Efficacy of deferasirox median dose of 30 mg/kg /day in pediatric patients with β- thalassemia major during one year follow- up therapy.

Author(s):  
Nashwan M Al-Hafidh ◽  
Mozahim S. Younis

Objective: To assess the efficacy of deferasirox median dose of 30 mg /kg /day in pediatric patients with β- thalassemia major during one year of follow up Patients and methods: This study was conducted at Ibn Al Atheer center of thalassemia, Mosul city, Iraq during the period from 3rd of February 2013 to 2nd of February 2014. Serum ferritin was measured at baseline and at four weekly intervals thereafter among 49 transfusion dependent children with β-thalassemia major, who were treated with median deferasirox dose of 30 mg /kg /day. Results: No statistically significant difference was detected between mean serum ferritin level at baseline (2189.39 ± 85.7) ng/mL and its mean value at four weekly intervals during forty-eight weeks of deferasirox therapy. There was significant (p = 0.027) improvement of serum ferritin at fifty – two weeks reading (1750.6 ± 202.8 ng/mL) compared to baseline reading. Percentage of patients with baseline serum ferritin levels of >2,500 ng/ml was 32.7% (16/49), which increased significantly (p=0.000) to 65% at four weeks of therapy, and ranged between 32.1% - 46.2 % in the remaining readings. Conclusions: There was no significant reduction of serum ferritin during initial forty-eight weeks of deferasirox median dose of 30 mg /kg /day among patient with baseline mean serum ferritin above 2000 ng /ml.

Healthcare ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 90
Author(s):  
Sheena Henry ◽  
Lu Shi ◽  
Virginia Alexander ◽  
Richard O’Neal ◽  
Stephen Carey ◽  
...  

We examined the impact of a group-based self-empowerment intervention among diabetes patients, which uses multidisciplinary education, collaborative learning, peer support, and development of diabetes-specific social capital to improve glycemic control and weight management. Thirty-five patients who had primary care established at the Prisma Health Upstate, Internal Medicine Resident clinic and held the diagnosis of diabetes for longer than one year were recruited for our single-arm pilot intervention. Each group intervention session involved one to two internal medicine resident physician facilitators, a clinical diabetic educator, and 5–10 patients. Each session had a framework facilitated by the resident, with most of the discussion being patient-led, aiming to provide a collaborative learning environment and create a support group atmosphere to encourage self-empowerment. Patients’ hemoglobin A1c level and body mass index (BMI) before the intervention and 3 to 6 months after completion were collected from the laboratory results obtained in the participants’ routine clinic visits. All graduates from this three-week intervention were invited to attend monthly maintenance sessions, and we tracked the HgbA1c measures of 29 JUMP graduates one year after the intervention, even though 13 of the 29 chose not to participate in the monthly maintenance sessions. The pre-intervention HgbA1c level averaged 8.84%, whereas the post-intervention HgbA1c level averaged 7.81%. A paired t test showed that this pre–post difference of 1.03 percentage points was statistically significant (p = 0.0007). For BMI, there was an average decline of 0.78 from the pre-intervention mean value of 40.56 to the post-intervention mean value of 39.78 (p = 0.03). Among the 29 participants who agreed to participate in our follow-up measure of their HgbA1c status one year after the intervention, a paired t test showed that there was no significant difference between the post-JUMP measure and the follow-up measure (p = 0.808). There was no statistically significant difference between the HgbA1c level of those participating in the maintenance program and that of those not participating (post-intervention t test of between-group difference: p = 0.271; follow-up t test of between-group difference: p = 0.457). Our single-arm, pilot study of the three-week group intervention of self-empowerment shows promising results in glycemic control and weight loss. The short duration and small number of sessions expected could make it more feasible for implementation and dissemination as compared with popular intervention protocols that require much longer periods of attendance, if the effectiveness of this patient group-based self-empowerment approach can be further established by randomized controlled studies in the future.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3649-3649 ◽  
Author(s):  
Yoo-Hong Min ◽  
Hyeoung Joon Kim ◽  
Kyoo Hyung Lee ◽  
Sung-Soo Yoon ◽  
Jae Hoon Lee ◽  
...  

