Thalidomide for Patients With Thalassemia Intermedia: A Retrospective Multicenter Clinical Study

Yang, Kun; Wu, Yi; Zhou, Yali; Zhou, Tianhong; Wang, Li; Geng, Zhili; Yin, Xiaolin

doi:10.4084/mjhid.2020.021

Cited by 27 publications

(38 citation statements)

References 27 publications

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“…A total of 109 articles were retrieved from the search strategy. After screening of title, abstract, and full-text of those articles, 12 articles were included for analysis ( Chen et al, 2017 ; Li et al, 2018 ; Ren et al, 2018 ; Jain et al, 2019 ; Begum et al, 2020 ; Islam et al, 2020 ; Nag et al, 2020 ; Sen et al, 2020 ; Yang et al, 2020 ; Yassin, 2020 ; Chen et al, 2021 ; Li et al, 2021 ), which enrolled 451 patients. Jain et al conducted a RCT and compared hydroxyurea arm with thalidomide arm, while only thalidomide arm was included in the present meta-analysis ( Jain et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

“…ORR was assessed in 10 studies ( Chen et al, 2017 ; Li et al, 2018 ; Ren et al, 2018 ; Jain et al, 2019 ; Nag et al, 2020 ; Sen et al, 2020 ; Yang et al, 2020 ; Yassin, 2020 ; Chen et al, 2021 ; Li et al, 2021 ). Five studies included both TDT and NTDT patients ( Chen et al, 2017 ; Li et al, 2018 ; Sen et al, 2020 ; Yang et al, 2020 ; Yassin, 2020 ), and the outcomes of TDT and NTDT patients were separated in the original manuscripts, so we analyzed the data in these studies respectively. Chen et al conducted a RCT included thalidomide group and placebo group ( Chen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…The pooled ORR was 85% (95% CI: 80–90%, I 2 = 38%, p = 0.07), and the pooled ORR values in two subgroups were different. Seven studies reported the ORR of NTDT patients after the treatment of thalidomide ( Chen et al, 2017 ; Li et al, 2018 ; Ren et al, 2018 ; Jain et al, 2019 ; Sen et al, 2020 ; Yang et al, 2020 ; Yassin, 2020 ), in which the ORR was 91% (95% CI: 82–98%, I 2 = 12%, p = 0.34). In addition, eight studies reported the ORR of TDT patients after the treatment of thalidomide (ORR, 83%; 95% CI: 72–91%, I 2 = 51%, p = 0.05) ( Figure 2 ) ( Chen et al, 2017 ; Li et al, 2018 ; Nag et al, 2020 ; Sen et al, 2020 ; Yang et al, 2020 ; Yassin, 2020 ; Chen et al, 2021 ; Li et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…Seven studies reported the ORR of NTDT patients after the treatment of thalidomide ( Chen et al, 2017 ; Li et al, 2018 ; Ren et al, 2018 ; Jain et al, 2019 ; Sen et al, 2020 ; Yang et al, 2020 ; Yassin, 2020 ), in which the ORR was 91% (95% CI: 82–98%, I 2 = 12%, p = 0.34). In addition, eight studies reported the ORR of TDT patients after the treatment of thalidomide (ORR, 83%; 95% CI: 72–91%, I 2 = 51%, p = 0.05) ( Figure 2 ) ( Chen et al, 2017 ; Li et al, 2018 ; Nag et al, 2020 ; Sen et al, 2020 ; Yang et al, 2020 ; Yassin, 2020 ; Chen et al, 2021 ; Li et al, 2021 ). Compared with the placebo group, the thalidomide group had higher odds of ORR (odds ratio = 20.4; 95% CI: 6.75–61.64) ( Supplementary Figure S3 ) ( Chen et al, 2021 ).…”

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: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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“…47 Thalidomide has also been associated with hematologic responses in both NTDT and TDT patients in observational studies and small trials from India or China. [48][49][50][51][52][53][54][55] Polymorphisms in HBG2 and HBS1L-MYB contributed significantly to thalidomide response in these patients. 56 Larger clinical trials with thalidomide in TDT patients are ongoing in Pakistan (NCT03651102)…”

