Abstract

Review Article

Treatment Options for Congenital Dyserythropoietic Anemias (CDAs): Advances in Bone Marrow Transplantation, Gene Therapy, and Targeted Therapies

Sophia Delicou*, Maria Moraki, Elena Papatheodorou and Aikaterini Xydaki

Published: 30 November, 2024 | Volume 8 - Issue 1 | Pages: 027-033

Congenital Dyserythropoietic Anaemia (CDA) is a rare genetic disorder that affects the maturation of red blood cells. The disorder is classified into different types, with a prevalence ranging from 1 in 100,000 to 1 in 1,000,000 individuals. Treatment strategies are designed with the primary focus on symptom management, the prevention and treatment of complications, and the underlying disease pathophysiology. The advent of bone marrow transplantation, gene therapy, and targeted therapies has considerably expanded the scope for therapeutic intervention in CDAs. Supportive care, including blood transfusions and iron chelation therapy, has demonstrated efficacy in managing iron overload and improving overall survival rates. The potential of gene therapy, targeted therapies, and hematopoietic growth factors in the treatment of CDA is currently being investigated. Further research and clinical trials are required to develop more effective and personalized therapeutic interventions.

Read Full Article HTML DOI: 10.29328/journal.jhcr.1001031 Cite this Article Read Full Article PDF

Keywords:

Personalized interventions, Congenital Dyserythropoietic Anaemia (CDA), Red blood cell maturation, Targeted therapies

