scholarly journals The impact of iron chelation therapy on patients with lower/intermediate IPSS MDS and the prognostic role of elevated serum ferritin in patients with MDS and AML

Medicine ◽  
2019 ◽  
Vol 98 (40) ◽  
pp. e17406 ◽  
Author(s):  
Yuan Yang ◽  
Zengwei Tang ◽  
Tianli An ◽  
Li Zhao
Keyword(s):  
Serum Ferritin ◽  
Chelation Therapy ◽  
Elevated Serum ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Prognostic Role ◽  
The Impact

Impact of Iron Chelation Therapy on Overall Survival and AML Transformation in Lower Risk MDS Patients Treated At the Moffitt Cancer Center

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2776-2776 ◽  
Author(s):  
Rami S. Komrokji ◽  
Najla H Al Ali ◽  
Eric Padron ◽  
Jeffrey E. Lancet ◽  
Alan F. List
Keyword(s):  
Overall Survival ◽  
Serum Ferritin ◽  
Lower Risk ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Elevated Serum ◽  
Iron Chelation ◽  
Cancer Center ◽  
Baseline Characteristics ◽  
The Impact

Abstract Abstract 2776 Background: Elevated serum ferritin levels and red blood cell transfusion dependence are associated with poor outcome in patients with lower risk myelodysplastic syndromes (MDS). Few retrospective and observational studies suggest that iron chelation therapy (ICT) may favorably impact outcome in lower risk MDS. The vast majority of patients in those studies were treated with deferoxamine (Desferal). Two studies reported that oral deferasirox (Exjade) significantly decreases ferritin level over time in MDS. An ongoing randomized placebo-controlled trial (TELESTO) is designed to address the impact of deferasirox on overall survival (OS) in lower risk MDS. We examined the impact of ICT predominantly deferasirox in lower risk MDS patients treated at the Moffitt Cancer Center (MCC). Methods: Patients were retrospectively identified from the MCC database and individual patients' records reviewed. Inclusion criteria included lower risk MDS patients defined as low or intermediate-1 (int-1) risk disease by the international prognostic scoring system (IPSS) and serum ferritin level ≥ 1000 ng/ml. Patients were divided into two comparator groups: ICT vs. no ICT. Baseline characteristics were compared between the two groups; chi square test was used for categorical variables and t-test for continuous variables. The primary endpoint was overall survival compared between the two groups using Kaplan-Meier estimates. Cox regression was used for multivariate analysis. All analyses were conducted using SPSS version 19.0 statistical software. Results: Between July 2001 and July 2009, 97 patients with lower risk MDS and serum ferritin ≥ 1000 ng/ml were identified. Forty five (46.4%) received ICT and 52 did not. The ICT included deferasirox in 35 patients and deferoxamine in 10 patients. The baseline characteristics between the two groups (ICT and no ICT) are summarized in (table-1). No statistically significant difference in baseline characteristics was observed except more patients in the ICT group were transfusion dependent. The median duration of follow up was 85.7 month from time of diagnosis. The median OS was 59 months (95%CI 22–48) for patients who received ICT compared to 33.7 months (95%CI 38–80) for patients who did not receive ICT (P= 0.013). After adjustment for age and cytogenetics in Cox multivariable analysis, ICT was associated with better OS (HR 0.52, 95%CI 0.31–0.87, P= 0.013). The rate of AML transformation was 21.2% in patients who did not receive ICT compared to 15.6% in those who had ICT. (p=0.33). Conclusion: ICT in lower risk MDS patients with elevated serum ferritin ≥ 1000 ng/ml was associated with improved overall survival and a trend to lower AML transformation. Results of ongoing randomized clinical study with deferasirox are needed to confirm the retrospective data. Disclosures: Komrokji: Novartis: Honoraria, Research Funding.

