Mistry, P. K., M. Balwani, H. N. Baris, H. B. Turkia, A. T. Burrow, J. Charrow, G. F. Cox, S. Danda, M. Dragosky, G. Drelichman, et al., "Addendum to Letter to the Editor: Safety, efficacy, and authorization of eliglustat as a first-line therapy in Gaucher disease type 1.", Blood cells, molecules & diseases, vol. 77, pp. 101-102, 2019.
ElBeshlawy, A., V. Murugesan, P. K. Mistry, and K. Eid, "Reversal of life-threatening hepatopulmonary syndrome in Gaucher disease by imiglucerase enzyme replacement therapy.", Molecular genetics and metabolism reports, vol. 20, pp. 100490, 2019. Abstract

Advanced liver disease complicated by hepatopulmonary syndrome is a recognized complication of Gaucher disease. Macrophage-targeted, recombinant enzyme replacement therapy is effective in reversing clinical manifestations attributed to the accumulation of glycolipid-laden macrophages but it is not known whether advanced fibrotic features of the disease can be ameliorated. We describe a splenectomized patient with Gaucher disease who developed massive hepatomegaly, cirrhosis of the liver and life-threatening hepatopulmonary syndrome. Treatment with Imiglucerase enzyme replacement therapy resulted in dramatic reversal of hepatopulmonary syndrome and liver disease. Our report suggests that Gaucher disease pathology involving advanced fibrosis and life-threatening complications can be reversed by imiglucerase enzyme therapy.

Synopsis: Effect of imiglucerase enzyme replacement therapy on Hepatopulmonary Syndrome in Gaucher Disease.

Repessé, Y., C. Costa, R. Palla, E. F. Moshai, A. Borel-Derlon, R. D'Oiron, C. Rothschild, A. El-Beshlawy, M. Elalfy, V. Ramanan, et al., "Role of factor VIII-binding capacity of endogenous von Willebrand factor in the development of factor VIII inhibitors in patients with severe hemophilia A.", Haematologica, vol. 104, issue 8, pp. e369-e372, 2019.
El-Beshlawy, A., K. Abdel-Azim, A. Abdel-Salam, N. A. Gebril, Y. M. M. Selim, and F. Said, "Clinical Characteristics, Molecular Background, and Survival of Egyptian Patients With Gaucher Disease Over a 20-Year Follow-up.", Journal of pediatric hematology/oncology, 2021. Abstract

This study analyzes the general disease characteristics, impact of enzyme replacement therapy (ERT), and overall survival (OS) of 156 Egyptian patients with Gaucher disease (GD) enrolled on hormone replacement from 1998 to 2017. The mean age at diagnosis was 32.46±12.68 months. Anemia was noted at diagnosis in 50%, thrombocytopenia in 30.7%, severe splenomegaly in 58.7%, severe hepatomegaly in 11.9%, and skeletal findings were detected in 24.3% of the patients. The most prevalent GD type was type 3 (54.5%). Twenty-two of type 3 patients had no neurological manifestations at diagnosis, and 12 developed variable central nervous system manifestations during follow-up. The most common neurological features were limited eye movements, oculomotor apraxia, and squint. Of the 60 patients for whom genotypes were obtained, homozygous L444P was the most common (n=35/60, 58.3%). Treatment with ERT (imiglucerase) revealed significant improvements in blood indices, organ volumes, and growth parameters (P<0.05). Ten (11.7%) type 3 patients did not develop any neurological manifestations under ERT over 20 years. Mortality was 16%, and the 20-year OS was 73.3%. We conclude that in Egypt, type 3 is the most prevalent phenotype of GD, and homozygous L444P is the predominant GBA genotype of GD. Early age at diagnosis and treatment with ERT over 20 years revealed significant improvements in disease manifestations, with an OS of 73.3%.

Kwiatkowski, J. L., M. O. N. A. HAMDY, A. El-Beshlawy, F. S. Ebeid, M. Badr, A. Alshehri, J. Kanter, B. Inusa, A. A. M. Adly, S. Williams, et al., "Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study.", Blood advances, vol. 6, issue 4, pp. 1243-1254, 2022. Abstract

Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.

Musallam, K. M., A. Vitrano, A. Meloni, S. A. Pollina, M. Karimi, A. El-Beshlawy, M. Hajipour, V. Di Marco, S. H. Ansari, A. Filosa, et al., "Risk of mortality from anemia and iron overload in nontransfusion-dependent β-thalassemia.", American journal of hematology, vol. 97, issue 2, pp. E78-E80, 2022.
Musallam, K. M., A. Vitrano, A. Meloni, S. A. Pollina, V. Di Marco, S. H. Ansari, A. Filosa, P. Ricchi, A. Ceci, S. Daar, et al., "Primary HBB gene mutation severity and long-term outcomes in a global cohort of β-thalassaemia.", British journal of haematology, vol. 196, issue 2, pp. 414-423, 2022. Abstract

In β-thalassaemia, the severity of inherited β-globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long-term outcomes remain limited. We analysed data from 2109 β-thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as β /β , β /β , β /β , β /β , β /β , and β /β . Patients were followed from birth until death or loss to follow-up. The median follow-up time was 34·1 years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, β and β mutations showed similar risk profiles. Upon adjustment for demographics and receipt of conventional therapy, patients with β /β , β /β , or β /β had a 2·104-increased risk of death [95% confidence interval (CI): 1·176-3·763, P = 0·011] and 2·956-increased odds of multiple morbidity (95% CI: 2·310-3·784, P < 0·001) compared to patients in lower genotype severity groups. Cumulative survival estimates by age 65 years were 36·8% for this subgroup compared with 90·2% for patients in lower genotype severity groups (P < 0·001). Our study identified mortality and morbidity risk estimates across various genotype severity groups in patients with β-thalassaemia and suggests inclusion of both β and β mutations in strata of greatest severity.

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