Median Serum Ferritin Level Research Articles

Iron chelation therapy with deferasirox in the management of iron overload in primary myelofibrosis.

Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.

Efficacy of deferasirox in children with β‐thalassemia: Single‐center 3 year experience

Iron chelation therapy is an important component in the management of patients with β-thalassemia. The study included 87 children with transfusion-dependent β-thalassemia aged 2-17 years (mean, 8.2 ± 4.1 years), 49 (56%) of whom were male. The patients received deferasirox 9-40 mg/kg per day as a single dose for 36 months. They were clinically and laboratory monitored. The treatment was generally well tolerated. Drug-related adverse events, including abdominal pain (14.9%) and nausea (5.8%), high alanine aminotransferase more than double the upper limit of normal (5.8%), and non-progressive rise in serum creatinine (2.3%), were generally mild to moderate, transient, and reduced in frequency over time. Two patients discontinued treatment due to severe abdominal pain and nausea. Mean deferasirox dose was calculated as 21.2 ± 8.6, 23.7 ± 8.1, 30.7 ± 8.2 and 32.4 ± 7.6 mg/kg per day at 0, 12, 24 and 36 months, respectively. Mean (median) serum ferritin level was found to increase progressively during the first 22 months of treatment, from 3.161 ± 1.683 ng/mL (2.760 ng/mL) to 3.679 ± 1.997 ng/mL (3.071 ng/mL; P < 0.001) and then decreased gradually to 2.907 ± 1.436 ng/mL (2.670 ng/mL; P = 0.023) at 36 months. Deferasirox is safe and well tolerated; doses 21-24 mg/kg per day were not able to maintain stable iron balance, but ≥ 30 mg/kg per day was able to reduce iron in regularly transfused pediatric patients.

Deferasirox for transfusion‐dependent patients with myelodysplastic syndromes: safety, efficacy, and beyond (GIMEMA MDS0306 Trial)

In the absence of randomized, controlled trial data to support iron chelation therapy in transfusion-dependent patients with myelodysplastic syndromes (MDS), continued evidence from large prospective clinical trials evaluating the efficacy and safety of iron chelation therapy in this patient population is warranted. The safety and efficacy of deferasirox was examined in a prospective, open-label, single-arm, multicenter trial of transfusion-dependent patients with International Prognostic Scoring System low- or intermediate-1-risk MDS and evidence of transfusion-related iron overload. The effects of deferasirox therapy on hematological response and disease progression were also examined. Of 159 participants enrolled from 37 Italian centers, 152 received ≥1 dose of deferasirox (initiated at 10-20mg/kg/day and titrated as appropriate), and 68 completed the study. Of 84 patients who discontinued deferasirox therapy, 22 died during the trial, and 28 withdrew due to an adverse event (AE). Fourteen treatment-related grade 3 AEs occurred in 11 patients, whereas no grade 4 or 5 drug-related AEs were reported. Significant risks for dropout were a higher serum ferritin level at baseline, a higher MDS-Specific Comorbidity Index, and a shorter diagnosis-enrollment interval. Median serum ferritin level fell from 1966ng/mL to 1475ng/mL (P<0.0001). The cumulative incidence of transfusion independence, adjusted for death and disease progression, was 2.6%, 12.3%, and 15.5% after 6, 9, and 12months, respectively. Deferasirox therapy in transfusion-dependent patients with MDS was moderately well tolerated and effectively lowered serum ferritin levels. Positive hematological responses were observed, and a subset of patients achieved transfusion independence.

How Early Can Myocardial Iron Overload Occur in Beta Thalassemia Major?

BackgroundMyocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM.Methods and ResultsWe analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload.ConclusionsThe TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old.

How does the quality of life and the underlying biochemical indicators correlate with the performance in academic examinations in a group of medical students of Sri Lanka?

BackgroundIndividual variation of examination performance depends on many modifiable and non-modifiable factors, including pre-examination anxiety. Medical students’ quality of life (QoL) and certain biochemical changes occurring while they are preparing for examinations has not been explored.PurposeWe hypothesize that these parameters would determine the examination performance among medical students.MethodsFourth-year medical students (n=78) from the University of Ruhuna, Sri Lanka, were invited. Their pre- and post-exam status of QoL, using the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire, and the level of biochemical marker levels (i.e., serum levels of thyroid profile including thyroglobulin, cortisol and ferritin) were assessed. Differences between the scores of QoL and serum parameters were compared with their performance at the examination.ResultsThe mean QoL score was significantly lower at pre-exam (56.19±8.1) when compared with post-exam (61.7±7.1) levels (p<0.001). The median serum TSH level prior to the exam (0.9 mIU/L; interquartile range 0.74–1.4 mIU/L) was significantly lower (p=0.001) when compared with the level after the exam (median of 2.7 mIU/L; IQR 1.90–3.60). The mean±SD fT4 level was significantly higher before the exam (19.48±0.4 pmol/L at study entry vs. 17.43±0.3 pmol/L after the exam; p<0.001). Median serum ferritin (SF) level prior to the exam (43.15 (23.5–63.3) µg/L) was significantly lower (p≤0.001) when compared with after-exam status (72.36 (49.9–94.9) µg/L). However, there was no difference in mean serum cortisol levels (16.51±0.7 at pre-exam and 15.88±0.7 at post-exam, respectively; p=0.41).ConclusionsStudents had higher fT4 and low ferritin levels on pre-exam biochemical assessment. It was evident that students who perform better at the examination had significantly higher QoL scores at each domain tested through the questionnaire (Physical health, Psychological, Social interaction and Environment). The higher the QoL scores, the better the grades were. It was also found that students who failed exhibited profound differences in the QoL score.