Clinical Parameters in 391 Iron-Overloaded Patients with Lower-Risk MDS Enrolled in a Prospective, Non-Interventional Multicenter Registry.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4834-4834
Author(s):  
Guillermo Garcia-Manero ◽  
Billie J. Marek ◽  
Roger M. Lyons ◽  
Noelia Martinez-Lopez ◽  
Carole Paley ◽  
...  
Keyword(s):  
Iron Overload ◽  
Board Of Directors ◽  
Serum Ferritin ◽  
Lower Risk ◽  
Research Funding ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Advisory Committees ◽  
The Impact

Abstract Abstract 4834 Introduction Despite recent improvements in therapies for patients with myelodysplastic syndromes (MDS), 60–80% will require continuing packed red cell blood (pRBC) transfusions for prolonged periods. Complications resulting from the iron burden may, therefore, become clinically significant for many patients during the course of their disease. Patients with lower-risk MDS have a greater chance of developing the long-term toxicity of iron overload because of their prolonged survival, and are more likely to benefit from effective iron chelation therapy. This report describes data from a registry designed to study the impact of iron overload and iron chelation therapy on organ function and survival in patients with lower-risk MDS. Methods This is an ongoing, prospective, non-interventional, multicenter 5-year registry in 107 US centers, enrolling 600 patients (aged ≥18 years) with lower-risk MDS (by WHO, FAB and/or IPSS criteria) and transfusional iron overload (defined as serum ferritin ≥1000 μg/L and/or having received ≤20 cumulative pRBC units and/or an ongoing transfusion requirement ≥6 units every 12 weeks). Follow-up will be performed at least every 6 months for a maximum of 60 months or until death. Recommended assessments include serum ferritin, creatinine, calculated creatinine clearance, echocardiograms, and endocrine and hematological status. Results As of May 31 2009, 391 patients have enrolled in the registry. Demographic data are available from 389 patients. Median age: 74.4 years (range 21–99); male: 218, female: 171; ethnicity: 331 Caucasian (85%), 25 African-American (6%), 24 Hispanic (6%), five Asian (1%), two Native American (0.5%), and two other (0.5%). The median time since diagnosis (n=385) was <3 years in 217 patients (56%); ≥3–<5 years in 72 (19%); ≥5–<7 years in 48 (12%); and ≥7 years in 48 (12%). The MDS classification of the patients by WHO, FAB and IPSS, as well as patients' serum ferritin and transfusion burden, are summarized in the table. The most frequent concomitant conditions classified by organ (n=384 patients) were: 205 (53%) patients with vascular, 160 (42%) endocrine, and 171 (45%) cardiac dysfunction. At registry entry, 249 patients were receiving erythropoietin; 61 granulocyte colony stimulating factor; seven hydroxyurea; 25 thalidomide (Thalomid); 147 5-azacytidine (Vidaza); 95 lenalidomide (Revlimid) and 90 decitabine (Dacogen). 137 of 391 (35%) patients were on iron chelation therapy at study entry: 34 (9%) received deferoxamine for mean and median treatment durations of 803 and 383 (range 1–4386) days, respectively, while 117 (30%) received deferasirox for mean and median durations of 488 and 396 (9–1269) days, respectively. Calculated creatinine clearance was normal (>80 mL/min) in 37 (9%) patients; mildly abnormal (51–80 mL/min) in 30 (8%); and moderately abnormal (30–50 mL/min) in nine (2%) patients. Conclusions These baseline data indicate the demographic distribution as well as the co-morbidities associated with lower-risk MDS patients. In spite of recent guidelines, fewer than 50% of iron-overloaded patients are receiving any iron chelation treatment, despite the presence of cardiac, vascular and endocrine concomitant conditions in 40-54% of patients. Recent retrospective data highlights the impact of chelation on mortality in lower-risk MDS patients. This ongoing registry will prospectively assess the impact of iron chelation on survival and organ function in iron-overloaded patients with lower-risk MDS. Disclosures Lyons: Novartis: Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genzyme: Research Funding. Martinez-Lopez:Novartis Pharmaceuticals: Employment. Paley:Novartis Pharmaceuticals: Employment, Equity Ownership. Greenberg:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Effects of Leucine Administration in Diamond-Blackfan Anemia Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1686-1686
Author(s):  
Dagmar Pospisilova ◽  
Jana Cmejlova ◽  
Tomas Adam ◽  
Radek Cmejla
Keyword(s):  
Dose Reduction ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Steroid Treatment ◽  
Translational Efficiency ◽  
Iron Chelation Therapy ◽  
Gradual Improvement ◽  
Diamond Blackfan Anemia ◽  
Steroid Dose

