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Norbert Gattermann - One of the best experts on this subject based on the ideXlab platform.
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hematologic improvement with Iron Chelation therapy in myelodysplastic syndromes clinical data potential mechanisms and outstanding questions
Critical Reviews in Oncology Hematology, 2019Co-Authors: Heather A Leitch, Norbert GattermannAbstract:Abstract Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenias and progression to acute myeloid leukemia (AML). Although several treatments for MDS are available, the mainstay of therapy for most patients remains supportive care. This includes red blood cell (RBC) transfusion to correct anemia, which leads to Iron overload. RBC transfusion dependence and Iron overload portend inferior overall survival. Some studies indicate that Iron Chelation therapy (ICT) may have beneficial effects on clinical endpoints in MDS; however, these data are from non-randomized trials and the validity of the results is vigorously debated. A consistent observation in clinical studies of ICT in MDS has been hematologic improvement (HI) in some patients, including a reduction in RBC transfusion requirements and even transfusion independence. Here, we review data on HI with ICT in lower risk MDS, preclinical data examining mechanisms by which HI may occur, and identify areas for future investigation.
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corrigendum to when is Iron overload deleterious and when and how should Iron Chelation therapy be administered in myelodysplastic syndromes best pract res clin haematol 2013 431 444
Best Practice & Research Clinical Haematology, 2014Co-Authors: David P. Steensma, Norbert GattermannAbstract:Corrigendum to “When is Iron overload deleterious, and when and how should Iron Chelation therapy be administered in myelodysplastic syndromes?” [Best Pract Res Clin Haematol (2013) 431–444] David P. Steensma, MD, Associate Professor , Norbert Gattermann, MD, Associate Professor b,* Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA Klinik fur Hamatologie, Onkologie und Klinische Immunologie, Heinrich-Heine-Universitat, Moorenstr. 5, 40225 Dusseldorf, Germany
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when is Iron overload deleterious and when and how should Iron Chelation therapy be administered in myelodysplastic syndromes
Best Practice & Research Clinical Haematology, 2013Co-Authors: David P. Steensma, Norbert GattermannAbstract:Iron overload in MDS starts even before patients become red-blood cell transfusion dependent, because disease-associated ineffective erythropoiesis suppresses hepcidin production in the liver and thus causes unrestrained Iron absorption in the duodenum. However, the main cause of Iron overload is regular transfusion therapy, which in MDS is associated with a risk of unclear magnitude for Iron-related complications. Iron deposition in tissues can now be detected with non-invasive techniques such as T2* MRI. Iron toxicity in MDS may not only depend on the degree of tissue Iron accumulation but also on the extent of chronic exposure to non-transferrin-bound Iron (NTBI), including labile plasma Iron (LPI) and intracellular labile Iron pools, which increase the level of oxidative stress. Iron Chelation therapy (ICT) can rapidly lower NTBI and LPI and more slowly mobilizes tissue Iron stores. Further studies, including the ongoing TELESTO controlled trial, will more clearly define the role of ICT in MDS, including any effect on specific morbidities or mortality in the MDS setting.
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improved survival in mds patients receiving Iron Chelation therapy a matched pair analysis of 188 patients from the dusseldorf mds registry
Leukemia Research, 2012Co-Authors: Judith Neukirchen, Frank Fox, Andrea Kundgen, Kathrin Nachtkamp, Corinna Strupp, Rainer Haas, Ulrich Germing, Norbert GattermannAbstract:MDS patients are prone to develop transfusional Iron overload. Iron overload may partly explain why transfusion dependency is associated with a decreased likelihood of survival. Our matched-pair analysis included 94 patients on long-term Chelation therapy and 94 matched patients without it. All patients had Iron overload, defined as serum ferritin (SF) above 1000 ng/ml or a history of multiple transfusions and SF ≥ 500 ng/ml. Median SF was 1954 ng/ml in chelated and 875 ng/ml in non-chelated patients. The difference in median survival (74 vs. 49 months, respectively; p=0.002) supports the idea that Iron Chelation therapy is beneficial for MDS patients.