Significant Impact Of Iron Chelation After Allogeneic Hematopoetic Stem Cell Transplantation On Disease Recurrence: Potential Anti-Leukemic Activity

▪Iron overload (IO), primarily related to multiple red blood cell transfusions, is a relatively common complication in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Elevated pre-transplant ferritin level, a surrogate marker of iron overload, was demonstrated to be an important cause of mortality and morbidity in patients who have undergone allo-HSCT. Excessive iron accumulation results in tissue damage and organ failure, mainly as a result of the generation of free radicals that cause oxidative damage and organ dysfunction. Iron chelators have been widely used leading to normalisation for ferritine level and lower IO-related complications. As iron has a fundamental role in cell survival affecting pathways involved in DNA synthesis, cell differentiation, and apoptosis, some studies evaluated the anti-proliferative activity of iron chelators in cancer and leukemia patients on disease recurrence. The objective of this study was to determine at a first time the impact of serum ferritin level measured at time of allogeneic HSCT in adult patients with hematological disorders on the different outcomes and to investigate at a second time the role of iron chelation on relapse incidence. We included 158 patients, 100 males and 58 females with a median age of 45 years (18-67) who underwent allo-HSCT between 2002 and 2010. There were 83 acute myeloid leukemias, 10 chronic myeloid leukemias, 11 myelodysplastic syndromes, 7 myeloproliferative disorders, 19 myelomas, 9 non-Hodgkin lymphomas, 6 Hodgkin diseases, 5 aplastic anemias and 3 hemoglobinopathies. Sixty-seven (42%) patients were sex mismatched (F→M:37; M→F:30); for ABO compatibility, 61% were compatible, 18% had minor incompatibility and 21% had major incompatibility. Concerning the HSCT procedures, 60 patients (38%) received peripheral blood stem cell and 98 (62%) received bone marrow from 97 (61%) HLA related donors [matched, n=76; mismatched, n=21], and 61 (39%) HLA unrelated donors [matched, n=36; mismatched, n=25] after myeloablative [n=64, (41%)] or reduced intensity conditioning [n=94, (59%)]. At transplantation, 91 (58%) were in complete remission (CR) or chronic phase [CR1: n=61 (67%); ≥CR2: n=30 (33%)]. The median serum ferritin level at HSCT was 1327 microg./l (26-14136); 31(20%) patients had a level 26-500, 33 (21%) had a level 500-2500, and 94 (59%) >2500. There was no significant correlation between the different ferritin levels, disease kind and status at HSCT. After transplantation, 23 patients received iron chelating agents after a serum ferritin level of 1000 microg/l and stopped when the level decreased below 1000. The cumulative incidence of acute GVHD ≥ II at 3 months was 14% (11-16.5) with 10.5% (8-13) for grade III and 7% (5-9) for grade IV; the 1 year cumulative incidence of limited and extensive chronic GVHD were 4% (2-6) and 12.4% (9-16) respectively. After a median follow-up of 18 months (1-106), the 5 years OS probability was 65% for patients with ferritin level below 500 microg./l, 39% for level between 500 and 2500 microg./l and 28% for level > 2500 micog./l, [Hazard ratio= 3.5 (1.5-8.1), p=0.002]; this was explained by a significant higher TRM in patients with level >2500 [Hazard ratio= 4.3 (1.02-18), p=0.04]. Interestingly, we found in multivariate analysis that patients receiving iron chelators had significantly better OS [5 years OS= 59% vs. 34% for non-chelated patients, Hazard ratio= 0.34 (0.15-0.76), p=0.008], (Figure 1a), and experienced less disease relapse [5 years relapse incidence= 18% vs. 41% for non-chelated patients, Hazard ratio= 0.22 (0.07-0.73), p=0.012], (Figure 1b). In conclusion, we confirmed the negative impact of iron overload on the outcomes allo-HSCT recipients. More importantly, we demonstrated that iron chelators have a positive impact in reducing disease relapse by the possible mechanism of iron deprivation in leukemic cells. This clinical observation needs to be confirmed by prospective randomized trials. [Display omitted] Disclosures:Michallet:Novartis: Honoraria, Research Funding. Nicolini:Novartis: Consultancy, Honoraria, Research Funding.

Serum Ferritin Level As a Prognostic Marker For Peripheral T-Cell Lymphoma.

BackgroundPeripheral T-cell lymphoma (PTCL) is known to have an aggressive clinical course and be associated with poor survival. The International Prognostic Index (IPI) score and the Prognostic Index for T-cell lymphoma (PIT) have been suggested as methods to predict the prognosis of PTCL. Ferritin, the iron storage protein, is associated with chronic inflammation. Although higher levels of serum ferritin are detected in many cancer patients, the significance of elevated serum ferritin as a prognostic factor for lymphoma has yet to be established. Thus, our retrospective study aimed to examine the prognostic value of serum ferritin levels in PTCL. Patients and MethodsSerum ferritin levels were evaluated in 78 patients with PTCL, who were treated with anthracycline-containing regimens in 8 institutions affiliated to the Yokohama City University Hematology Group between 1998 and 2011. Fourteen patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); 44 receivedpirarubicin, cyclophosphamide, vincristine, and prednisone (THP-COP); 3 received THP-COP followed by radiotherapy; 3 received up-front autologous peripheral blood stem cell transplantation; and 14 received THP-COP at 2-week intervals in a clinical trial. ResultsThe study population comprised 50 male and 28 female patients with a median age of 64 years at the time of diagnosis (range, 16–83 years). With regard to the PTCL subtype, 39 patients had PTCL, not otherwise specified, and 39 had angioimmunoblastic T-cell lymphoma. Twelve patients had localized disease and 66 patients had advanced Ann Arbor stage lymphoma. Twenty-three patients had a poor Eastern Cooperative Oncology Group performance status (PS) of 2–4. B symptoms were present in 34 patients. Risk stratification according to the IPI was as follows: low risk, 9 patients; low–intermediate risk, 20 patients; high–intermediate (HI) risk, 30 patients; and high (H) risk, 19 patients. According to the PIT, 4 patients were categorized into group 1, 25 into, group 2 , 28 into, group 3, 21 into, as group 4. The median observation period for the surviving patients was 50 months. The median serum ferritin level was 183 ng/ml (range, 5–14,622 ng/ml). Factors associated with a poor overall survival (OS) in univariate analysis were HI and H risk status with regard to IPI (P = 0.024), assignment to group 3 or 4 with regard to PIT (P = 0.017), poor performance status (P< 0.001), and ferritin levels ≥ 300 ng/ml (P< 0.001). The 4-year OS rate of all 78 patients was 54%. The 4-year OS rate was poorer in patients with serum ferritin levels ≥300 ng/ml (n = 21) than in those with serum ferritin levels< 300ng/ml (n = 57; 22% vs. 65%; P< 0.001) (Figure). Multivariate analysis including each factor comprising the IPI (age, lactate dehydrogenase level, PS, Ann Arbor stage, and number of extranodal lesions), gender, bone marrow involvement, and serum ferritin level showed that poor PS (P = 0.002, relative risk [RR] 3.6) and a serum ferritin level ≥300 ng/ml (P = 0.014, RR 2.7) were independent risk factors for poor OS. [Display omitted] ConclusionThe serum ferritin level is a useful prognostic marker for PTCL. Disclosures:No relevant conflicts of interest to declare.