Abstract Diamond-Blackfan anemia (DBA) attracts much attention, since the symptoms of the disease are associated with mutations in ribosomal protein (RP) S19 in 25% of patients and in RPS17 and RPS24 in other DBA patients, indicating a possible relationship between ribosomal function, translation level and erythropoiesis. Indeed, translational efficiency has been found to be lowered in most DBA patients, and the amino acid leucine was tested in vitro as a potential modulator of protein synthesis with promising results. We therefore decided to evaluate the effects of leucine administration in several DBA patients. For leucine therapy, 4 patients with the lowest levels of translation (patients 1, 2, 4 and 6; see Table) and 2 others were selected from the Czech DBA registry. Due to iron overload, all patients were receiving iron chelation therapy at the start of the leucine therapy. A total dose of 2000 mg/m2/day of L-leucine was administered orally in three subdoses in the form of a capsule prepared by the hospital pharmacy. The doses were based on the leucine content in sports dietary protein supplements, and reduced according to each patient’s body surface area. Two and 4 hours after administration, serum leucine levels doubled, but did not exceed normal values. Changes in other amino acids serum levels were not observed. After 8 weeks of leucine supplementation, all patients reported a noticeable increase in appetite and weight gain. Over a period of 6 months of follow-up, a gradual improvement in reticulocyte counts, hemoglobin levels and a reduction of serum ferritin levels were observed in all patients (see Table). One patient became transfusion independent, and is currently still in remission (>5 months); in two other transfusion dependent patients, the inter-transfusion period doubled; in steroid-dependent patients, the steroid dose could be reduced. The patient with the RPS17 mutation significantly improved in weight and well-being, and the iron chelation therapy was stopped. Our results thus show for the first time that leucine administration can greatly improve the quality of life of DBA patients in at least two ways - it can reduce the need for iron chelation; and it can gradually enhance erythropoiesis, reducing the steroid dose or the frequency of transfusions. Patients’ characteristics Patient No. Age (y) / Sex Status before Leu Level of translation (% of controls)* Duration of Leu administration (mo) Serum ferritin level before Leu/current (μg/l) Reticulocyte count before Leu/current (%) Effect of Leu administration MUT: mutation in RPS17; NM: no mutation in RPS17, RPS19 or RPS24; TD: transfusion dependent; HDS: high dose steroid treatment; LDS: low dose steroid treatment; ND: not done; PTP: prolongation of the transfusion period (before Leu/ current); *: Haematologica91:1456(2006) 1 NM 7 / F TD 21 12 1220 / 381 0.1 / 3.3 Remission 2 NM 8 / M TD 47 9 1311 / 492 0.1 / 0.4 PTP (3 / 6 weeks) 3 NM 11 / F TD ND 2 1950 / ND 0.1 / ND Increased appetite 4 MUT 31 / M LDS 39 8 860 / 496 1.1 / 1.5 Steroid dose reduction 5 NM 13 / M TD 77 6 1427 / 1110 0.6 / 1.4 PTP (4 / 8 weeks) 6 NM 18 / M HDS 42 12 1605 / 862 0.4 / 0.8 Steroid dose reduction

The Palatability and Tolerability of Deferasirox (Exjade®) Taken with Meals, Different Liquids, or Crushed and Added to Food

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5155-5155
Author(s):  
Stuart L Goldberg ◽  
Patricia Giardina ◽  
Joan Parkhurst Cain ◽  
Deborah Chirnomas ◽  
Jason Esposito ◽  
...  
Keyword(s):  
Adverse Events ◽  
Serum Ferritin ◽  
Research Funding ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Iron Chelation Therapy ◽  
Age Group ◽  
Baseline Serum ◽  
Off Label