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overview of guidelines on Iron Chelation therapy in patients with myelodysplastic syndromes and transfusional Iron overload
International Journal of Hematology, 2008Co-Authors: Norbert GattermannAbstract:Between 2002 and 2008, a number of consensus statements and guidelines were developed by various groups around the world to educate healthcare professionals on the treatment of myelodysplastic syndromes (MDS), including the management of transfusional Iron overload with Iron Chelation therapy. Guidelines have been developed by The Italian Society of Hematology, The UK MDS Guidelines Group, The Nagasaki Group, The National Comprehensive Cancer Network, and The MDS Foundation. These guidelines show that the approaches to managing Iron overload in patients with MDS are region specific, differing in their recommendations for when Iron Chelation therapy should be initiated and strategies for the ongoing management of Iron overload. The guidelines all agree that red blood cell transfusions are clinically beneficial to treat the symptomatic anemia in MDS, and that patients with low-risk MDS receiving transfusions are the most likely to benefit from Iron Chelation therapy.
Heather A Leitch - One of the best experts on this subject based on the ideXlab platform.
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hematologic improvement with Iron Chelation therapy in myelodysplastic syndromes clinical data potential mechanisms and outstanding questions
Critical Reviews in Oncology Hematology, 2019Co-Authors: Heather A Leitch, Norbert GattermannAbstract:Abstract Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenias and progression to acute myeloid leukemia (AML). Although several treatments for MDS are available, the mainstay of therapy for most patients remains supportive care. This includes red blood cell (RBC) transfusion to correct anemia, which leads to Iron overload. RBC transfusion dependence and Iron overload portend inferior overall survival. Some studies indicate that Iron Chelation therapy (ICT) may have beneficial effects on clinical endpoints in MDS; however, these data are from non-randomized trials and the validity of the results is vigorously debated. A consistent observation in clinical studies of ICT in MDS has been hematologic improvement (HI) in some patients, including a reduction in RBC transfusion requirements and even transfusion independence. Here, we review data on HI with ICT in lower risk MDS, preclinical data examining mechanisms by which HI may occur, and identify areas for future investigation.
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delayed time from rbc transfusion dependence to first cardiac event in lower ipss risk mds patients receiving Iron Chelation therapy
Leukemia Research, 2019Co-Authors: Colleen A C Wong, Heather A LeitchAbstract:Abstract Transfused MDS patients are at risk for Iron overload (IOL). IOL may exacerbate congestive heart failure (CHF), coronary artery disease (CAD) and arrythmias (ARR). We retrospectively examined cardiac events (CE) in red blood cell (RBC) transfusion dependent (TD) lower IPSS risk MDS patients. Patients were censored at death or MDS progression. 151 MDS patients were lower IPSS risk and RBC TD. Median number of cardiac risk factors (RF) per patient was 1 (1–4). CE following RBC TD occurred in 48 (32%) and were: CHF, n = 20; CAD, n = 15; ARR, n = 11. In univariate analysis factors significant for time to (TT) CE were: age at 1st RBC transfusion; number of RBCU transfused while lower IPSS risk; received Iron Chelation therapy (ICT); MDS treatment received; and number of cardiac RF/patient (p ≤ 0.02). Receiving ICT remained significant for TTCE in multivariate analysis (p = 0.03). Median TTCE in patients not receiving and receiving ICT was 7.0 (0.1–65.0) and 20.0 (0.1–148.6) months, respectively (p = 0.02). For lower IPSS risk RBC transfusion dependent MDS patients, time to first cardiac event following RBC TD was significantly longer in patients receiving ICT. These results suggest ICT may delay cardiac events in transfused patients. The results should be confirmed in larger numbers in prospective analyses.