Abstract Transfusion-related iron overload and its consequences are emerging challenges in chronically transfused patients with myelodysplastic syndromes (MDS) or aplastic anemia (AA). Measurement of liver iron concentration (LIC) is used as a surrogate for total iron burden to guide chelation therapy in transfusion-dependent patients. Although deferasirox (Exjade®, ICL670) is an oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis, the clinical data on its specific benefits of iron chelation, including reduction of LIC, in transfusion-related iron overload patients with MDS or AA has been limited. We have prospectively investigated the efficacy of deferasirox for iron chelation by serial measurement of serum ferritin level and LIC, which is measured in vivo using quantitative tissue proton transverse relaxation rates (R2) magnetic resonance imaging (MRI), in transfusional iron overload patients with MDS or AA. Here we report the interim analysis data. A total of 79 patients with de novo MDS (n = 29) or idiopathic AA (n = 50) showing serum ferritin level over 1,000ng/ml were enrolled from 23 institutes. All patients were regularly transfused and received a median of 30 red blood cells (RBC) units in the year prior to the start of the study. Among MDS cases, 3 (10.3%), 20 (69.0%), and 4 cases (13.8%) were categorized as IPSS low-risk, intermediate-1-risk, and intermediate-2-risk group, respectively. In AA cases, 34 (64%) were severe form. Mean value of serum ferritin level in enrolled patients was 4,417 ± 3,378 (4,788 ± 3,996 in MDS, 4,185 ± 2,962 in AA) ng/ml at the time of deferasirox initiation. LIC value was measured using quantitative R2 MRI and FerriScan (Resonance Health, Australia) analysis. Mean value of LIC was 23.9 ± 13.8 (26.1 ± 15.0 in MDS, 22.8 ± 13.2 in AA) mg Fe/g dry weight. Linear regression analysis indicated a close correlation between serum ferritin level and LIC (r=0.55, p<0.001). Deferasirox was given orally at a dose of 20 mg/kg/day for at least 6 months to all patients. If the serum ferritin falls below 500 ng/ml, treatment was withheld. A consistent decrease in the serum ferritin level was demonstrated during the first 6 months in vast majority of patients despite of continued transfusion (209.7 ± 159.9 ng/ml and 324.0 ± 289.4 ng/ml per month in MDS and AA, respectively). Over the study period, patients with MDS or AA received a mean of 3.7 and 2.7 units RBC per month, respectively. After 6 months of medication, a slower decrease in the serum ferritin level was observed in MDS patients. In 30 cases, one-year medication of deferasirox was completed. At the end of study (EOS), the serum ferritin levels were significantly decreased to 3,085 ± 2,150 ng/ml (64.4% of baseline level) and 2,913 ± 2,232 ng/ml (69.6% of baseline level, p<0.01) in MDS and AA, respectively. One-year follow-up R2 MRI could be evaluated in 24 cases, and LIC was significantly decreased to the level of 19.3 ± 13.6 mg Fe/g dry weight (67.4% of baseline value, p=0.01). Decrease in the level of LIC at EOS in MDS (64.3% of baseline) was comparable to that in AA cases (68.5% of baseline). The most common drug-related adverse events (AE) were gastrointestinal disturbances, non-progressive increase in serum creatinine, and skin rash. However, AE were transient and mild-to-moderate in severity. Deferasirox was discontinued in 28 (35.4%) cases because of death (7 in MDS and 6 in AA), patient refusal (11 cases), and decrease in the serum ferritin level below 500ng/ml (4 cases). All death was ascribed to disease-related causes including cytopenia in nine (11.4%) and disease progression in one (1.3%). This study clearly shows that deferasirox is effective in reducing LIC and serum ferritin level in transfusional iron overload patients with MDS or AA, even with ongoing transfusion requirement, and well tolerated. Careful assessment of patient’s transfusion requirement will be important in making dose adjustment according to purpose of iron chelation. Data from extension phase of this clinical trial may expand our knowledge about the beneficial effects of deferasirox on prolonging survival and improving quality of life in these patients.


2020 ◽  
Vol 19 (3) ◽  
pp. 453-457
Author(s):  
Nashwan M Al Hafidh ◽  
Mozahim S Younis

Objectives: Abnormal liver function tests lead to interruptions of Deferasirox therapy. The aim of this study is to determine the changes in liver transaminases levels in pediatric patients with β -thalassemia major during one year follow up of Deferasirox treatment. Material and methods: This study was conducted at Ibn Al Atheer center of thalassemia, Mosul city, Iraq during the period from 3rd of February 2013 till 2nd of February 2014. Seventy one pediatric patients with β -thalassemia major were included in the study. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured every 4 weeks after starting Deferasirox therapy dose of 30 mg /kg/day for one year. Results: In comparison to mean baseline ALT values, there were significant elevations of mean ALT values in each of the subsequent 4-weekly interval readingsafter Deferasirox therapy. There was nearly eleven times relative risk of having ALT ≥ 5 upper normal level (UNL) in patient with abnormal baseline ALT (Odd ratio 10.96,95% Confidence Interval: lower 2.05, upper 58.58). During a year of study, Deferasirox therapy was associated withALT readings of ≥ 5UNL in 22(31%) of pediatric β-thalassemia patients and that elevation lasted for 4 weeks in 95.5% of patients. Conclusions: Elevated ALT of ≥ 5UNL after Deferasirox therapy was short- lived, and lasted for 4 weeks in 95.5% of patients. It is advisable to start Deferasirox therapy at a dose of 30 mg /kg / day when baseline ALT level is normal. Bangladesh Journal of Medical Science Vol.19(3) 2020 p.453-457