Abstract Abstract 5155 Introduction: Deferasirox (Exjade®, Novartis Pharmaceuticals) is an oral iron chelator indicated for the treatment of transfusional iron overload. The recommended mode of administration is to be taken on an empty stomach in water, apple juice or orange juice ≥30 minutes before food. However, there have been post-marketing reports of discontinuation or reduced compliance of deferasirox secondary to palatability and gastrointestinal adverse events. Registration trials with deferasirox did not evaluate different food combinations in an attempt to maintain predictable plasma levels. Early single dose studies suggested that the bioavailability of deferasirox is increased when administered with or before meals, and is positively influenced by fat content, but is not affected by degree of dispersion nor type of liquid. Long-term pharmacokinetic and tolerability studies involving a food effect have not been conducted to date, and the ability of alternate methods of administration to improve patient compliance with iron chelation therapy is unknown. Method: This is an ongoing single-arm, open-label, multi-center study designed to evaluate the palatability, safety, tolerability and pharmacokinetics of deferasirox when administered with food, dispersed in any liquid of choice, or crushed and added to food. The patient population includes patients with transfusional hemosiderosis (minimum entry serum ferritin ≥500 μ g/L) aged >2 years with thalassemia major, sickle cell disease (SCD), low or intermediate (INT-1) risk MDS or other anemias, who are on, starting, or resuming treatment with deferasirox. The study began with a 1-month run-in phase with deferasirox dosed according to prescribing information, then a 3-month assessment phase where subjects could choose each week from 5 general administration options including with or without meals, in the morning or evening, crushed and added to a soft food, or mixed in a liquid of choice. Subject diaries are used to record the meal and method of administration at the end of each week. Palatability is assessed with a modified facial hedonic scale, with additional directed questions capturing gastrointestinal side effects. This is a data analysis of the run-in phase. Result: Target enrollment has been met with 65 patients. Baseline data on the first 58 subjects include 8 in the 2 to <10 years of age group (median 7.5 years; range 3–9); 42 in the 10 to <60 years of age group (median 18.5 years; range 10–48); and 8 in the ≥60 years of age group (median 74 years; range71-83). Underlying hematologic diagnoses included SCD (41%), thalassemia major (29%), MDS (12%) and other anemias (17%). Sixty-nine percent of subjects were receiving deferasirox prior to entering the study. The median baseline serum ferritin level was 2405 μ g/L (range 560–8660) and was distributed as shown in Table 1. The most frequent adverse events were diarrhea (19%) and nausea (9%) (Table 2), which were more common in MDS (P=0.23 and P<0.01, respectively). Conclusion: This ongoing trial (NCT00845871) is evaluating whether alternative modes of administration improve palatability and tolerability while maintaining safety. Preliminary data from the assessment phase (deferasirox taken with meals, different liquids, or crushed and added to food) will be presented at the meeting. Disclosures: Goldberg: Novartis Oncology: Consultancy, Honoraria, Research Funding, Speakers Bureau. Off Label Use: Exjade, iron chelation therapy, off-label method of administration. Giardina:Novartis: Research Funding. Parkhurst Cain:Novartis: Research Funding. Chirnomas:Novartis: Research Funding. Esposito:Novartis: Employment. Paley:Novartis: Employment. Vichinsky:Novartis: Consultancy, Research Funding, Speakers Bureau; Hemaquest: Consultancy, Membership on an entity's Board of Directors or advisory committees; Apotex: Consultancy, Research Funding.

scholarly journals A holistic approach to iron chelation therapy in transfusion‐dependent thalassemia patients with serum ferritin below 500 μg/L

2020 ◽  
Vol 95 (9) ◽  
Author(s):  
Natalia Scaramellini ◽  
Dario Consonni ◽  
Elena Cassinerio ◽  
Carola Arighi ◽  
Alessia Marcon ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Holistic Approach ◽  
Iron Chelation Therapy

Iron Overload and Haematopoiesis in MDS: Does Blood Transfusion Promote Progression to AML?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2685-2685 ◽  
Author(s):  
Lap Shu Alan Chan ◽  
Rena Buckstein ◽  
Marciano D. Reis ◽  
Alden Chesney ◽  
Adam Lam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Bone Marrow Cells ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Ferritin Concentration