Natural Course Of Serum Ferritin In Childhood Cancer Survivors: Need For Iron Removal Therapy?

BackgroundIron overload has been reported in adult survivors of leukemia after chemotherapy with or without allogeneic hematopoietic stem cell transplantation (allo-HSCT). Approximately 10-15% of adult survivors suffer from liver dysfunction, endocrine disorders, and/or cardiac dysfunction due to iron overload, in which free radicals produced by iron could damage tissues. Therefore phlebotomy and iron chelation therapy in adult survivors have been used prophylactically, however iron overload has not been studied extensively in childhood survivors, so that it would be a problem how to manage the childhood patients in whom serum ferritin level was high at the completion of chemotherapy. In this study, we retrospectively analyzed the serum ferritin level over time after the completion of therapy and also referred to whether iron chelation therapy and/or phlebotomy would be needed or not in childhood survivors. Patients and methodsWe retrospectively analyzed the level of serum ferritin overtime in 48 childhood cancer survivors (ALL 19, AML 13, Lymphoma 5, Pediatric solid tumor 11) except allo-HSCT, who were transfused concentrated red cells in our hospital. All the patients did not receive any phlebotomy and iron chelation therapy throughout the course. ResultsThe total mean concentrated blood transfusion volume was 114 ml/kg (114±16, ranges 7-672). At the completion of chemotherapy, the median serum ferritin level was 867 ng/ml (867±216, ranges 7-6558). Three years after chemotherapy, the median serum ferritin levels decreased to 281 ng/ml (281±77, ranges 7-1285). All patients did not show any symptoms related to iron overload such as liver dysfunction and glucose intolerance. Twelve out of 48 patients (25%) exceeded 1000 ng/ml of the serum ferritin at the time of completion of chemotherapy, which has been considered as the initiation of iron chelation therapy in adult patients. However all patients except one decreased the serum ferritin level below 1000 ng/ml in 3 years after chemotherapy without any iron removal therapy. Although serum ferritin level in the exceptional case was extraordinary high (6558 ng/ml) compared to other cases at the completion of chemotherapy, it declined to 1285 ng/ml spontaneously in 3 years, which was much better than expected. ConclusionsAlthough 25 percent of our childhood cancer survivors showed high level of serum ferritin more than 1000 ng/ml at the time of completion of chemotherapy, almost all the cases eventually declined thereafter without any iron removal therapy probably due to the iron consumption with growth. Further study would be needed to make specialized criteria for initiating iron removal therapy for childhood cancer survivors. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Multiple Packed Red Blood Cell (PRBC) Transfusions In Pediatric Patients With Acute Myeloid Leukemia (AML) Result In a Large Transfusional Iron Dose With The Potential For Long-Term Organ Dysfunction

▪The treatment of AML in children utilizes intensive chemotherapy and often myeloablative hematopoietic cell transplant (HCT). This results in significant myelosuppression, necessitating blood product transfusions. Repeated PRBC transfusions result in an increase in the body iron load which can lead to secondary hemochromatosis and organ dysfunction, particularly the heart and liver. Patients with hemoglobinopathies on chronic PRBC transfusions require iron chelation therapy usually after 10-20 units transfused. While patients with AML receive multiple transfusions, there is little data on the number or volume of PRBC transfused or the estimate of the iron load received.This retrospective study evaluated the number and volumes of PRBC transfusions administered to pediatric (<14 years) patients with AML, and calculated an estimate of the iron infused.Twenty-two patients with AML were diagnosed and treated at our institution between January 2010 and December 2012. There were 13 girls and 9 boys with a median age at diagnosis of 7.5 years (mean 6.95; range 0.4-13.2). One patient died early of sepsis without achieving complete remission (CR), and another died in CR following her last course of chemotherapy. Eight patients underwent HCT following myeloablative conditioning with busulfan, cyclophosphamide and etoposide; the remaining received chemotherapy alone. For patients who completed their chemotherapy the cumulative anthracycline dose was 450 mg/m2. Patients received a median of 17.5 PRBC transfusions (mean 16.6; range 3-28) during the course of their treatment. The cumulative PRBC transfusion volume was 185.4 ml/kg (mean 175.8; range 24.87 – 311.58), which translates to a median iron dose of 129.8 mg/kg (mean 123.1; range 17.4 – 218.1). The median serum ferritin level for those patients who were tested (n=12) was 1794.5 mg/L (mean 9074.5; range 699 – 78500). The median projected hepatic iron content, based on the transfused iron burden was 12.24 mg/g liver dry weight (mean 11.61; range 1.64 – 20.58); 17 (77.3%) patients had projected hepatic iron concentrations in excess of 7.0 mg/g, and none were <1.6 mg/g. Ten patients have developed a > 10 percentage point reduction in their left ventricular ejection fraction (LVEF; range -11% to -45%) however only one patient is on cardiac failure medications. Cardiac T2* MRI studies are being conducted to evaluate cardiac iron status for patients in this cohort. 13 patients were alive in CR at a median follow-up duration of 1.83 years (mean 2.16; range 0.27 – 3.43).Pediatric patients with AML receive large volumes of PRBC transfusions during their treatment and as a consequence accumulate high total body iron. This is in excess of the threshold for chelation therapy, used to prevent organ dysfunction, in patients with hemoglobinopathies. In addition, AML patient also receive significant cardio-toxic medications which may compound the effect of iron on the myocardium. With improvements in long term survival for patients with AML the addition of iron chelation therapy must be studied in order to prevent long term toxicity of AML therapy. Disclosures:No relevant conflicts of interest to declare.