2017 ◽  
Vol 24 (02) ◽  
pp. 315-321
Author(s):  
Asma Mehreen ◽  
Saeeda Bano ◽  
Bushra Ujala

Introduction: β-Thalassemia major (β-TM) is a genetic haemoglobin disorderwhich is relatively common in some geographical areas. β-TM is characterized by severe anaemia,which needs a continuous blood transfusion regimen starting from the first months of life toprolong survival. Objectives: To compare mean reduction in serum ferritin level with deferasiroxand desferrioxamine when used as an iron chelator in multi-transfused beta thalassemia major.Study design: Randomized controlled trial. Setting: Thalassemia clinic, The Children’s Hospitaland The Institute of Child Health, Lahore. Duration of Study with Dates: Study was carried outover a period of nine months from 28-06-2015 to 27-03-2016. Subjects and Methods: A totalof 100 patients (50 patients in each group). The patients were randomly allocated into twogroups using random numbers stable. Group-A received Deferasirox and group-B receivedDesferrioxamine. Results: Mean age of the patients was 7.42±4.13 and 7.87±4.13 in group-Aand B, respectively. Regarding sex distribution, 26 patients (52.0%) in group-A and 28 patients(56.0%) in group-B were male while 24 patients (48.0%) in group-A and 22 patients (44.0%) ingroup-B were female. Reduction from baseline in group-A was 783.60±413.66 ng/ml and ingroup-B 552.80±155.45 ng/ml (P<0.001) There was more reduction in group-A. In group-Abaseline serum ferritin level was 2495.00±1259.10 ng/ml and at 9 month 1712.00±1019.36 ng/ml (P<0.001). Similarly in group-B baseline serum ferritin level was 2422.80±910.43 ng/ml andat 9 month 1883±862.72 ng/ml (P<0.001). Conclusion: In conclusion, deferasirox was moreeffective in terms of reduction in serum ferritin level when compared with desferrioxamine inmulti-transfused beta thalassemia major patients.


Author(s):  
Afshin Fathi ◽  
Majid Vafaie ◽  
Firouz Amani ◽  
Nadia Mohebbi

Background: Beta thalassemia is one of the inherited blood diseases in which the production of specific chains in hemoglobin decreases. Esfarlal is a shaltor which is used in these patients as a single dose per day. Since it is prescribed orally, it is easier to tolerate the drug and control the serum iron level of the patient. The aim of this study was to evaluate the efficacy of Osveral in reducing ferritin levels in patients with thalassemia major.Methods: This quasi-experimental study was performed on 48 patients with thalassemia major who referred to Bu-Ali hospital for receiving blood. At the beginning of the study, the required data were collected along with patients' tests including hemoglobin, ferritin, TSH, T4, CBC diff, BUN AST, ALT, BS and creatinine CBC diff. The Osveral drug was prescribed and the patients were evaluated monthly for up to 6 months on the basis of complications. In the first three months after the start of the drug, the serum ferritin level was measured, the dose was adjusted and 6 months after late, the previous tests were again requested, and the auditory and visual examinations were performed, and the information entered the checklist. Data were analyzed using SPSS statistical software.Results: Among all patients, 27 (56.2%) were male and the rest were women with a mean age of 22.22 ± 8.77 years. The results showed that during one year of study, hemoglobin level increased and ferritin level decreased significantly, and other parameters didn’t show significant difference. Nausea and vomiting were the most common complications among patients, which was higher after Osveral than before receiving Osveral.Conclusions: Results showed that Osveral is effective in reducing the level of ferritin in patients with thalassemia major, but control of hematuria is recommended when using this drug.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2916-2916
Author(s):  
Sophie Park ◽  
Rosa Sapena ◽  
Dominique Vassilieff ◽  
Charikleia Kelaidi ◽  
Dominique Bordessoule ◽  
...  

