bims-conane 2025-02-09 papers

Indian J Hematol Blood Transfus. 2025 Jan;41(1): 112-120

Efficacy and Safety of Mitapivat in Pyruvate Kinase Deficiency: A Systematic Review and Meta-analysis of Clinical Trials.

Hazem E Mohammed, Zeyad Bady, Youssef Z Farhat, Mohamed E Haseeb, Mohamed Nasser, Francis Eshun, Hussien Ahmed H Abdelgawad.

Background: Pyruvate kinase deficiency (PKD), a rare autosomal recessive disease, often leads to chronic hemolytic complications stemming from mutations in the PKLR gene. Mitapivat, an innovative, allosteric activator of the pyruvate kinase enzyme in red blood cells, has emerged as a potential therapeutic agent. This systematic review aims to meticulously evaluate the efficacy and safety of Mitapivat in treating PKD patients.
Methods: We conducted a comprehensive search across three major databases-PubMed, Web of Science, and Scopus-up to November 2023, utilizing a single-arm meta-analysis methodology.
Results: Our analysis included three clinical trials comprising 94 PKD patients. Hemoglobin (HB) levels improved, with an average increase of 1.05 g/dl (95% Confidence Interval [CI]: -0.22 to 2.33). In terms of hemolysis indicators, there was a notable decrease in indirect bilirubin (mean change: -1.36 mg/dl, 95% CI: -3.67 to 0.95) and an increase in haptoglobin (mean change: 0.26 g/L). Patient-reported outcomes (PROs), assessed via the Pyruvate Kinase Deficiency Diary and Pyruvate Kinase Impact Assessment, showed significant improvements, with mean changes of -4.95 (95% CI: -6.711 to -3.19) and - 5.97 (95% CI: -9.87 to -2.06), respectively. Adverse effects were generally mild, with the most common being headache, nausea, elevated alanine aminotransferase, and nasopharyngitis.
Conclusion: Mitapivat substantially improves hemoglobin levels, hemolysis markers, and PROs, maintaining an acceptable safety profile. Nevertheless, additional, larger-scale randomized controlled trials across diverse age groups remain necessary to further corroborate these findings.
Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-024-01830-x.

Keywords: Hemolytic anemia; Mitapivat; PKLR; Pyruvate kinase deficiency

DOI: https://doi.org/10.1007/s12288-024-01830-x

Front Pediatr. 2024 ;12 1487121

Genetic screening strategy for children with hereditary spherocytosis in Jiangxi Province of China.

Chongjun Wu, Zhongjin Xu, Qian Wan, Feng Chen, Yao Ye, Hong Wang.

Objective: This study aims to provide a comprehensive summary of the clinical phenotypic characteristics of children with anemia of unknown etiology, particularly focusing on the early detection of hereditary spherocytosis (HS) and exploring genetic screening strategies for this condition in childhood.
Methods: The study included children with anemia whose underlying cause could not be definitively identified through routine clinical diagnosis. Clinical data was collected and genetic diagnosis of HS was confirmed using next-generation sequencing. Statistical analysis was conducted to evaluate the clinical characteristics of children with HS.
Results: A total of thirty children with unexplained anemia were included in the study, resulting in a gene detection diagnostic rate of 80%. This included the identification of five non-HS-related congenital anemia genes (16.66%, 5/30) and nineteen cases of hereditary spherocytosis (HS). Upon initial diagnosis, the clinical features of HS were not significantly distinct compared to other forms of anemia.
Conclusion: In Jiangxi, China, our strategy of genetic screening for these children is feasible after excluding the common causes of anemia, such as nutritional anemia, G-6-PD deficiency, thalassemia, autoimmune hemolytic anemia, and myelopoietic abnormalities in children. This is an exploration to establish a genetic screening strategy for children with HS, and more detailed genetic screening strategies need to be further studied and explored. Next-generation sequencing remains the main method for the diagnosis and differential diagnosis of HS.

Keywords: China; Jiangxi province; children; genetic screening strategy; hereditary spherocytosis

DOI: https://doi.org/10.3389/fped.2024.1487121

Indian J Hematol Blood Transfus. 2025 Jan;41(1): 167-170

Dual Oral Iron Chelation (DOIC) in Children with Transfusion-Dependent Beta Thalassemia: Real-World Efficacy Data.

Amitoj Singh Chadha, Abaan Ul Haq Khazi Mohammad, Naveen Kanth Dhãmi Nadakuditi, Surbhi Agrawal, Kenson Sam Alex, Namratha S Naik, John Michael Raj, Anand Prakash.

Combination chelation with deferiprone (DFP) and deferasirox (DFX) is one of the treatment modalities for iron overload in children with Transfusion-dependent Thalassemia (TDT). We report our experience with dual oral iron chelation. Retrospective chart review was conducted on all children started on Dual Oral Iron Chelation (DOIC) from 2015 to 2022. Children with TDT requiring DOIC were included in the study. Forty-five children required DOIC. The mean SF before DOIC initiation was 2929 ng/dl (SD 1465.07). The mean ferritin following DOIC was 1962.10 ng/dl (SD 1165.83) at 30 months. Mean duration on DOIC was 44.6 months (IQR 60-30). With DOIC, 82.22% children had a fall in ferritin to < 2000 ng/dl and in 60% of them had fall to < 1000 ng/dL. Dual Oral Iron Chelation (DOIC) is efficacious in reducing ferritin in iron-overloaded patients. Higher ferritin values (> 2500 ng/dL) drop rapidly in the first 12-24 months. DOIC was well-tolerated with no severe adverse effects.

Keywords: Deferasirox; Deferiprone; Serum ferritin; Transfusion-dependent thalassemia

DOI: https://doi.org/10.1007/s12288-024-01804-z