High‐level induction of fetal haemoglobin by pomalidomide in β‐thalassaemia/HbE erythroid progenitor cells

Khamphikham, Pinyaphat; Nualkaew, Tiwaporn; Pongpaksupasin, Phitchapa; Kaewsakulthong, Woratree; Songdej, Duantida; Paiboonsukwong, Kittiphong; Engel, James Douglas; Hongeng, Suradej; Fucharoen, Suthat; Sripichai, Orapan; Jearawiriyapaisarn, Natee

doi:10.1111/bjh.16670

Cited by 6 publications

(7 citation statements)

References 17 publications

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“…Pomalidomide, a third-generation immunomodulatory drug with less AEs, has been proved to be a strong HbF inducer (Khamphikham et al, 2020). If more effective and less embryotoxic thalidomide derivatives are developed, it will be widly used and benefit more thalassemia patients.…”

Section: Discussionmentioning

confidence: 99%

“…So it is necessary to extract the effective components of thalidomide and identify the key mechanisms of thalidomide in the effective treatment of thalassemia. Pomalidomide, a third-generation immunomodulatory drug with less AEs, has been proved to be a strong HbF inducer ( Khamphikham et al, 2020 ). If more effective and less embryotoxic thalidomide derivatives are developed, it will be widly used and benefit more thalassemia patients.…”

Section: Discussionmentioning

confidence: 99%

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Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

Wei

Yang

et al. 2022

Front. Pharmacol.

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At present, the main therapies for ß-thalassemia patients include regular blood transfusion and iron chelation, associating with a number of limitations. Thalidomide, a fetal hemoglobin (HbF) inducer that promotes γ-globin gene expression, has been reported to be effective for ß-thalassemia. Thus, this meta-analysis was conducted to assess the efficacy and safety of thalidomide for treating patients with ß-thalassemia. We searched the related studies from eight databases published from inception until December 1, 2021. The R 4.0.5 language programming was used to perform meta-analysis. After screening of retrieved articles, 12 articles were included that enrolled a total of 451 patients. The Cochrane Collaboration risk assessment tool was used to evaluate the quality and the bias risk of the randomized controlled trials (RCTs), and non randomized trials were assessed using Newcastle-Ottawa Scale (NOS). After treatment with thalidomide, the pooled overall response rate (ORR) was 85% (95% confidence interval (CI): 80–90%), and the pooled complete response rate (CRR) was 54% (95% confidence interval: 31–76%). Compared with the placebo group, the thalidomide group had higher odds of overall response rate (odds ratio = 20.4; 95% CI: 6.75–61.64) and complete response rate (odds ratio = 20.4; 95% CI: 6.75–61.64). A statistically significant increase in hemoglobin level and HbF level after treatment, while there was no statistically significant difference in adult hemoglobin (HbA) level, spleen size, and serum ferritin. According to the results of ORR and CRR, transfusion-dependent thalassemia (TDT) patients showed remarkable efficacy of thalidomide, 83 and 52% respectively. So we analyzed 30 transfusion-dependent thalassemia patients from three studies and found that the most frequent ß-globin gene mutations were CD41-42 (-TCTT), while response to thalidomide did not show any statistically significant relationship with XmnI polymorphism or CD41-42 (-TCTT) mutation. About 30% of patients experienced mild adverse effects of thalidomide. Collectively, thalidomide is a relatively safe and effective therapy to reduce the blood transfusion requirements and to increase Hb level in patients with ß-thalassemia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

Wei

Yang

et al. 2022

Front. Pharmacol.

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“…Thalidomide is an immunomodulatory compound used in clinical practice for the clinical management of multiple myeloma [82,83]. Thalidomide and its derivate pomalidomide have been considered as new therapeutic options for β-thalassemia.…”

Section: Immunomodulators: Thalidomide and Its Derivativesmentioning

confidence: 99%

Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective

et al. 2022

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A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in diseases such as β-thalassemia and sickle cell disease (SCD). While the induction of HbF using lentiviral and genome-editing strategies has been made possible, they present limitations. Meanwhile, progress in the use of pharmacologic agents for HbF induction and the identification of novel HbF-inducing strategies has been made possible as a result of a better understanding of γ-globin regulation. In this review, we will provide an update on all current pharmacological inducer agents of HbF in β-thalassemia and SCD in addition to the ongoing research into other novel, and potentially therapeutic, HbF-inducing agents.

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“…In adults, HbF genes are normally integrated within in hematopoietic stem cells and can be reactivated. Effect of different medications on the increase in the Hg F level has been studied extensively [7] , [8] , [9] , [10] . HbF inducer agents can increase the HbF level by multiple mechanisms, including Janus kinase/signal transducers and activators of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways.…”

Section: Hemoglobin F (Hbf; α2γ2)mentioning

confidence: 99%

“…High rate of side effects is challenging in critical COVID-19 patients. Pomalidomide [8] , [9] , [10] Immunomodulatory drugs Histone acetylation at gamma-globin gene promoter. Acetylation of H3K9 and H3K14 at LCR region of the γ-globin gene and reversing the hemoglobin silencing caused by down-regulation of BCL11A, SOX6, LSD1, GATA1, and KLF1.…”

Section: Hemoglobin F (Hbf; α2γ2)mentioning

confidence: 99%

A hypothesis about the role of fetal hemoglobin in COVID-19

Sotoudeh¹,

Sotoudeh

2020

Medical Hypotheses

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COVID-19 infection is less common in children (with higher fetal hemoglobin levels). In our preliminary study, we also observed a low prevalence and fatality of COVID-19 in countries with high rate of hemoglobinopathy carries. Given these two facts, the hemoglobin structure can play a role in the physiopathology of COVID-19 disease. Several drugs are known to increase fetal hemoglobin in adults. Adding these drugs to COVID-19 clinical trials may improve the patients’ outcomes.

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High‐level induction of fetal haemoglobin by pomalidomide in β‐thalassaemia/HbE erythroid progenitor cells

Cited by 6 publications

References 17 publications

Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective

A hypothesis about the role of fetal hemoglobin in COVID-19

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