Abstract Abstract 2916 Background: Increased serum ferritin (SF) level has been associated with worse overall survival (OS) in lower risk MDS, presumably though iron overload in vital organs including the heart and liver (Cazzola, NEJM 2005, Malcovati, JCO 2005, Garcia-Manero G et al. Leukemia 2008). However, those high levels are generally associated with RBC transfusion requirement (Malcovati, JCO 2007, Sanz, Blood (ASH 2008 : Abstract 640). High SF level has also been reported in non transfused lower risk MDS, and attributed mainly to ineffective erythropoiesis, but its prognostic value in this context is unclear. We evaluated the prognostic value of SF level at diagnosis in lower risk non transfusion dependent (TD) MDS patients included in the GFM registry of MDS. Methods: We selected in the GFM Registry (1900 pts included between mid 2003 and 2010), 485 newly diagnosed IPSS low and int 1 (lower) risk MDS patients (pts), not transfused during the first 6 months of follow-up, who had a baseline SF level (normal values 20–300 ng/ml), and no other cause of increased SF, including infection and liver disease (due in particular to alcohol abuse). Pts with SF < 20ng/mL were excluded. The prognostic value of SF for AML progression and OS was analyzed. Results: Median age of the 485 pts was 77 years (range 29–103), with 53.8% males. WHO classification was RA 21.5%, RCMD 23.5%, RARS 23%, RCMD-RS 0.5%, RAEB-1 22% and 5q- syndrome 5%. Karyotype according to IPSS was fav (61%), int (10%), unfav (2%), not available (17%). IPSS was 0 (44%), 0.5 (31%), 1 (8%), ND (17%). The median level of SF was 276ng/ml (range 20–5558) with 225 (46%), 145 (30%) and 47(10%) pts having SF>300ng/ml, >500ng/ml and >1000ng/ml respectively (resp.). In univariate analysis, male gender (P=0.0005), Hb level<10g/dl (P=0.0013), MCV >100μm3 (P=0.02), erythroblasts >30% in bone marrow (P=0.008), serum (s) EPO level>100IU/l (P=0.04), RARS (P<0.0001) were significantly associated with increased SF level (ie. >300ng/ml) while karyotype, IPSS, % marrow blasts, reticulocytes, platelets showed no correlation. In multivariate analysis, sEPO level>100IU/l and RARS were significantly associated with higher SF level. As the SF threshold of 1000ng/mL is often proposed to start chelation therapy, prognostic analyses were also made for that level. Hb level <10g/dl, and sEPO level>100 were associated with SF >1000 ng/ml in univariate analysis, while only Hb level<10g/dl still showed a correlation in multivariate analysis. 5-year OS was 77% and 85% in pts with baseline SF<300 and >300ng/ml resp. (p=0.7) and 81% vs 92% for SF<1000 and >1000ng/ml, resp. (p=0.11) and 5-year cumulative incidence of AML transformation was 2.2% and 3.3% for pts with SF<300ng/ml and >300ng/ml resp (P=0.69), and 3% and 0% for pts with SF<1000ng/ml and >1000ng/ml resp (P=0.86). Conclusions: Increased baseline SF level in non transfusion-dependent lower risk MDS is correlated with a few baseline characteristics including more severe anemia, a diagnosis of RARS and higher baseline serum EPO level, but is not significantly correlated with outcome. Disclosures: Fenaux: CELGENE: Honoraria, Research Funding; JANSSEN CILAG: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; GSK: Honoraria, Research Funding; NOVARTIS: Honoraria, Research Funding; MERCK: Honoraria, Research Funding; CEPHALON: Honoraria, Research Funding.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2168-2168
Author(s):  
Osamu Kondo ◽  
Kohei Higuchi ◽  
Mariko Shimizu ◽  
Azusa Mayumi ◽  
Kanako Isaka ◽  
...  