References

  1. Gambale A, Iolascon A, Andolfo I, Russo R. Diagnosis and management of congenital dyserythropoietic anemias. Expert review of hematology. 2016;9(3):283-296. Available from: https://doi.org/10.1586/17474086.2016.1131608
  2. Russo R, Iolascon A, Andolfo I, Marra R, Rosato BE. Updates on clinical and laboratory aspects of hereditary dyserythropoietic anemias. International Journal of Laboratory Hematology. 2024. Available from: https://doi.org/10.1111/ijlh.14307
  3. Iolascon A, Esposito MR, Russo R. Clinical aspects and pathogenesis of congenital dyserythropoietic anemias: from morphology to molecular approach. haematologica. 2012;97(12):1786. Available from: https://doi.org/10.3324/haematol.2012.072207
  4. Renella R, Wood WG. The congenital dyserythropoietic anemias. Hematology/Oncology Clinics. 2009;23(2):283-306. Available from: https://doi.org/10.1016/j.hoc.2009.01.010
  5. Cazzola M. Ineffective erythropoiesis and its treatment. Blood, The Journal of the American Society of Hematology. 2022;139(16):2460-2470. Available from:https://doi.org/10.1182/blood.2021011045
  6. Cappellini MD. Exjade®(deferasirox, ICL670) in the treatment of chronic iron overload associated with blood transfusion. Therapeutics and clinical risk management. 2007;3(2):291-299. Available from: https://doi.org/10.2147/tcrm.2007.3.2.291
  7. Coates TD. Iron overload in transfusion-dependent patients. Hematology 2014, the American Society of Hematology Education Program Book. 2019;2019(1):337-344. Available from: https://doi.org/10.1182/hematology.2019000036
  8. Wanless IR, Sweeney G, Dhillon AP, Guido M, Piga A, Galanello R, et al. Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia. Blood, the Journal of the American Society of Hematology. 2002;100(5):1566-1569. Available from: https://doi.org/10.1182/blood-2002-01-0306
  9. Maggio A. Light and shadows in the iron chelation treatment of haematological diseases. British journal of haematology. 2007;138(4):407-421. Available from: https://doi.org/10.1111/j.1365-2141.2007.06666.x
  10. Uygun V, Russo R, Karasu G, Daloğlu H, Iolascon A, Yeşilipek A. Hematopoietic stem cell transplantation in congenital dyserythropetic anemia type II: a case report and review of the literature. Journal of Pediatric Hematology/Oncology. 2020;42(6):e507-510. Available from: https://doi.org/10.1097/mph.0000000000001612
  11. Braun M, Wölfl M, Wiegering V, Winkler B, Ertan K, Bald R, et al. Successful treatment of an infant with CDA type II by intrauterine transfusions and postnatal stem cell transplantation. Pediatric Blood & Cancer. 2014;61(4):743-745. Available from: https://doi.org/10.1002/pbc.24786
  12. Gupta V, Braun TM, Chowdhury M, Tewari M, Choi SW. A systematic review of machine learning techniques in hematopoietic stem cell transplantation (HSCT). Sensors. 2020;20(21):6100. Available from: https://doi.org/10.3390/s20216100
  13. Rangarajan HG, Stanek JR, Abdel-Azim H, Modi A, Haight A, McKinney CM, et al. Hematopoietic cell transplantation for congenital dyserythropoietic anemia: a report from the pediatric transplant and cellular therapy Consortium. Transplantation and Cellular Therapy. 2022;28(6):329-e1. Available from: https://doi.org/10.1016/j.jtct.2022.03.007
  14. Miano M, Eikema DJ, Aljurf M, van’t Veer PJ, Öztürk G, Wölfl M, et al. Stem cell transplantation for congenital dyserythropoietic anemia: an analysis from the European Society for Blood and Marrow Transplantation. haematologica. 2019;104(8):e335. Available from: https://doi.org/10.3324/haematol.2018.206623
  15. Sayed N, Allawadhi P, Khurana A, Singh V, Navik U, Pasumarthi SK, et al. Gene therapy: Comprehensive overview and therapeutic applications. Life sciences. 2022;294:120375. Available from: https://doi.org/10.1016/j.lfs.2022.120375
  16. Dessy-Rodriguez M, Fañanas-Baquero S, Venturi V, Payán-Pernía S, Tornador C, Hernandez G, et al. Modelling Congenital Dyserythropoietic Anemia Type II through Gene Editing in Hematopoietic Stem and Progenitor Cells. Blood. 2020;136:27. Available from: https://doi.org/10.1182/blood-2020-139207
  17. Kumari R, Kaźmierczak P. Modeling congenital dyserythropoietic anemia in genetically modified mice. Acta Haematologica Polonica. 2022;53(1):26-38. Available from: https://doi.org/10.5603/AHP.a2022.0003
  18. Khoriaty R, Weyand A, Hesketh G, Bernard A, Everett L, Zhu G, et al. Overlap of SEC23A and SEC23B function suggests a novel therapeutic approach for congenital dyserythropoietic anemia type II. Blood. 2017;130:80. Available from: http://dx.doi.org/10.1182/blood.V130.Suppl_1.80.80
  19. Chen Y, Wen R, Yang Z, Chen Z. Genome editing using CRISPR/Cas9 to treat hereditary hematological disorders. Gene Therapy. 2022;29(5):207-216. Available from: https://doi.org/10.1038/s41434-021-00247-9
  20. Dessy-Rodriguez M, Fañanas-Baquero S, Venturi V, Payan S, Tornador C, Hernández G, et al. Lentiviral Gene Therapy for the Correction of Congenital Dyserythropoietic Anemia Type II. Blood. 2021;138:1994. Available from: http://dx.doi.org/10.1182/blood-2021-152332
  21. Rahimmanesh I, Boshtam M, Kouhpayeh S, Khanahmad H, Dabiri A, Ahangarzadeh S, et al. Gene editing-based technologies for beta-hemoglobinopathies treatment. Biology. 2022;11(6):862. Available from: https://doi.org/10.3390/biology11060862
  22. Srole DN, Ganz T. Erythroferrone structure, function, and physiology: Iron homeostasis and beyond. Journal of cellular physiology. 2021;236(7):4888-4901. Available from: https://doi.org/10.1002/jcp.30247
  23. Babitt JL. Erythroferrone in iron regulation and beyond. Blood, The Journal of the American Society of Hematology. 2022;139(3):319-321. Available from: https://doi.org/10.1182/blood.2021014326
  24. Koury MJ. Erythroferrone: a missing link in iron regulation. The Hematologist. 2015;12(1).
  25. Babar S, Saboor M. Erythroferrone in focus: emerging perspectives in iron metabolism and hematopathologies. Blood Science. 2024;6(4):e00198. Available from: https://doi.org/10.1097/bs9.0000000000000198
  26. van Vuren AJ, Eisenga MF, van Straaten S, Glenthøj A, Gaillard CA, Bakker SJ, et al. Interplay of erythropoietin, fibroblast growth factor 23, and erythroferrone in patients with hereditary hemolytic anemia. Blood advances. 2020;4(8):1678-1682. Available from: https://doi.org/10.1182/bloodadvances.2020001595
  27. De Rosa G, Andolfo I, Marra R, Manna F, Rosato BE, Iolascon A, et al. RAP-011 rescues the disease phenotype in a cellular model of congenital dyserythropoietic anemia type II by inhibiting the SMAD2-3 pathway. International journal of molecular sciences. 2020;21(15):5577. Available from: https://doi.org/10.3390/ijms21155577
  28. Lan Z, Lv Z, Zuo W, Xiao Y. From bench to bedside: The promise of sotatercept in hematologic disorders. Biomedicine & Pharmacotherapy. 2023;165:115239. Available from: https://doi.org/10.1016/j.biopha.2023.115239
  29. Davies AT, Devlin PM, Dugan C, Richards T, Miles LF. Non‐erythropoiesis stimulating agent, non‐iron therapies for the management of anemia: A scoping review. Transfusion. 2023;63(4):849-860. Available from: https://doi.org/10.1111/trf.17274
  30. Iolascon A, Rivella S, Anagnou NP, Camaschella C, Swinkels D, Muckenthaler MU, Porto G, Barcellini W, Andolfo I, Risitano AM, Kattamis A. The EHA research roadmap: anemias. Hemasphere. 2021;5(7):e607. Available from: https://doi.org/10.1097/hs9.0000000000000607
  31. Kubasch AS, Fenaux P, Platzbecker U. Development of luspatercept to treat ineffective erythropoiesis. Blood advances. 2021;5(5):1565-1575. Available from: https://doi.org/10.1182/bloodadvances.2020002177
  32. Lee D, Kim DW, Cho JY. Role of growth factors in hematopoietic stem cell niche. Cell biology and toxicology. 2020;36(2):131-144. Available from: https://doi.org/10.1007/s10565-019-09510-7
  33. Mann Z, Sengar M, Verma YK, Rajalingam R, Raghav PK. Hematopoietic stem cell factors: their functional role in self-renewal and clinical aspects. Frontiers in Cell and Developmental Biology. 2022;10:664261. Available from: https://doi.org/10.3389/fcell.2022.664261
  34. Cappellini MD, Marcon A, Fattizzo B, Motta I. Innovative treatments for rare anemias. HemaSphere. 2021 Jun 1;5(6):e576. Available from: https://doi.org/10.1097/hs9.0000000000000576
  35. Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014;20(4):408-414. Available from: https://doi.org/10.1038/nm.3512
  36. Carrancio S, Markovics J, Wong P, Leisten J, Castiglioni P, Groza MC, et al. An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin. Br J Haematol. 2014;165(6):870-882. Available from: https://doi.org/10.1111/bjh.12838

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