Cardiac iron overload assessed by T2* magnetic resonance imaging and cardiac function in regularly transfused myelodysplastic syndrome patients

Cardiac iron overload assessed by <scp>T</scp>2* magnetic resonance imaging and cardiac function in regularly transfused myelodysplastic syndrome patients

Impact of Hyperferritinemia on the Outcome of Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Lymphoid Malignancies

Hyperferritinemia has been associated with adverse outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning. However, its characteristics and impact on the outcome in the reduced-intensity conditioning (RIC) and in the lymphoid malignancy settings are far from clear. The study includes 201 adult patients undergoing allo-HCT with RIC (allo-RIC) for lymphoid malignancies with a median follow-up for survivors of 52 months (range, 3 to 123). Median serum ferritin level at allo-RIC was 379 ng/mL (range, 4 to 10,790). In the multivariate analysis, patients with hyperferritinemia at transplantation (>399 ng/mL) showed lower 4-year overall survival (hazard ratio [HR], 1.8 [95% confidence interval {CI}, 1.2 to 2.8]; P = .008), higher nonrelapse mortality (NRM) (HR, 1.8 [95% CI, 1.1 to 3.2]; P = .03), and higher infection-related mortality (HR, 2.3 [95% CI, 1.1 to 4.8]; P = .02) than patients without hyperferritinemia. Neutrophil and platelet engraftment and 100-day NRM were similar between both groups. The adverse outcome associated with hyperferritinemia seemed higher in patients without major comorbidities and was not influenced by the elevation of acute phase reactants. Our results indicate that high ferritin levels at HCT are associated with an adverse outcome after allo-RIC in patients with lymphoid malignancies.

Diagnostic Use of Serum Ferritin Levels to Differentiate Infectious and Noninfectious Diseases in Patients with Fever of Unknown Origin

INTRODUCTION: In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases.METHODS: FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed.RESULTS: Of the 77 patients, 11 were caused by infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0–951.8) ng/mL for the infectious disease group, 1818.2 (485.4–4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6–1927.2) ng/mL for the noninfectious inflammatory disease group,p= 0.048, Kruskal–Wallis test). By comparison using the Mann–Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p= 0.049) and between the infectious disease and groups (p= 0.04).CONCLUSION: An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL.

Diagnostic use of serum ferritin levels to differentiate infectious and noninfectious diseases in patients with fever of unknown origin.

INTRODUCTION: In this study, we determined whether serum ferritin levels could be used to differentiate between fever of unknown origin (FUO) caused by infectious and noninfectious diseases.METHODS: FUO patients were hospitalized at Chonnam National University Hospital between January, 2005 and December, 2011. According to the final diagnoses, five causes were identified, including infectious diseases, hematologic diseases, noninfectious inflammatory diseases, miscellaneous and undiagnosed.RESULTS: Of the 77 patients, 11 were caused by infectious diseases, 13 by hematologic diseases, 20 by noninfectious inflammatory diseases, 8 by miscellaneous diseases, and 25 were undiagnosed. The median serum ferritin levels in infectious diseases was lower than those in hematologic diseases and (median (interquartile range) of 282.4 (149.0–951.8) ng/mL for the infectious disease group, 1818.2 (485.4–4789.5) ng/mL for the hematologic disease group, and 563.7 (399.6–1927.2) ng/mL for the noninfectious inflammatory disease group, p = 0.048, Kruskal–Wallis test). By comparison using the Mann–Whitney test, statistically significant differences were found only between the infectious disease and hematologic disease groups (p = 0.049) and between the infectious disease and groups (p = 0.04).CONCLUSION: An optimal cutoff value of serum ferritin levels to predict FUO caused by a noninfectious disease (hematologic diseases, noninfectious inflammatory diseases) was established as 561 ng/mL.

Correlation between serum ferritin levels and attention-deficit/hyperactivity disorder symptom scores in children based on the Abbreviated Conners Teachers Rating Scale

factors causing attention􀁚defidt /hyperactivity disorder (ADHD)in children. Iron contributes to the regulation of dopamineneurotransmitter activity, thus, iron deficiency has been associatedwith ADHD. Several studies have been conducted in othercountries to assess for a correlation between serum ferritin levelsand ADHD symptom scores, but 'With varied results.Objective To examine the relationship between iron deficiency andADHD symptoms, in particular the correlation between serumferritin levels and Abbreviated Conners Teachers Rating Scale(ACTRS) scores in children v.ith ADHD.Methods T his cross􀁚sectional study was performed in childrenaged 5􀁚 12 years who were newly diagnosed \\lith ADHD. Subjectswere recruited from the Klinik Anakku Kelapa Gading, theNeurology Outpatient Clinic, the Growth and Development􀁚Social Pediatrics Outpatient Clinic, and the Integrated ChildClinic of Cipto Mangunkusumo Hospital. ADHD diagnoses wereestablished using Diagnostic and Statistical Manual of MentalDisorders, 4th edition (DSM􀁚IV). Subjects' parents and teacherswere asked to complete the ACTRS instrument sheet. Venousblood specimens were obtained for peripheral blood and serumferritin level tests.Results Of the 33 subjects recruited, 23 were male. Subjects' agesranged from 5􀁚 12 years, \\lith a median age of onset of 4 (range2􀁚 10) years. The combined type of ADHD (with inattention andhyperactivity􀁚impulsivity) was more commonly found (20/33)in our subjects. T he mean serum ferritin was 51.31 (SD 27.7)ng/mL. Using 20 ng/mL as the serum ferritin cutoff value, 5/33subjects were considered to be iron deficient. Median ACTRSscore by parents and teachers were 15 and 15, respectively. Higherscores were found in the combined type subject group than in theinattention type subject group. Median serum ferritin levels ofthe two ADHD type groups were similar. Median ACTRS scoresof parents and teachers tended to be higher in the iron􀁚deficientgroup (16 and 16, respectively) than in the normal serum irongroup (14.5 and 12.5, respectively). Serum ferritin level showedno correlation (r=􀁚0.243; P=0.086) to the parents' ACTRSscore, and no correlation (r=􀁚.057; P=0.377) to the teachers'ACTRS score.Conclusion Serum ferritin level showed no correlation to ACTRSscores of parents and teachers, respectively. However, the medianACTRS score was higher in the iron􀁚deficiency group than in thenormal iron status group, suggesting that there may be a qualitativerelationship between iron deficiency and ADHD symptoms.[Paediatr lndanes. 2012;52:329-35].