Abstract Introduction: The biology of myelodysplastic syndrome (MDS) is poorly understood, and treatment options are limited. Thus, most MDS patients require chronic red blood cell transfusion, and many develop secondary iron overload. Although the pathophysiological consequences of iron overload to the heart, liver, and endocrine organs have been well characterized, its effects on haematopoiesis have not been studied. However, it has been observed that chelation therapy in iron-overloaded MDS patients may result in reduction of transfusion requirements, and recent studies have suggested a correlation between the use of iron chelation therapy and improvement in leukaemia-free survival in MDS. At the cellular level, iron toxicity is mediated in large part via the generation of reactive oxygen species (ROS). It has been shown in animal models that accumulation of ROS leads to senescence of haematopoietic stem cells, and that ROS cause DNA damage and promote the development of malignancy. These effects of ROS may be particularly important in MDS, in which haematopoiesis is already severely compromised and genetic instability is a striking feature. Hypothesis: We hypothesize that iron overload secondary to transfusion leads to increased levels of intracellular ROS in early haematopoeitic cells in MDS. The increase in intracellular ROS in MDS would be predicted to lead further impairment of haematopoiesis via stem cell exhaustion and while promoting accumulation of DNA damage by myelodysplastic stem cells and early progenitors, thus accelerating progression of MDS to acute leukaemia. Results: To test this hypothesis, we examined the relationship between transfusion-related iron overload and ROS content of CD34+ bone marrow cells in MDS. ROS content was measured in CD34+ cells by flow cytometry in bone marrow aspirates from 34 consecutive MDS patients (CMML=4, MDS/MPD=2, RA=4, RARS=3, RCMD=2, RAEB 1=6, RAEB 2=12, RAEB-t/AML=1). The patients represented a wide range of prior transfusion burden (0-&gt;300 units PRBC) and serum ferritin levels (11-&gt;10000 μg/L). ROS was strongly correlated with serum ferritin concentration for patients with iron overload (serum ferritin &gt;1000 μg/L; n=14, R=0.733, p&lt;0.005). The correlation between ROS and ferritin level was even stronger in the subset of patients with RAEB 1 or RAEB 2 and iron overload (n=11, R=0.838, p&lt;0.005). In contrast, no correlation between ROS and ferritin level was demonstrated for patients with serum ferritin &lt;1000 μg/L (n=20). Importantly, iron chelation therapy was associated with a reduction in CD34+ cell ROS content in one patient. To assess the effect of iron overload on normal stem cell and progenitor function, we established a mouse model of subacute bone marrow iron overload. B6D2F1 mice were loaded with iron dextran by intraperitoneal injection (150mg total iron load over 21 days), and sacrificed three days after the end of iron loading. Iron staining of tissue sections confirmed iron deposition in the bone marrow, liver, and myocardium. The development of splenomegaly was noted in iron-loaded animals. Flow cytometric analysis revealed increased apoptosis of bone marrow cells in iron loaded mice based on annexin V+/7 AAD-staining (6.26±0.96% versus 3.54±0.99% for control mice, paired student’s t-Test p&lt;0.005). However, ROS content in CD117+ progenitors of iron loaded mice was similar to control mice. Thus, subacute iron loading in mice increases apoptosis but does not alter the ROS content of HSCs; we postulate that chronic iron overload is required to achieve this effect. Conclusions: These results establish a relationship between CD34+ cell ROS content and serum ferritin concentration in MDS patients with iron overload, and indicate that iron chelation therapy in this patient population reverses this ROS accumulation. The physiological consequences of this relationship are currently being investigated in this patient set by haematopoietic colony assays and assessment of DNA damage in CD34+ cells. Nonethelesss, these data may have key implications for the deployment of iron chelation therapy in MDS patients, and may explain the association between the use of iron chelation and improved leukaemia-free survival in MDS.

