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Experience with combination of hydroxyurea and low-dose thalidomide in transfusion-dependent beta thalassemia patients

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Abstract

Hydroxyurea (HU) and thalidomide have been reported to improve clinical and hematological parameters in transfusion-dependent beta thalassemia (TDT). Therefore, we retrospectively analyzed the combination of HU and thalidomide in 140 transplant ineligible TDT, ≥ 10 years old, visiting our thalassemia clinic between October 2014 and November 2019. Responses were defined as maintenance of hemoglobin ≥9gm/dl without transfusion as complete response (CR) and with at least 50% reduction in transfusion burden as partial response (PR). Patients with less than 50% transfusion burden reduction for consecutive 6 months of therapy were defined as non-responders (NR), and treatment was discontinued thereafter. Primary end point was overall response rate (ORR) at last follow-up. At median follow-up of 22.6 (95% CI 16.4–28.7) months, 76 (57.2%) patients achieved CR and 19 (14.3%) achieved PR, accounting to an ORR of 71.5%. Among responders at last follow-up, a significant increase in the post-treatment hemoglobin (0.88±0.37gm/dl, p<0.0001) and drop in serum ferritin (−1490.5ng/ml, p<0.0001) were observed. Median time to CR was 124 (95% CI 75.3–172.6) days. Median longest continuous CR was 791 (95% CI 662.2–919.7) days. Common toxicities observed were sedation (25%), hyperbilirubinemia {(23.57%, grade 3/4 =17 (12.14%)}, and constipation (22.8%). Nearly three-fourth of the patients has responded with majority having CR. Adverse events are a concern; hence, regular close monitoring is a prerequisite.

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Acknowledgements

We would like to acknowledge Dr Priyanka Soni in initial data collection. We are indebted to Dr Anurag Sharma, Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India, for providing the guidance in the statistical assessment. We also like to acknowledge all the staff of Department of Hematology and BMT unit, Rajiv Gandhi Cancer Institute and Research Centre, for providing the support in conducting the study.

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Authors and Affiliations

  1. Department of Hematology and Bone Marrow Transplant Unit, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, Delhi, 110085, India

    Dinesh Bhurani, Jyotsna Kapoor, Neha Yadav, Vishvdeep Khushoo, Narendra Agrawal, Rayaz Ahmed & Pallavi Mehta

  2. National Thalassemia Welfare Society, Delhi, 110018, India

    Jatinder Singh Arora

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  1. Dinesh Bhurani
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  2. Jyotsna Kapoor
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DB conceptualized, interpreted, and contributed in writing the manuscript. JK collected, analyzed, and interpreted the data and contributed in writing the manuscript. NY collected the data. PM interpreted the data and was a major contributor in writing the manuscript. All authors read and approved the manuscript.

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Correspondence to Dinesh Bhurani.

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All authors stated that the study has been approved by the appropriate institutional review board and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Since this is a retrospective study, hence no formal informed consent is required.

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Bhurani, D., Kapoor, J., Yadav, N. et al. Experience with combination of hydroxyurea and low-dose thalidomide in transfusion-dependent beta thalassemia patients. Ann Hematol 100, 1417–1427 (2021). https://doi.org/10.1007/s00277-021-04501-3

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  • DOI: https://doi.org/10.1007/s00277-021-04501-3

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