Association Between Increased Liver Iron Concentration and Vitamin D Deficiency in Patients with Transfusion Dependent Hemoglobinopathies in British Columbia

Abstract 3203 Background:Patients with transfusion dependent (TD) hemoglobinopathies are at risk of endocrinopathies and bone disease due to iron overload (IOL). Vitamin D is involved in regulation of calcium homeostasis, bone health and other clinical endpoints. Vitamin D deficiency is a common manifestation of patients with transfusional IOL; the mechanism remains unclear. Vitamin D hydroxylation occurs in the liver; whether liver IOL interferes with this step has not to date been addressed. This study investigates an association between liver iron concentration (LIC) and vitamin D levels in patients with TD hemoglobinopathies. Methods:Patients with TD b thalassemia major (TM), hemoglobin Eb TM (Eβ TM), and congenital dyserythropoetic anaemia (CDA) attending the Inherited Bleeding and Red Blood Cell Disorder Program at the adult (St. Paul’s Hospital) or pediatric (BC Children’s Hospital) programs in Vancouver, Canada were included if they had an assessment of LIC done by magnetic resonance imaging (MRI) and 25-hydroxyvitamin D3 (25 OH D3) levels between January 2009 and the 31st of December 2011. The analysis was restricted to patients >16 years of age to minimize confounding due to body mass. Clinical data collected included: gender, ethnicity, type of iron chelation therapy (ICT) and vitamin D and calcium supplementation. Laboratory data included: serum ferritin level, 25 OH D3, phosphorus (PO4), ionized calcium (Ca2+), parathyroid hormone (PTH) and thyroid stimulating hormone (TSH). Vitamin D insufficiency was: 25 OH D3 level <75 nmol/L and deficiency <60 nmol/L. Liver and cardiac iron assessment was done by T2* or R2* MRI. Liver iron was: LIC <2 mg/gmDW, normal; 2–5 mg/gmDW, mild; 5.1–7 mg/gmDW, moderate; >7 mg/gmDW severe. Cardiac IOL was: >20 ms, normal; 14–20 ms, mild; 8–15 ms, moderate; <8 ms, severe. Bone mineral density (BMD) was assessed by dual emission X-ray absorptiometry (DEXA) scans of the hip. BMD was: Z score <−1.5, osteopenia; and <−2.0, osteoperosis. Associations between variables were assessed using the Chi-square or Fischer’s exact test and the Pearson correlation. Results:26 patients with TD: βTM, n=21; Eβ TM, n=3; and CDA, n=2 were included, 21 adults and 5 from the pediatric program. Patients characteristics were: median age 24 (range 16–51) years and 11 (42.3%) were male. Ethnicities were: Asian, 11 (42.3%); Indian, 6 (23%); unclear ethnicity, 5 (19.2%); Middle Eastern, 3 (11.5%); and Caucasian, 1 (3.8%). The mean amount of blood received annually was 9633.9 (4677–14,508) mls/year. All patients were receiving ICT: deferasirox (DFX), 16 (61.5%); desferrioxamine (DFO), 8 (30.8%); and combination DFX+DFO, 2 (7.7%). 15 (57.7%) patients received vitamin D and calcium supplementation in variable doses and formulations. Median 25 OH D3 was 66.5 (18–125) nmol/L and vitamin D deficiency/insufficiency occurred in 15 (57.7%) patients: <75 nmol/L, n=15; and <60 nmol/L, n=10. Median Ca2+ was 2.37 (2.2–2.52) mmol/L, PO4 1.21 (0.78–1.71) mmol/L, AST 24.5 (16–46) U/L and ALT 18 (range10–50) U/L; all within normal. Median serum ferritin level was 693.5 (223–3553) mcg/L, LIC 4.25 (1.1–31.8) mg/g dry weight (DW) and median cardiac iron concentration was 35 (13–53.9) ms. Median BMD at the hip was −1.25 (−0.2–−3.7). There was a significant association between LIC >5 mg/gDW, and vitamin D level <60 nmol/L (P= 0.034), with 10 (38.5%) patients having an LIC ≥5 mg/gDW, 5 of whom had a vitamin D level <60 nmol/L. There was an inverse correlation between LIC and vitamin D level, with a Pearson coefficient of −0.33. There was no significant association between: vitamin D level and age, ethnicity, degree of transfusion requirement (DTR), ferritin level or type of ICT; or LIC and age, DTR, ferritin or BMD (P=NS for all). Conclusion:In this single center study of patients with transfusion dependent hemoglobinopathies, we found a significant association between LIC ≥5 mg/gDW and vitamin D level <60 nmol/L, with an inverse correlation between LIC and vitamin D level, suggesting that liver IOL may affect hepatic vitamin D metabolism and result in deficiency. These results warrant verification in larger numbers of patients and prospective trials and investigation of whether vitamin D insufficiency is linked to clinical endpoints. Patients may require intensification of vitamin D supplementation, and/or intensification of iron chelation therapy, particularly if a link to clinical consequences is demonstrated. Disclosures:Ezzat:Novartis: Honoraria. Leitch:Novartis: Honoraria, Speakers Bureau, participated in advisory boards Other.