Deferasirox Safety Profile in Patients with Transfusion-Dependent Anaemias:Results From the Interim Analysis of a Hellenic Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3183-3183
Author(s):  
Vassilis Ladis ◽  
Marouso Drossou ◽  
Dimitria Vini ◽  
Ersi Voskaridou ◽  
Miranda Athanasiou-Metaxa ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Safety Profile ◽  
Interim Analysis ◽  
Pediatric Patients ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Liver Iron ◽  
Liver Iron Overload

Abstract Abstract 3183 Background: The introduction of iron chelation treatment has led to a significant improvement in morbidity and overall survival in patients with transfusion-dependent anemias. Deferasirox is a once-daily, oral iron chelator approved for the treatment of transfusional iron overload in both adult and pediatric patients. The efficacy and safety of deferasirox in a variety of transfusion-dependent anemias has been established in numerous Phase II/III clinical trials. Since most patients with transfusion-dependent anemias require lifelong iron chelation therapy, there is a need to assess the long-term safety of deferasirox in both adult and pediatric patients. Aim: To assess the safety profile of deferasirox in patients with transfusional iron overload in a real-world clinical setting. To further investigate the safety profile of deferasirox in patients with congenital erythrocyte disorders and transfusional iron overload, with ferritin levels <4000 ng/ml and without severe cardiac siderosis. Methods: Between July 2009 and September 2010, 85 patients with transfusion-induced iron overload treated with deferasirox as per the approved product labeling were enrolled in the study. These data represent the 24-week planned interim analysis of a 12-month observational study on deferasirox safety profile in the treatment of pediatric and adult patients with transfusion-dependent anemias who were newly-treated with deferasirox. Safety was evaluated through the monitoring and recording of all adverse events and serious adverse events, as well as routine laboratory testing, including hematology, blood chemistry and hepatic function assessments. Results: The population had a median age of 37.6 years (range: 5.3–61.4) and a female to male ratio of 1.3. Beta-thalassemia (67.1%) was the most common transfusion-dependent anemia, followed by thalassemia intermedia requiring periodic transfusions (20.0%) and sickle cell anemia (12.9%). Mean baseline ferritin levels were 1502.1±870.5 (pediatric group: 1480.2±522.8 and adult group: 1503.6±891.4), while 53 out of the 85 patients (62.4%) had serum ferritin level above 1000 ng/ml. Mean baseline liver T2* value was 10.4±9.7 ms; 44.4% of patients demonstrated minimal liver iron deposition (MRI T2* > 6.3 ms), 51.4% had mild to moderate liver iron overload (T2* ≤ 6.3 ms), and 4.2% had severe liver iron overload (T2*<1.4 ms). 54 (63.5%) of patients analysed had been pre-treated with iron chelators and 31 (36.5%) were chelation-naïve. The initial average daily dose of deferasirox was 25.9±4.8 mg/kg, and 70.6% of patients had no dose modification during the 24-week follow-up period. A statistical significant decrease in median serum ferritin levels was observed by Week 24 (mean absolute change from baseline:-214.5 ng/mL; p=0.009) [Figure 1]. No statistically significant changes were observed in creatitine levels, creatinine clearance and transaminases by Week 24 [Figure 1]. 37 ADRs were reported by 17 patients (20%) over the 24-week period. Among the most frequently observed ADRs (>5%) were epigastralgia reported by 7.1% of patients (6/85) and loose stools/diarrhoea by 5.9% of patients (5/85). The majority of ADRs reported (nevents=25; 67.6%) were graded as mild in severity, while 21.6% (nevents=8) were graded as moderate and 10.8% (nevents=4) as severe. Most ADRs (nevents=31; 83.8%) resulted in full recovery by Week 24. The overall incidence of SADRs was as low as 1.2% (in particular one patient experienced severe epigastralgia and upper extremity pain which resulted in her withdrawal from the study after four months of treatment). The all-cause discontinuation rate was 9.4% (8/85), while only two patients (2.4%) discontinued the study therapy due to ADR; 1 patient due to increased transaminase levels and 1 patient due to the aforementioned SADR. Conclusions: These data highlight the safety profile of deferasirox in both adult and pediatric patients; the regular monitoring of serum ferritin levels as well as other iron-overload parameters and transfusion requirements play a major role in determining and optimizing the outcome of iron chelation therapy. Disclosures: Ladis: Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Drossou:Novartis Pharmaceuticals: Investigator participating in a trial sponsored by Novartis. Vini:Novartis Pharmaceuticals: Investigator participating in a trial sponsored by Novartis. Athanasiou-Metaxa:Novartis Hellas S.A.C.I.: Research Funding. Oikonomou:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Vlachaki:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Tigka:Novartis Hellas S.A.C.I.: Employment. Tzavelas:Novartis Hellas S.A.C.I.: Employment. Liakopoulou:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Adamopoulos:Novartis Hellas S.A.C.I.: Investigator participating in a trial sponsored by Novartis. Kattamis:Novartis Hellas S.A.C.I.: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Are Children with Cancer Receiving Myelosuppressive Therapy At Risk for Transfusion-Related Iron Overload?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1180-1180
Author(s):  
Anushka Jaffer ◽  
Rebecca Barty ◽  
Erin Jamula ◽  
Grace Wang ◽  
Yang Liu ◽  
...  
Keyword(s):  
At Risk ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Children With Cancer ◽  
Screening Practices ◽  
The Impact ◽  
Rbc Transfusion

