Phase 2a Pilot Study to Explore Safety and Efficacy of NBMI Treatment in Patients With Beta Thalassemia Major, Requiring Iron Chelation

2019 ◽  
Author(s):  
Keyword(s):  
Pilot Study ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Safety And Efficacy ◽  
Beta Thalassemia Major

Growth Differentiation Factor 15 (GDF15) and Erythropoietin (EPO) Levels in Beta Talassemia Major Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1881-1881
Author(s):  
Ilaria Salussoglia ◽  
Gisella Volpe ◽  
Silvia Fracchia ◽  
Simona Roggero ◽  
Filomena Longo ◽  
...  
Keyword(s):  
Iron Status ◽  
Clinical Status ◽  
Transferrin Saturation ◽  
Iron Chelation ◽  
Serum Levels ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Transfusion Therapy ◽  
Beta Thalassemia Major ◽  
The Mean

Abstract Background: The serum level of GDF15 has been recently indicated as a possible marker of erythropoiesis (Tanno et al., Nature 2007) suggesting a role of its over-expression in contributing to iron overload in thalassemia syndromes by inhibiting hepcidin expression. The aim of present study has been to evaluate GDF15 serum levels in a homogeneous series of thalassemia patients and the relationship with transfusional parameters and iron status markers. Methods: A group of consecutive patients with beta thalassemia major followed at our institution were included in the study. All patients were on regular transfusion and iron chelation treatment. Quantification of GDF15 on serum samples was performed with DuoSet ELISA for human GDF15 (R&D Systems) following the manufacturer’s protocol (Tanno et al., Nature 2007). Each patient had also a blood test for haemoglobin (Hb), serum iron, ferritin, transferrin, transferrin saturation and EPO levels. Liver Iron Concentration by SQUID and cardiac iron by MRI T2* have been assessed. The mean hemoglobin levels of the previous year (pre-transfusional, post-transfusional and mean) have been calculated for each individual. The presence of mild thalassemic mutations was used to classify mild or severe genotype. Clinical status has been assessed on the presence/absence of main complications (heart disease, liver disease, diabetes, hypothyroidism). Statistical analysis was performed using the software Statistica (StatSoft). Results: One hundred-forty patients (73 male, 67 females) were studied. The mean age was 27.9 ± 9.0 years (range: 3.5–42). One hundred (71%) were splenectomised. Betathalassemia major patients had elevated GDF15 serum levels (mean 6892 ± 6894 pg/mL; range 720–52521) in comparison with healthy volunteers (273 ± 104 pg/mL; range 129–401). GDF 15 levels were strongly related to EPO levels (r=0,81; p<0,001). GDF15 levels were not related with age, gender, spleen, clinical status and iron markers. Patients with a severe genotype had higher GDF15 levels than mild genotype patients. GDF15 levels had a negative correlation with Hbs (p<0,05 for actual Hb and pre-transfusional Hb; p<0,001 for post-transfusional Hb and mean Hb). In thalassemia major patients with a severe genotype, GDF15 levels within thrice the normal range have been observed only in patients with pre-transfusional Hb above 9,6, post-transfusional Hb above 12,5 and a mean Hb above 11,3. Conclusions: In beta thalassemia major patients on regular transfusion and iron chelation, serum GDF15 levels are high, inversely related to the haemoglobin levels maintained. Further studies of this marker may lead to a rethinking of the optimal transfusion therapy in these conditions.