Iron Overload in Patients with Hematological Disorders Undergoing Allogeneic HSCT: Unrevealed Implication in Different Outcomes

AbstractAbstract 4527The main objective of this study was to determine the impact of serum ferritin level on the different allogeneic HSCT outcomes in adult patients with hematological disorders in addition to other disease and patient variables. We evaluated the implication of iron overload in the HSCT mortality causes and the potential role of iron chelation. We included 158 patients, 100 males and 58 females with a median age of 45 years (18–67) who underwent allo-HSCT between 2002 and 2010. There were 83 AML, 10 CML (3CP, 2AP, 5BC), 11 MDS (10 acute phase; 1 CMML), 7 myeloproliferative disorders, 19 MM, 9 NHL, 6 HDG, 5 aplastic anemia and 3 hemoglobinopathies. Sixty-seven (42%) patients were sex mismatched (F→M:37; M→F:30); for ABO compatibility, 61% were compatible, 18% had minor incompatibility and 21% had major incompatibility. For CMV status, 36% were sero-negative, 15% were D+R-, 18% were D-R+ and 31% were D+R+. Concerning the HSCT procedures, 60 patients (38%) received PBSC and 98 (62%) received BM from 97 (61%) HLA related donors [matched, n=76; mismatched, n=21], and 61 (39%) HLA unrelated donors [matched, n=36; mismatched, n=25] after MAC [n=64, (41%)] or RIC [n=94, (59%)]. At transplantation, 91 (58%) were in CR or CP [CR1: n=61 (67%); ≥CR2: n=30 (33%)] and the rest of patients were in less that CR or CP [n=67 (42%)]. The median serum ferritin level at HSCT was 1327 microg./l (26–14136); 31(20%) patients had a level 26–500, 33 (21%) had a level 500–2500, and 94 (59%) >2500. There were no significant correlation between the different ferritin levels, disease kind and status at HSCT. Twenty two patients received iron chelating agents (Exjade, n=19; Desferal, n=3). After allo-HSCT, the cumulative incidence of acute GVHD ≥ II at 3 months was 14% (11–16.5) with 10.5% (8–13) for grade III and 7% (5–9) for grade IV; the 1 year cumulative incidence of limited and extensive chronic GVHD were 4% (2–6) and 12.4% (9–16) respectively. After a median follow-up of 18 months (1–106), the median OS was 25 months (16-NR) with a 2 years probability of 50% (43–59). The median PFS was 13.5 months (9–25) with a 2 years probability of 43% (34–50). The cumulative incidence of relapse at 1 year was 31% (27–34), the TRM rate was 6.5% (4.5–8.5) and 20% (17–23.5) at 3 months and 1 year respectively. We performed a multivariate analysis taking into account the patient age, gender, diagnosis, disease status a allo-HSCT, matching variables (sex, ABO, HLA, CMV), conditioning/HSC source and the different serum ferritin levels; the different results are shown in table1. Interestingly, we found that ferritin level >500 has a significant impact on OS which is explained by a significant higher TRM for patients with level >2500 and a significant mortality after relapse in patients with level 500–2500 (figure).The analysis on effect of iron chelating agents is ongoing and results will be communicated later.Serum ferritin level has been previously shown to impact on allo-HSCT survival without a clear explanation of its implication and at which level; in our study, we demonstrated that this survival difference is caused in part by higher TRM and the other part by mortality after relapse.In conclusion, we should give a better attention to iron overload, confer an efficient follow-up of this parameter and provide a treatment strategy after allo-HSCT especially when its level reaches 500μg/l at transplantation. [Display omitted] Disclosures:Nicolini:Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Multivariate Analysis of the Impact of Pre-Treatment Serum Ferritin Level On Response and Overall Survival in Patients with Myelodysplastic Syndromes Treated with Azacitidine