Abstract Abstract 1180 Background Transfusion-related iron overload (TRIO) is associated with significant morbidity and mortality. Adequate screening for iron overload (IO) and the use of iron chelators, if needed, should be employed for chronically transfused individuals. However, with the exception of patients with hemoglobinopathies, screening for iron overload is not a consistent part of routine care for patients receiving multiple red cell transfusions, and is not identified as a treatable problem. Objective This study aimed to identify the population at risk for TRIO and to evaluate current screening practices. Methods All children (≤ 18 years) receiving at least one red blood cell (RBC) transfusion between January 1, 2008 and December 31, 2011 at our institution were identified using the TRUST (Transfusion Registry for Utilization, Surveillance and Tracking) database. Only patients receiving chronic RBC transfusion were included in this study, which was defined as receiving ≥20 units of RBC or ≥ 20 RBC transfusions dosed at 15ml/kg within 12 consecutive months where the transfusions were not administered in the setting of an operating room, trauma or surgical procedure(s), not administered 7 days prior/post-surgical procedures and not all administered within one day. Adjudication by a second reviewer resolved any ambiguity regarding study inclusion. Medical records of eligible patients were reviewed to collect patient demographics, underlying diagnosis and reason for transfusions, and to evaluate IO screening practices (e.g. ferritin level, testing for systemic IO (e.g. FerriScan) if persistently high ferritin) and frequency of iron chelation therapy. Results A total of 35 patients fulfilled the eligibility criteria, with a mean age of 8.82 years (SD 5.36). Table 1 summarizes the demographics of the population, the transfusion requirements, how often the patient subgroups were screened and the screening results. In summary, 20 patients had ferritin levels checked, where 2 (AML and hepatoblastoma) patients had values under 500 μg and no screening was required. Of the remaining 18, 10 patients were diagnosed with a hemoglobinopathy (8) and congenital anemia (2) requiring chronic transfusions and underwent regular screening for iron overload and received iron chelation therapy. The remaining 8 patients had ferritin level >500 μg but no IO screening ordered. Of these 8 patients the majority were diagnosed with a cancer (leukemia, solid tumours) (5), acquired aplastic anemia (2), and hemophagocytic syndrome (1). The total number of transfusions for these 8 patients ranged from 20 to 52 with a median of 25 transfusions. Conclusion The majority (63%) of chronically transfused patients in this cohort had underlying cancer requiring aggressive chemotherapy. Only 32% of these patients had ferritin level tested and none were evaluated for systemic IO. TRIO may represent an additional, as yet unidentified, co-morbidity of cancer therapy. Therapies such as anthracycline or radiation may potentiate the end organ effect of TRIO at levels lower than that observed in patients with a hemoglobinopathy. Hence, it is important to develop strategies to evaluate children with cancer at risk for IO and to study the impact of transfusional iron accumulation on end organ function. Disclosures: No relevant conflicts of interest to declare.

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