Cardioprotection by Deferiprone[L1] Inspite of Rising Serum Ferritin in Beta Thalassemia Major Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3816-3816
Author(s):  
Anil Pathare ◽  
Shahina Daar ◽  
Salam Alkindi ◽  
J.David Dennison
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Myocardial Performance ◽  
Beta Thalassemia Major ◽  
One Year ◽  
Fractional Shortening ◽  
Paired T Test

Abstract Background: Iron overload is the main cause of morbidity and mortality especially from heart failure in patients with beta thalassemia major (TM). Successful iron chelation is therefore essential for the optimal management of TM. Although desferrioxamine (DFX) has been the major iron-chelating treatment of transfusional iron overload, compliance is a major hindrance in achieving optimal therapeutic results. The availability of oral iron chelation with deferiprone (L1) is useful but shows poor efficacy when used alone as compared to DFX. We observed that inspite of rising serum ferritin, these patients benefit by an improvement in the myocardial performance parameters indicating a cardioprotective effect of L1 inspite of worsening of transfusional iron overload. Aim: To study the cardioprotective efficacy of L1 in a prospective study over one year in beta thalassemia major patients with transfusional overload by echocardiography. Methods: We studied 23 patients [M:F;12:11] with beta thalassemia major (Mean age + SD, 19.48 + 5.02; Range 13–32 years) attending the Day Care unit for regular transfusional support. They received packed red cells every 3–4 weeks to maintain pre-transfusion hemoglobin concentration above 9 g/dl. They had been receiving DFX at a daily dose of 40mg/kg/day by subcutaneous infusion for 8–10 hrs on 4–5 nights each week for past several years. However, due to various reasons, they had developed considerable transfusional iron overload and could not continue to use DFX owing to poor compliance. These patients were allocated to prospectively receive therapy with oral iron chelator L1 [Deferiprox-APOTEX] at 75mg/kg body weight in three divided doses with food after informed consent. They were observed and examined regularly at monthly intervals when they came for regular blood transfusions. Cardiac evaluation was performed with a yearly assessment of ECG and echocardiography. Iron overload assessment was performed by serial serum ferritin levels every two months. It being an acute phase reactant, ESR and C-reactive protein were also estimated whenever needed to validate the utility of ferritin levels as a marker of iron overload. Results: Over the one year study period, the mean serum ferritin rose dramatically from 5209 ng/ml to 6792 ng/ml (p<0.004;paired t test). Interestingly, over the same period there was a significant improvement in the myocardial function as assessed by the Ejection fraction which improved from 68.22% to 73.87% (p<0.0001) and Fractional shortening which also rose from 33.45% to 37.44% (p<0.0001). Improved myocardial performance inspite of progressive worsening of iron overload with Deferiprone therapy for one year[n=23] SF Pre L 1 SF After one year EF Pre L 1 EF After one year FS Pre L 1 FS After one year SF-Serum Ferritin ng/ml;EF-Ejection Fraction%;FS-Fractional Shortening% Mean 5209 6791 68.22 73.87 33.45 37.45 ±SD 2638 4271 5.3 4.8 4.06 4.42 Range - Min 2006 3395 58 62 25.2 29.9 Range - Max 14000 20000 75 88 42 51.1 Students paired ‘t’ test p<0.004 p<0.0001 p<0.0001 Summary/Conclusion: The study emphasizes that beta thalassemia major patients with transfusional iron overload who receive L1 at 75 mg/kg/day as their main chelation therapy show progressive iron overloading. However, inspite of this there is a silver lining is as much as that this treatment has a significant cardio protective effect as shown by the improvement in the echocardiographic parameters of myocardial performance in these patients under study.

Thiotepa in the Conditioning Regimen Decreases Rejection after HLA Identical Allogeneic Marrow Transplantation in Children with Beta Thalassemia Major Aged Less Then 4 Years

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4598-4598
Author(s):  
Paola Polchi ◽  
Javid Gaziev ◽  
Guido Lucarelli ◽  
Pietro Sodani ◽  
Cecilia Alfieri ◽  
...  
Keyword(s):  
Relapse Rate ◽  
Conditioning Regimen ◽  
Iron Chelation ◽  
Rejection Rate ◽  
Thalassemia Major ◽  
Organ Damage ◽  
Beta Thalassemia ◽  
Beta Thalassemia Major ◽  
Gvhd Prophylaxis ◽  
Class 1