Section: Fetal Hemoglobin Inducing Agentsmentioning

confidence: 91%

2021 update on clinical trials in β‐thalassemia

Musallam¹,

Bou‐Fakhredin

Cappellini

et al. 2021

American J Hematol

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The treatment landscape for patients with β-thalassemia is witnessing a swift evolution, yet several unmet needs continue to persist. Patients with transfusiondependent β-thalassemia (TDT) primarily rely on regular transfusion and iron chelation therapy, which can be associated with considerable treatment burden and cost.Patients with non-transfusion-dependent β-thalassemia (NTDT) are also at risk of significant morbidity due to the underlying anemia and iron overload, but treatment options in this patient subgroup are limited. In this review, we provide updates on clinical trials of novel therapies targeting the underlying pathology in β-thalassemia, including the α/non-α-globin chain imbalance, ineffective erythropoiesis, and iron dysregulation. | INTRODUCTIONThe β-thalassemias are a group of inherited disorders of hemoglobin (Hb) synthesis characterized by chronic anemia of varying severity.The degree of anemia relies on several genetic and environmental factors and determines the need for regular transfusion therapy. It is now common practice to classify patients as having transfusion-The TDT patients (β-thalassemia major and severe forms of HbE/β-thalassemia) are those who commonly present in early childhood with severe anemia and require lifelong transfusion therapy for survival. 1 Although the introduction of transfusions improved survival in TDT patients, it did not come without its own side-effect, systemic iron overload leading to end-organ damage and increased mortality from cardiac or hepatic disease. [2][3][4] Advances in iron chelation therapy and the introduction of MRI techniques to detect organ-specific iron overload have led to improved management and patient outcomes. 5,6 Still, TDT comes with considerable burden to the patient, clinician, and overall healthcare system owing to persistent morbidity and high healthcare utilization, poor access to optimal care and high treatment cost especially in resource-limited countries, and several unmet needs in terms of efficacy, safety and adherence to conventional therapies. 7 Allogeneic hematopoietic stem-cell transplantation (HSCT) has been used successfully for the past few decades to offer curative therapy for patients with TDT, but is only available to a minority of patients with compatible donors. 1 Patients with NTDT (β-thalassemia intermedia and mildmoderate forms of HbE/β-thalassemia) usually present later in childhood or even in adolescence with mild-moderate anemia that does not require immediate placement on a regular transfusion program. 1,8 Progress made over the past few decades has indicated that the diagnosis of NTDT carries greater morbidity than previously recognized.Ineffective erythropoiesis and anemia have been linked to an array of morbidities stemming from chronic hypoxia and an established hypercoagulable state. 1 Patients with Hb levels < 10 g/dl are at an increased risk of morbidity development, and variations of 1 g/dl can change a patient's morbidity risk. 9,10 There are currently no approved agents for the management of anem...

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Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and In Silico Studies

Abdallah,

Eissa,

Mehany

et al. 2024

Chemistry & Biodiversity

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New thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7a and 28, and phthalazine based 20a against HepG‐2, MCF‐7, PC3, and HCT‐116 cell lines, compared to thalidomide. In particular, compound 20a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF‐α, IL‐6, caspase 3, COX‐I/II, and VEGFR‐2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF‐7 cells, the most sensitive cell line to the current new molecules. Compound 20a caused reduction in levels of TNF‐α and IL‐6 by 75.22% and 82.51%, respectively. It elevated the caspase‐3 level by 7.21‐fold. Furthermore, IC50 against COX‐I, COX‐II, and VEGFR‐2 were 0.65 μM, 0.33 μM, and 232 nM, respectively. In addition, it raised the apoptosis rate from 65.65% to 99.89%. Moreover, 20a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR‐2, along with computational ADME properties. This work suggests the high significance of compounds 20a, 7a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs.

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Thalidomide for Patients With Thalassemia Intermedia: A Retrospective Multicenter Clinical Study

Cited by 27 publications

References 27 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

2021 update on clinical trials in β‐thalassemia

Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and In Silico Studies

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