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controversies surrounding Iron Chelation therapy for mds
Blood Reviews, 2011Co-Authors: Heather A LeitchAbstract:The myelodysplastic syndromes (MDS) are characterized by cytopenias and acute myeloid leukemia risk. Most MDS patients eventually require transfusion of red blood cells for anemia, placing them at risk of Iron overload (IOL). In beta-thalassemia major, transfusional IOL leads to organ dysfunction and death, however, with Iron Chelation therapy survival improved to near normal and organ function was improved. In lower risk MDS, several non-randomized studies suggest an adverse effect of IOL on survival, and that lowering Iron minimizes this impact and may improve organ function. While guidelines for MDS generally recommend Chelation in selected lower risk patients, data are emerging suggesting IOL may impact adversely on the outcome of higher risk MDS and stem cell transplantation (SCT) and that lowering Iron may be beneficial in these patients. Trials to determine whether these effects are truly from lowering Iron are currently enrolling. Chelation is costly and potentially toxic, and in MDS should be initiated after weighing potential risks and benefits for each patient until more definitive data are available. In this paper, data on the impact of IOL in MDS and SCT, possible mechanisms of Iron toxicity such as oxidative stress, and the impact of lowering Iron on organ function and survival are reviewed.
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red blood cell transfusion independence following the initiation of Iron Chelation therapy in myelodysplastic syndrome
Advances in Hematology, 2010Co-Authors: Maha A Badawi, Linda M Vickars, Jocelyn M Chase, Heather A LeitchAbstract:Iron Chelation therapy is often used to treat Iron overload in patients requiring transfusion of red blood cells (RBC). A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional Chelation but subsequently accepted oral therapy. Following the initiation of Chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with Iron Chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of Iron Chelation on cytopenias are discussed.
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red blood cell transfusion independence following the initiation of Iron Chelation therapy in myelodysplastic syndrome
Blood, 2009Co-Authors: Maha A Badawi, Linda M Vickars, Jocelyn M Chase, Heather A LeitchAbstract: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 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.
David P. Steensma - One of the best experts on this subject based on the ideXlab platform.
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corrigendum to when is Iron overload deleterious and when and how should Iron Chelation therapy be administered in myelodysplastic syndromes best pract res clin haematol 2013 431 444
Best Practice & Research Clinical Haematology, 2014Co-Authors: David P. Steensma, Norbert GattermannAbstract:Corrigendum to “When is Iron overload deleterious, and when and how should Iron Chelation therapy be administered in myelodysplastic syndromes?” [Best Pract Res Clin Haematol (2013) 431–444] David P. Steensma, MD, Associate Professor , Norbert Gattermann, MD, Associate Professor b,* Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA Klinik fur Hamatologie, Onkologie und Klinische Immunologie, Heinrich-Heine-Universitat, Moorenstr. 5, 40225 Dusseldorf, Germany
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when is Iron overload deleterious and when and how should Iron Chelation therapy be administered in myelodysplastic syndromes
Best Practice & Research Clinical Haematology, 2013Co-Authors: David P. Steensma, Norbert GattermannAbstract:Iron overload in MDS starts even before patients become red-blood cell transfusion dependent, because disease-associated ineffective erythropoiesis suppresses hepcidin production in the liver and thus causes unrestrained Iron absorption in the duodenum. However, the main cause of Iron overload is regular transfusion therapy, which in MDS is associated with a risk of unclear magnitude for Iron-related complications. Iron deposition in tissues can now be detected with non-invasive techniques such as T2* MRI. Iron toxicity in MDS may not only depend on the degree of tissue Iron accumulation but also on the extent of chronic exposure to non-transferrin-bound Iron (NTBI), including labile plasma Iron (LPI) and intracellular labile Iron pools, which increase the level of oxidative stress. Iron Chelation therapy (ICT) can rapidly lower NTBI and LPI and more slowly mobilizes tissue Iron stores. Further studies, including the ongoing TELESTO controlled trial, will more clearly define the role of ICT in MDS, including any effect on specific morbidities or mortality in the MDS setting.
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the relevance of Iron overload and the appropriateness of Iron Chelation therapy for patients with myelodysplastic syndromes a dialogue and debate
Current Hematologic Malignancy Reports, 2011Co-Authors: David P. SteensmaAbstract:Accumulation of excessive amounts of Iron in vulnerable organs and tissues, together with elevated plasma and intracellular concentrations of reactive Iron molecules, are likely to be harmful to some patients with myelodysplastic syndromes (MDS) who have received numerous red blood cell transfusions. But what is the real magnitude of risks related to Iron overload in MDS, and how strong is the evidence that reducing total body Iron and labile plasma Iron through treatment with chelating drugs is beneficial to patients? Available data can be interpreted in different ways, and as a result, these topics continue to be areas of heated debate among physicians who care for patients with MDS. Using the traditional but rarely employed format of a classical dialogue, I explore here the potential dangers of Iron overload and the risks and benefits of Iron Chelation therapy for patients with MDS.