AbstractAbstract 1710 Introduction:Red blood cell (RBC) transfusion dependency independently predicted inferior overall survival (OS) (Itzykson R, et al. Blood. 2011;117:403-11). Transfusion dependency appears to have a major negative prognostic impact in patients with myelodysplastic syndromes (MDS) (Malcovati L, et al. J Clin Oncol. 2005;23:7594-603). The independent prognostic value of development of iron overload on OS and acute myeloid leukemia (AML) risk in MDS has been demonstrated (Sanz G, et al. Blood. 2008;112:abstract 640). Serum ferritin (SF) concentration predicts morbidity and mortality after hematopoietic cell transplantation (Sorror ML, et al. Blood. 2009;114:abstract 651). The prognostic impact of SF on overall response (OR) and OS in patients with MDS treated with azacitidine (AZA) remains unknown. Aim:To analyze the impact of pre-treatment SF levels on response and OS in patients with World Health Organization-defined MDS or AML with 20–30% bone marrow (BM) blasts who received AZA through a compassionate-use program in Spain. Methods:We report a retrospective multivariate analysis of the impact of SF level on OR and OS in patients treated with AZA. Hematologic response was assessed according to International Working Group 2003 (AML) and 2006 (MDS) criteria. SF levels were selected based on median SF value, dividing in two the first half for a better discrimination of the effect (< 500 ng/mL, 500–1000 ng/mL, and > 1000 ng/mL). Comparison of baseline characteristics between SF level groups was performed using Chi-Squared, Fisher’s exact, or Likelihood Ratio Chi-Square test for qualitative variables; and analysis of variance, Mann-Whitney and Wilcoxon, or Kruskal-Wallis test for quantitative variables. A logistic regression model was used to evaluate the effect of pre-treatment variables (ie, SF levels, sex, age, French-American-British classification, BM blast count, time since diagnosis, hemoglobin [Hb] level, International Prognostic Scoring System [IPSS] risk, and thrombocytopenia) on best OR (marrow complete response [mCR] + complete response [CR] + partial response [PR] + hematologic improvement [HI]). A Cox proportional hazards model was used to evaluate the effect of the mentioned variables on OS. All analyses were done using SAS System® version 9.2. Results:Of 240 patients enrolled, pre-AZA SF levels were available for 190 patients. The median pre-treatment SF level was 1001 ng/mL (range 21–5548). Baseline characteristics according to SF levels (< 500 ng/mL [n = 49], 500–1000 ng/mL [n = 46], and > 1000 ng/mL [n = 95]) are summarized in Table 1. OR rates were higher and OS was increased in patients with pre-AZA SF levels of ≤ 1000 ng/mL (Table 2 and Fig). In multivariate analysis, pre-treatment SF levels were predictive of best OR (P = 0.0001). Patients with SF levels > 1000 ng/mL had a reduced likelihood of OR (P < 0.0001 vs SF levels < 500 ng/mL). Baseline SF levels were also predictive of OS (P = 0.0002); patients with SF levels > 1000 ng/mL had the lowest likelihood of OS (P = 0.0012 vs SF < 500 ng/mL; and P = 0.0023 vs SF 500–1000 ng/mL). None of the other variables analyzed had a significant impact on OR or OS. Conclusion:Patients with pre-AZA SF levels > 1000 ng/mL had lower OR rates and inferior OS compared with patients with SF levels ≤ 1000 ng/mL. None of the other patient baseline characteristics analyzed had an impact on these outcomes. Our results suggest that higher OR rates and increased OS are obtained with AZA treatment in MDS patients with SF levels ≤ 1000 ng/mL, compared with patients with SF levels > 1000 ng/mL. This may advocate for early initiation of therapy before increasing SF level; however, prospective controlled clinical trials are needed to confirm this hypothesis. Acknowledgments:Regina Garcia Delgado, Dunia de Miguel, Alicia Bailen, José Ramón González, Joan Bargay, Jose F. Falantes, Rafael Andreu, Fernando Ramos, Mar Tormo, Rafael F. Duarte, Ma José Jiménez Lorenzo, Salut Brunet, Benet Nomdedeu, Antonio Figueredo, Javier Casaño, Llorenç Badiella, and Antonio Fernández Jurado submitted this abstract on behalf of the Asociación Andaluza de Hematología y Hemoterapia, Spain. [Display omitted] [Display omitted] [Display omitted] Disclosures:Garcia Delgado:Celgene Corporation: Research Funding. de Miguel:Celgene Corporation: Speakers Bureau. Bargay:Celgene Corporation: Research Funding. Ramos:Celgene Corporation: Speakers Bureau. Sanz:Celgene Corporation: Speakers Bureau.

Final Results From the Multicenter Compact Study of Complications in Patients with Sickle Cell Disease and Utilization of Iron Chelation Therapy: A Retrospective Medical Records Review.

AbstractAbstract 2106▪▪This icon denotes a clinically relevant abstract Introduction:Over the past few decades, lifespans of sickle cell disease (SCD) patients have increased; hence, they encounter multiple complications. Early detection, appropriate comprehensive care, and treatment may prevent or delay onset of complications. There is a gap in the literature describing the SCD complication rates, blood transfusion patterns, iron chelation therapy (ICT) use, and associated resource utilization in SCD patients ≥16 years old. This study contributes to addressing this gap. Method:Medical records of 254 SCD patients ≥ 16 were retrospectively reviewed between August 2011 and July 2012 at three US tertiary care centers (University of Tennessee: 117; Tulane University: 72; Howard University: 65). Data were collected from patient’s first visit after age 16 (index date) until the earliest indication of death, loss to follow-up, or last patient record on file prior to the centers’ IRB submission dates. Patients were classified into one of three cohorts based on cumulative units of blood transfused and history of ICT: <15 units of blood and no ICT (minimally transfused, Cohort 1 [C1]), ≥15 units of blood and no ICT (Cohort 2 [C2]), and ≥15 units of blood and receiving ICT (Cohort 3 [C3]). SCD complication rates were expressed as the number of SCD complications recorded from patient charts per patient per year (PPPY) and compared among cohorts using rate ratios (RRs). Results:Cohorts 1, 2, and 3 consisted of 69, 91, and 94 patients, respectively. Mean (range) age at index date was similar across cohorts (27 yrs [16–65]) and all patients were African American. Mean length of observation was shorter among patients in C1 (yrs, C1: 6.6; C2: 8.2; C3: 8.1). Post index date, patients in C1 received an average of 1 unit of blood PPPY (p<0.001 vs. C2 and C3), whereas patients in C2 and C3 received an average of 10 and 15 units PPPY (p=0.112), respectively. Among patients with serum ferritin (SF) assessment within 60 days before ICT (n=57), mean (median) SF level was 4,881 ng/mL (4,040). Across all three cohorts, the most common SCD complication was acute pain crisis (69.8%), followed by infection/sepsis (5.1%), leg ulcers (2.9%), and avascular necrosis (2.3%). The rate (95% CI) of any SCD complications was the highest in C2 at 3.02 PPPY (2.89–3.14), followed by 2.26 PPPY (2.16–2.37) in C3, and 1.66 PPPY (1.54–1.77) in C1 (Table 1). Among transfused patients (C2+C3), those receiving ICT were less likely to experience SCD complications than those who did not (RR [95% CI] C2 vs. C3: 1.33 [1.25–1.42]). Similar trends (RR [95% CI]) were observed in emergency room (ER) visits and hospitalizations associated with SCD complications (C2 vs. C3, ER: 1.94 [1.70–2.21]; hospitalizations: 1.61 [1.45–1.78]), but not in outpatient visits. Conclusion:Results from this study highlight the significant burden of complications and the associated healthcare resource utilization for SCD patients. The results suggest that among regularly transfused patients, those who received ICT were less likely to experience complications than those without ICT. However, transfusions are not necessary for all patients with SCD and patients with more complications may have started transfusion therapy earlier. Patients receiving ICT may also receive closer monitoring, which may help with early identification and intervention to delay or prevent the development of complications and improve outcomes. [Display omitted] Disclosures:Jordan:Novartis Pharmaceuticals Corporation: Consultancy, Speakers Bureau. Oneal:Novartis Pharmaceuticals Corporation: Honoraria. Vekeman:Novartis Pharmaceuticals: Research Funding. Bieri:Novartis Pharmaceuticals Corporation: Research Funding. Sasane:Novartis Pharmaceuticals: Employment. Marcellari:Novartis Pharmaceuticals Corporation: Employment. Magestro:Novartis Pharmaceuticals: Employment. Gorn:Novartis Pharmaceuticals Corporation: Research Funding. Duh:Novartis Pharmaceuticals: Research Funding.