Abstract Background Previous studies showed an association between iron overload and hematopoietic transplant complications. Serum ferritin is widely used as an indicator for iron stores and an elevated pretransplantation level was strongly associated with inferior outcomes of transplantation in adults, though it has not been clarified well in pediatric patients. We studied prognostic impact of pretransplantation elevated ferritin levels on outcomes of allo-HSCT for pediatric hematological diseases. Patients and Methods We studied 93 consecutive pediatric patients (< 18 years old) with hematologic disease who underwent allogeneic HSCT at Osaka Medical Center and Research Institute for Maternal and Child Health between 2003 and 2009 in whom pretransplantation serum ferritin levels were available. The patients were divided into two groups, pretransplantation serum ferritin level ≥ 1000 ng/mL (SF≥1000) and ferritin level < 1000 ng/mL (SF<1000). Survival rate was estimated using the Kaplan-Meier method and compared between the two groups using the log-rank test. The association of pretransplantation ferritin and the transplant outcomes was evaluated in multivariate analysis with Cox proportional-hazards regression model. Results At 5 years after transplant, children in SF≥1000 (n=51) had a significantly lower overall survival (OS; 42.1% vs 76.6, p=0.001) and a higher non-relapse mortality (NRM; 41.0% vs 18.6%, p=0.018) than those in SF<1000 (n=42). SF≥1000 (n=20) in patients with leukemia in nonCR had lower OS (14.4% vs 75.0%, p=0.051) than SF<1000 (n=5), whereas patients in CR had almost the same OS (65.8% vs 62.2%, p=0.920) between SF≥1000 (n=14) and SF<1000 (n=14), although the sample size was too small to detect statistically significant difference. Univariate analyses revealed elevated ferritin level, leukemia, nonCR, GVHD grade 3-4 and haploidentical donor as significant worse prognostic factors for OS and cord blood transplant as a significant better factor. In multivariate analysis, an elevated pretransplantation serum ferritin level was the only significant prognostic factor for worse overall survival [HR(95%CI): 2.35 (1.05-5.27), p=0.038]. There was no significant difference in the incience of acute GVHD, infection and any other complications as causes of nonrelapse death between the two groups, although the total incidence of fatal transplant-related complications was significant higher in SF≥1000. Conclusion Our results indicate that an elevated pretransplant serum ferritin level adversely affects outcomes of allogeneic transplantation in pediatric patients as reported in adults. The adverse impact of elevated ferritin levels on survival resulted from increased NRM. The association between high ferritin levels, which are usually caused by iron overload, and outcomes of transplantation in pediatric patients requires further prospective studies. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 234-236
Author(s):  
P Willems ◽  
J Hercun ◽  
C Vincent ◽  
F Alvarez

Abstract Background The natural history of primary sclerosing cholangitis (PSC) in children seems to differ from PSC in adults. However, studies on this matter have been limited by short follow-up periods and inconsistent classification of patients with autoimmune cholangitis (AIC) (or overlap syndrome). Consequently, it remains unclear if long-term outcomes are affected by the clinical phenotype. Aims The aims of this is study are to describe the long-term evolution of PSC and AIC in a pediatric cohort with extension of follow-up into adulthood and to evaluate the influence of phenotype on clinical outcomes. Methods This is a retrospective study of patients with AIC or PSC followed at CHU-Sainte-Justine, a pediatric referral center in Montreal. All charts between January 1998 and December 2019 were reviewed. Patients were classified as either AIC (duct disease on cholangiography with histological features of autoimmune hepatitis) or PSC (large or small duct disease on cholangiography and/or histology). Extension of follow-up after the age of 18 was done for patients followed at the Centre hospitalier de l’Université de Montréal. Clinical features at diagnosis, response to treatment at one year and liver-related outcomes were compared. Results 40 patients (27 PSC and 13 AIC) were followed for a median time of 71 months (range 2 to 347), with 52.5% followed into adulthood. 70% (28/40) had associated inflammatory bowel disease (IBD) (78% PSC vs 54% AIC; p=0.15). A similar proportion of patients had biopsy-proven significant fibrosis at diagnosis (45% PSC vs 67% AIC; p=0.23). Baseline liver tests were similar in both groups. At diagnosis, all patients were treated with ursodeoxycholic acid. Significantly more patients with AIC (77% AIC vs 30 % PSC; p=0.005) were initially treated with immunosuppressive drugs, without a significant difference in the use of Anti-TNF agents (0% AIC vs 15% PSC; p= 0.12). At one year, 55% (15/27) of patients in the PSC group had normal liver tests versus only 15% (2/13) in the AIC group (p=0.02). During follow-up, more liver-related events (cholangitis, liver transplant and cirrhosis) were reported in the AIC group (HR=3.7 (95% CI: 1.4–10), p=0.01). Abnormal liver tests at one year were a strong predictor of liver-related events during follow-up (HR=8.9(95% CI: 1.2–67.4), p=0.03), while having IBD was not (HR=0.48 (95% CI: 0.15–1.5), p=0.22). 5 patients required liver transplantation with no difference between both groups (8% CAI vs 15% CSP; p=0.53). Conclusions Pediatric patients with AIC and PSC show, at onset, similar stage of liver disease with comparable clinical and biochemical characteristics. However, patients with AIC receive more often immunosuppressive therapy and treatment response is less frequent. AIC is associated with more liver-related events and abnormal liver tests at one year are predictor of bad outcomes. Funding Agencies None


Hemoglobin ◽  
2021 ◽  
Vol 45 (1) ◽  
pp. 69-73
Author(s):  
Salah H. AL-Zuhairy ◽  
Mohammed A. Darweesh ◽  
Mohammed A-M. Othman

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