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The role of Iron Chelation therapy for patients with myelodysplastic syndromes.
Journal of the National Comprehensive Cancer Network : JNCCN, 2011Co-Authors: David P. SteensmaAbstract:The appropriate role of Iron Chelation therapy in the management of patients with myelodysplastic syndromes (MDS) is currently controversial. Some investigators interpret data to indicate that careful attention to Iron parameters, with early initiation of Iron Chelation in patients with evidence suggesting transfusion-associated Iron overload, is an important component of high-quality MDS patient care. Other physicians are more skeptical, noting that Chelation can be cumbersome or costly, has associated risks, and has not yet been shown to reduce morbidity or mortality in the MDS setting. This article reviews the extent to which Iron Chelation therapy might be either an important clinical intervention in MDS or a distraction from more pressing clinical concerns.
Guillermo Sanz - One of the best experts on this subject based on the ideXlab platform.
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impact of treatment with Iron Chelation therapy in patients with lower risk myelodysplastic syndromes participating in the european mds registry
Haematologica, 2020Co-Authors: Marlijn Hoeks, Saskia Langemeijer, Simon Crouch, Louise De Swart, Pierre Fenaux, Argiris Symeonidis, Jaroslav Cermak, Eva Hellstromlindberg, Guillermo SanzAbstract:Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after Iron Chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting Iron Chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of Chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received Iron Chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that Iron Chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860.
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evolution of Iron overload in patients with low risk myelodysplastic syndrome Iron Chelation therapy and organ complications
Annals of Hematology, 2015Co-Authors: Angel F Remacha, Beatriz Arrizabalaga, A Villegas, Maria Soledad Duran, Lourdes Hermosin, Raquel De Paz, M A Garcia, Maria Diez Campelo, Guillermo SanzAbstract:This study aimed to evaluate the evolution of Iron overload, assessed by serum ferritin (SF), in transfusion-dependent lower risk patients with myelodysplastic syndrome (MDS), as well as to describe the occurrence of organ complications, and to analyze its relationship with Iron Chelation therapy. This observational retrospective study was conducted from March 2010 to March 2011 in 47 Spanish hospitals. A total of 263 patients with lower risk MDS (International Prognostic Scoring System [IPSS] low/intermediate-1 risk or Spanish Prognostic Index [SPI] 0–1 risk), transfusion-dependent, and who had received ≥10 packed red blood cells (PRBC) were included. At MDS diagnosis, patients received a mean of 2.8 ± 3.9 PRBC/month, and 8.7 % of patients showed SF ≥1000 μg/L. Over the course of the disease, patients received a mean of 83.4 ± 83.3 PRBC, and 36.1 % of patients presented SF ≥2500 μg/L. Cardiac, hepatic, endocrine, or arthropathy complications appeared/worsened in 20.2, 11.4, 9.9, and 3.8 % of patients, respectively. According to investigator, Iron overload was a main cause of hepatic (70.0 %) and endocrine (26.9 %) complications. A total of 96 (36.5 %) patients received Iron Chelation therapy for ≥6 months, being deferasirox the most frequent first Chelation treatment (71.9 %). Chelation-treated patients showed longer overall survival (p < 0.001), leukemia-free survival (p = 0.007), and cardiac event-free survival (p = 0.017) than non-chelated patients. In multivariable analyses, age (p = 0.011), IPSS (p < 0.001), and Chelation treatment (p = 0.015) were predictors for overall survival; IPSS (p = 0.014) and transfusion frequency (p = 0.001) for leukemia-free survival; and Chelation treatment (p = 0.040) and Sorror comorbidity index (p = 0.039) for cardiac event-free survival. In conclusion, these results confirm the potential survival benefit of Iron Chelation therapy and provide additional evidence on the deleterious effect of Iron overload in lower risk MDS patients.