A Multicenter, Randomized, Open-Label Trial Evaluating Deferasirox Compared with Deferoxamine for the Removal of Cardiac Iron in Patients with β-Thalassemia Major and Iron Overload (CORDELIA).

Abstract 2124 Background: Without effective iron chelation therapy (ICT), patients with transfusional iron overload are at risk of excess iron-related cardiac complications. Cardiac iron accumulation can be measured using T2* magnetic resonance (normal >20 ms, high risk Methods: Patients with β-thalassemia major, cardiac T2* 6–20 ms, no clinical symptoms of cardiac dysfunction, aged ≥10 yrs, history of ≥50 transfusions, left ventricular ejection fraction (LVEF) ≥56% and liver iron concentration (LIC) ≥3 mg Fe/g dry weight (dw) were recruited. Patients were randomized to an intensified DFO regimen with a target dose of 50–60 mg/kg/d sc for 8–12 hrs, 5–7 d/wk, or deferasirox with a target daily oral dose of 40 mg/kg/d. Dose adjustment recommendations were based on continuous assessment of efficacy and safety markers. Efficacy was assessed in the per-protocol analysis population. Primary efficacy endpoint was change after 1-yr treatment (using last available value ≥150 d after randomization) in cardiac T2* expressed as the ratio of geometric means (Gmean) at end of study (EOS) over baseline (BL) for deferasirox divided by the ratio of Gmeans for DFO. Non-inferiority was pre-defined if the lower limit of the 2-sided repeated 95% confidence interval (CI) for ratio of Gmeans was >0.9. Results: From 925 screened patients, 197 patients (mean age 19.8 ± 6.4 yrs) were randomized. Mean time since start of transfusions was 19.3 and 18.4 yrs in deferasirox and DFO patients, respectively. All patients had received previous ICT. At BL, Gmean cardiac T2* was 11.4 ms; mean ± SD LIC was 29.8 ± 17.5 mg Fe/g dw in deferasirox patients and 30.3 ± 17.9 mg Fe/g dw in DFO patients; median (range) serum ferritin level was 5062 (613–15331) and 4684 (677–13342) ng/mL, respectively. 160 (81.2%) patients completed 1 yr. Mean actual dose of deferasirox was 36.7 ± 4.2 mg/kg/d and DFO was 41.5 ± 8.7 mg/kg/d for 7 d/wk. Overall, Gmean cardiac T2* increased by 12% with deferasirox and 7% with DFO after 1 yr (Fig A). The Gmean ratio between the two arms was 1.0557 (95% CI 0.9981, 1.1331). Lower limit of the 95% CI was >0.9, demonstrating non-inferiority of deferasirox vs DFO, with a trend towards superiority ( P =0.0567). Trends toward increases were observed in patients with severe or mild/moderate cardiac iron (Fig B, C). In patients with BL LIC LVEF was stable with deferasirox (BL 66.9 ± 5.61%; EOS 66.3 ± 5.8%) and DFO (BL 66.4 ± 5.2%; EOS 66.4 ± 5.8%). LIC absolute change from BL was –8.9 ± 11.4 (95% CI –11.5, –6.4) mg Fe/g dw for deferasirox and –12.7 ± 11.4 (–15.3, –10.1) mg Fe/g dw for DFO. Overall adverse event (AE) rates were 67.7% in deferasirox patients and 75.8% in DFO patients. In deferasirox patients, most common AEs were diarrhea (12.5%), proteinuria (11.5%) and influenza (10.4%). Most common AEs in DFO patients were proteinuria (8.8%), upper respiratory tract infection (8.8%) and influenza (6.6%). Serious AEs occurred in 10.7% patients overall (10.4% deferasirox; 11.0% DFO), with many related to the underlying disease. 3 deferasirox patients and 1 DFO patient had 2 consecutive serum creatinine increases >33% above BL and >upper limit of normal (ULN). Overall, 14.6% of deferasirox patients and 3.3% of DFO patients had ALT levels >5xULN and >2xBL. One death (arrhythmia) in the deferasirox arm was considered unrelated to study drug. One death (meningitis) in a DFO patient was suspected to be related to DFO. Discussion: CORDELIA, the first randomized controlled trial comparing deferasirox with DFO for cardiac iron removal, met its primary endpoint in demonstrating non-inferiority of deferasirox vs DFO, with a trend for superiority. There was a trend toward more pronounced improvements in cardiac T2* with deferasirox vs DFO in patients with BL LIC Disclosures: Pennell: Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Siemens: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apotex: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; CVIS: Equity Ownership. Porter: Novartis: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Piga: Novartis: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Lawniczek: Novartis: Employment. Habr: Novartis: Employment. Weisskopf: Novartis: Employment. Zhang: Novartis: Employment. Aydinok: Ferrokin: Research Funding; Novartis: Honoraria, Research Funding, Speakers Bureau.

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

AbstractAbstract 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.Table 1Univariate analyses of EFS, OS and LFSNon chelatedChelated*p-valueMedian EFS arthropathy complications (months), n=236Not reachedNot reached0.794Median EFS diabetes complications (months), n=216Not reachedNot reached0.559Median EFS hepatic complications (months), n=236208Not reached0.303Median EFS cardiac complications (months), n=196901370.004Median OS (months), n=2281051330.009Median LFS (months), n=228Not reachedNot reached0.043*Analysis including patients with ≥3 months chelation (n=109) (of whom 73.4% received deferasirox as first option therapy with a mean dose of 18 mg/kg/day). 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.