Abstract BMT in children with beta thalassemia major is the only form of definitive cure with correction of the genetic disease in a relevant proportion of patients, and long term thalassemia free survival. Lucarelli and coll. showed since 1986 that transplant performed early in the course of disease gives high chance of cure, and a system of class definition was reported in 1990 identifying as in class 1 patients without any evidence of organ damage, based on hepatomegaly, presence of liver fibrosis and history of regular or irregular iron chelation. Majority of children aged less then four years were then in class 1 and occasionally in class 2. Thiotepa has been introduced in the conditioning regimen of children less then 4 y.o. in the attempt to decrease the rejection rate in this category of good prognosis patients. Out of 519 children affected by not advanced Beta Thalassemia Major, either in class 1 or 2 of risk, with an HLA identical sibling donor, 25 patients aged 1 to 4 yo received an intensified conditioning regimen including thiotepa 10 mg/kg given in one day, in addition to standard BUS-CY regimen called PC 6. This was based on the observation that children aged below 4 transplanted after the standard PC 6 had significantly higher relapse rate with return to thalassemic pre transplant condition (OS, TFS, REJ were 87%; 86%; 4% vs 87%; 73%; 14% in children aged above or below 4 yo respectively (n=398 =>4; n=96 < 4). The increased relapse rate was more relevant in children treated with standard PC 6 and GVHD prophylaxis performed using short MTX plus CSA versus those who received cyclosporine alone. The GVHD prophylaxis protocol including sMTX + CSA +Pred, used after 1999 for all patients in our practice significantly improved OS, lowered GVHD rate, but had a trend toward increased rejection rate. This trend was more evident in children aged less than 4 despite an increased dose of Busulfan (16 mg/kg total) was already in use for younger children. Therefore, since 2003 we introduced Thiotepa for children less then 4 yo, maintaining the GVHD prophylaxis with sMTX and CSA. In the last group of 25 children aged below 4 receiving the intensified protocol, 1 patient rejected the graft and had thalassemia recovery, one died of GVHD and infection, and 23 are alive and cured. Actuarial probability of OS, TFS, Rejection were 96%; 91%, 5%. These results favourably compare to the previous results in this category of patients, confirming that Thiotepa exerts additional immunosuppressive and eradicating action, counteracting the effect of GVHD prophylaxis with sMTX+CSA, that exerts an action favouring rejection.

scholarly journals Iron chelation therapy needed for serum ferritin overloaded patients of beta thalassemia major

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wasim Muhammad ◽  
Muhammad Ishaq ◽  
Muhammad J. Khan ◽  
Umair Ahmad ◽  
Muhammad Waseem
Keyword(s):  
Serum Ferritin ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Care Facility ◽  
Health Care Facility ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Cross Sectional ◽  
Beta Thalassemia Major ◽  
Khyber Pakhtunkhwa Province

The main objective of the current study is to evaluate the level and overload of serum ferritin in multi-transfused beta Thalassemia major patients. There is an earnest need to defend the chelation treatment and to make mindfulness about the results of serum ferritin in the patients beta Thalassemia major. This is a Cross sectional analytical study performed in Fatimid foundation Hayatabad, Peshawar, Khyber Pakhtunkhwa province of Pakistan. Those patients who has beta thalassemia major are included in this study. In this study there are total 108 patients in which 54 males and 54 females. The highest mean of serum ferritin level in the category of male was in the age of 12 years were finds 8160.5 ng/mL. Among the female the highest mean of ferritin level was in the age of 17 years were finds 13,349.5 ng/mL. In this study majority of patient’s revealed much high levels of serum ferritin. These levels reveal insufficient chelation. Appropriate chelation of iron load can improve the quality of the life of these patients. The low level of education, Poverty problems, and insufficient health care facility of are the main obstacle in the effective management of ferritin overload in thalassemia patients.

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