Emanuele Angelucci - One of the best experts on this subject based on the ideXlab platform.
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Iron Chelation in transfusion dependent patients with low to intermediate 1 risk myelodysplastic syndromes
Annals of Internal Medicine, 2020Co-Authors: Emanuele Angelucci, Peter L Greenberg, Miguel Izquierdo, Guillermo GarciamaneroAbstract:Iron overload in transfusion-dependent patients with myelodysplastic syndrome (MDS) can lead to poorer clinical outcomes. The effectiveness of Iron Chelation therapy in patients with lower-risk MDS...
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Iron Chelation in transfusion dependent patients with low to intermediate 1 risk myelodysplastic syndromes a randomized trial
Annals of Internal Medicine, 2020Co-Authors: Emanuele Angelucci, Peter L Greenberg, Miguel Izquierdo, Guillermo Garciamanero, Ming Hou, Efreen Montano Figueroa, Maria Guadalupe Rodriguez, Xunwei Dong, Jagannath Ghosh, Telesto Study InvestigatorsAbstract:Background Iron Chelation therapy (ICT) in patients with lower-risk myelodysplastic syndromes (MDS) has not been evaluated in randomized studies. Objective To evaluate event-free survival (EFS) and safety of ICT in Iron-overloaded patients with low- or intermediate-1-risk MDS. Design Multicenter, randomized, double-blind, placebo-controlled trial (TELESTO). (ClinicalTrials.gov: NCT00940602). Setting 60 centers in 16 countries. Participants 225 patients with serum ferritin levels greater than 2247 pmol/L; prior receipt of 15 to 75 packed red blood cell units; and no severe cardiac, liver, or renal abnormalities. Intervention Deferasirox dispersible tablets (10 to 40 mg/kg per day) (n = 149) or matching placebo (n = 76). Measurements The primary end point was EFS, defined as time from date of randomization to first documented nonfatal event (related to cardiac or liver dysfunction and transformation to acute myeloid leukemia) or death, whichever occurred first. Results Median time on treatment was 1.6 years (interquartile range [IQR], 0.5 to 3.1 years) in the deferasirox group and 1.0 year (IQR, 0.6 to 2.0 years) in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years [95% CI, 3.2 to 4.3 years] vs. 3.0 years [CI, 2.2 to 3.7 years], respectively; hazard ratio, 0.64 [CI, 0.42 to 0.96]). Adverse events occurred in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure-adjusted incidence rates of adverse events (≥15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarrhea, 21.8 versus 18.7 for pyrexia, 16.7 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration. Limitations The protocol was amended from a phase 3 to a phase 2 study, with a reduced target sample size from 630 to 210 participants. There was differential follow-up between treatment groups. Conclusion The findings support ICT in Iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinically manageable safety profile. Therefore, ICT may be considered in these patients. Primary funding source Novartis Pharma AG.
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marrow transplantation in patients with thalassemia responsive to Iron Chelation therapy
The New England Journal of Medicine, 1993Co-Authors: Guido Lucarelli, Emanuele Angelucci, Maria Galimberti, P Polchi, D Baronciani, C Giardini, Marco Andreani, F Agostinelli, F Albertini, R A CliftAbstract:Background Patients with homozygous beta-thalassemia, who have a good prognosis during treatment with conventional therapy, appear to have an especially high probability of hematologic cure with bone marrow transplantation, although the morbidity and mortality associated with such treatment are not established. Methods The records of all patients with thalassemia who received bone marrow transplants from HLA-identical donors in Pesaro, Italy, were examined from October 1982 through May 1992. Detailed evaluation of the outcome was conducted in the 89 patients identified as being in class 1 according to the Pesaro classification, in which hepatomegaly, portal fibrosis, and the inadequacy of Iron Chelation therapy are considered independent risk factors, and the patients are classified as being in class 1 if none of these factors are present, class 2 if one or two of the factors are present, and class 3 if all three factors are present. Sixty-four of the patients had been prepared for transplantation with a ...