean ALT value was observed for SF below 500 mcg/L, it remained within the normal range. None of our patient showed ALT level indicative of liver damage (ALT&gt; 10 x upper limit of normal) We evaluated the relation between SF and DFX dose. Mean DFX dose decreases according to SF reduction. However, for SF value &lt; 240 mcg/L, DFX dose remained stable at an average of 14 mg/kg per day. Conclusion According to our preliminary data, administration of DFX in TDT patients in presence of SF below 500 mcg/L is safe. Creatinine and ALT fluctuations, that usually remain within the range of normality, are mild, and transient and do not require specific treatment. Consistently with previously published data by Cohen et al, we show that a mean dosage of DFX of 14 mg/Kg die of film-coated tablet (20 mg/Kg of dispersable formulation) are necessary to balance an iron intake of 0.3 mg/kg die in absence of iron overload. Based on these results we suggest that in TDT patients with a continuous iron intake, iron chelation should be continued even when ferritin is below 500mcg/L. Monitoring of liver and kidney function tests are recommended in patient's follow up, as well as tailoring iron chelation. Disclosures Cappellini: Vifor Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees; Genzyme/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Motta:Sanofi-Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4844-4844
Author(s):  
Maha A Badawi ◽  
Linda M Vickars ◽  
Jocelyn M Chase ◽  
Heather A Leitch
Keyword(s):  
Platelet Count ◽  
Myelodysplastic Syndrome ◽  
Research Funding ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Transfusion Independence ◽  
Transfusion Requirements ◽  
Rbc Transfusion

Abstract Abstract 4844 Background Iron chelation therapy (ICT) is often used to treat iron overload (IOL) in patients (pts) requiring transfusion of red blood cells (RBC) for chronic anemia. In myelodysplastic syndrome (MDS), guidelines recommend consideration of ICT in pts with lower risk International Prognostic Scoring System (IPSS) and IOL as defined by a ferritin level >1000 ug/l; IOL related organ dysfunction; or receipt of ≥20 RBC units. During treatment of a pt with MDS and IOL with ICT, RBC transfusion requirement (TR) ceased. Here we report his course and review reported cases of RBC transfusion independence (TI) or decreased RBC TR in MDS pts receiving ICT. Methods The pt chart was reviewed and reported cases identified by PubMed search using the terms ‘MDS’ and ‘iron chelation’. The clinical characteristics and course of published cases were summarized. Case A 76 year (y) old man was referred in May 2004 for management of MDS diagnosed in 1997, when the white blood cell (WBC) count was 2.4 ×109/l; neutrophils, 0.7 ×109/l; hemoglobin (Hb), 133 g/l; platelets, 108 ×109/l. Bone marrow aspiration and biopsy showed refractory anemia (RA), karyotype analysis 46,X,-Y,+8, and the IPSS score was intermediate-1. The erythropoitin (epo) level was 148.3 mIU/ml and the stem cell assay showed no epo-independent colony growth. In 2004 the Hb dropped to 60 g/l prompting the initiation of RBC transfusion support. He required 3 RBC units every 4 weeks to maintain a Hb >90 g/l and complained of fatigue and functional limitation. Creatinine, bilirubin, TSH, reticulocyte count, B12 and folate levels were all normal. The ferritin level in 2004 was 1293 ug/l and 2197 ug/l in 2006. He declined ICT with deferoxamine (DFO) but in 2006 accepted deferasirox (DFX). He required several dose interruptions and adjustments for renal insufficiency; the current dose is 5mg/kg/d with a normal creatinine. Two months (mo) after starting ICT, the Hb increased spontaneously to 109 g/l and he has not required RBC transfusion since. The mean Hb since starting ICT was 122 g/l and the ferritin decreased to 1082 ug/l in 2009. The most recent neutrophil count was 3.5 ×109/l, platelets consistently clump and the MCV is unchanged at 120 fl. He reports excellent energy and an improved quality of life, and has remained clinically well and RBC transfusion independent to the present, 36 mo from the initiation of ICT. Literature review There are 18 published cases of MDS showing improvement in Hb with ICT; 9 became RBC transfusion independent. Characteristics of the 10 TI pts were: median age at MDS diagnosis 58 (range 18-74) y; male, n=5. MDS subtype: RA, n=5; RARS, n=2, RCMD, n=1; RAEB, n=2. IPSS (reported in 8): low, n=1; int-1, n=5; int-1 or 2, n=1; high, n=1. ICT was: DFO, n=7; DFX, n=3. Median time to RBC TI was 17.5 (1-24) mo and TI duration 13 (3-28) mo to date. Of pts who had decreased RBC transfusion requirements with ICT but did not achieve transfusion independence: median age (reported in 3) was 67 (45-78) y; gender (reported in 3) female, n=3; MDS subtype: RA, n=8; RAEB-t, n=1; IPSS: int-1, n=3; ICT: DFO, n=8; DFX, n=1. Median time to decreased TR was 14.4 (3-24) mo; median duration of decreased TR (reported in 3) 9 (6-32) mo; initial TR 50.9 (19.7-447) g Hb/mo; median decrease in TR 12.7 (0.1-88) g Hb/mo. In one report of 6 pts, 2 with pancytopenia showed improvement with ICT in WBC from 1.4 to 1.9 ×109/l (p<0.0001) and neutrophils from 0.51 to 0.94 ×109/l (p<0.001). The platelet count increased from 16.6 to 22.5 ×109/l (p<0.001) and 14.6 to 29.6 ×109/l (p<0.00001) within 3 mo and the MCV decreased significantly in 5 by a mean of 5.1 (2.1-11.7) fl, normalizing in 2. In a second report, neutrophils increased in 8 of 9 pts; in 4 the initial neutrophil count was <1 ×109/l, and platelet counts increased in 7 of 11 pts, in 4 the initial platelet count was <20 ×109/l. Conclusions In summary, our pt is the 19th patient with MDS reported to date in whom improved Hb followed the initiation of ICT; 9 had a decrease in RBC transfusion requirements, and RBC transfusion independence occurred in 10. The remarkable course of these pts adds to evidence that ICT may be of clinical benefit for selected patients with MDS and IOL. Although the improvement in WBC and platelet counts with ICT in some pts implies a suppressive effect of IOL on hematopoiesis that may be abrogated by ICT, the mechanism by which the effects of ICT on transfusion requirements occur, and the frequency with which they occur, remains an area for future investigation. Disclosures Off Label Use: This presentation discusses the use of iron chelation therapy deferoxamine and deferasirox in patients with myelodysplastic syndrome.. Vickars:Novartis Canada: Honoraria, Research Funding. Leitch:Novartis Canada: Honoraria, Research Funding, Speakers Bureau.

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