Diagnostik und Therapie der alpha- und beta-Thalassämien

Die komplexe Behandlung von Patienten mit Thalassämien stellt nicht nur eine medizinische, sondern angesichts der in den letzten Jahren deutlich gestiegenen Patientenzahlen auch eine gesellschaftliche Herausforderung dar, die eine sehr enge Zusammenarbeit aller Behandler erfordert. Der vorliegende Beitrag erläutert Ursachen und Pathogenese der alpha- und beta-Thalassämien und bietet eine Übersicht zu Klinik und Therapien.

Abstract

Thalassemias are a heterogeneous group of genetic diseases based on a quantitative disorder of globin chain synthesis. They are among the most frequent monogenic hereditary diseases worldwide. Migration during recent years led to a profoundly increasing number of patients in countries where the indigenous population has not been affected. The complex treatment of the patients represents a medical and socioeconomic challenge with the need for structured interdisciplinary clinical care and close collaboration among healthcare providers, regulatory authorities, and health care insurance companies. The following article provides an overview of the causes, pathogenesis, clinical presentation, and treatment of alpha- and beta-thalassemias.

Schlüsselwörter

Hämoglobinopathie - α-Thalassämie - β-Thalassämie - Eisenüberladung - Hämochromatose - Chelat-Therapie

Key worsd

Hemoglobinopathy - α-thalassemia - β-thalassemia - iron overload - hemochromatosis, chelation

Publication History

Article published online:
20 September 2022

• Literatur

• 1 Cario H. Hemoglobinopathies – genetically diverse, clinically complex, and globally relevant. Memo – Mag Eur Med Oncol 2018; 11: 235-240
• 2 Giardine B, Borg J, Viennas E. Updates of the HbVar database of human hemoglobin variants and thalassemia mutations. Nucleic Acids Res 2014; 42: D1063-D1069
• 3 Piel FB, Weatherall DJ. The alpha-thalassemias. N Engl J Med 2014; 371: 1908-1916
• 4 Taher AT, Musallam KM, Cappellini MD. β-Thalassemias. N Engl J Med 2021; 384: 727-743
• 5 Harteveld CL, Higgs DR. Alpha-thalassaemia. Orphanet J Rare Dis 2010; 5: 13
• 6 Horvei P, MacKenzie T, Kharbanda S. Advances in the management of α-thalassemia major: reasons to be optimistic. Hematology/the Education Program of the American Society of Hematology 2021: 592-599
• 7 Songdej D, Babbs C, Higgs DR. An international registry of survivors with Hb Bart’s hydrops fetalis syndrome. Blood 2017; 129: 1251-1259
• 8 Amid A, Chen S, Brien W. et al. Optimizing chronic transfusion therapy for survivors of hemoglobin Barts hydrops fetalis. Blood 2016; 127: 1208-1211
• 9 Cario H, Grosse R, Jarisch A. et al S2k-Leitlinie: Diagnostik und Therapie der sekundären Eisenüberladung bei Patienten mit angeborenen Anämien. AWMF online 2022. Im Internet (Stand: 25.03.2022): www.awmf.org/leitlinien/detail/ll/025-029.html
• 10 Cario H, Hoferer A, Schmugge Liner M. et al Beta-Thalassämie. Onkopedia-Leitlinien 2019. Im Internet (Stand: 25.03.2022): www.onkopedia.com/de/onkopedia/guidelines/beta-thalassaemie/@@guideline/html/index.html
• 11 Premawardhena A, Arambepola M, Katugaha N. et al. Is the beta thalassaemia trait of clinical importance?. Br J Haematol 2008; 141: 407-410
• 12 Taher AT, Musallam KM, Cappellini MD. et al. Optimal management of beta thalassaemia intermedia. Br J Haematol 2011; 152: 512-523
• 13 Musallam KM, Cappellini MD, Taher AT. Variations in hemoglobin level and morbidity burden in non-transfusion-dependent β-thalassemia. Ann Hematol 2021; 100: 1903-1905
• 14 Musallam KM, Taher AT, Cappellini MD. et al. Clinical experience with fetal hemoglobin induction therapy in patients with beta-thalassemia. Blood 2013; 121: 2199-2212
• 15 Cappellini MD, Viprakasit V, Taher AT. et al. A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia. N Engl J Med 2020; 382: 1219-1231
• 16 Musallam KM, Bou-Fakhredin R, Cappellini MD. et al. 2021 update on clinical trials in β-thalassemia. Am J Hematol 2021; 96: 1518-1531
• 17 Baronciani D, Boumendil A, Dalissier A. et al. Hematopoietic Cell Transplantation in Thalassemia and Sickle Cell Disease: Report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry: 2000-2017. Blood 2018; 132: 168
• 18 Kunz JB, Kulozik AE. Gene Therapy of the Hemoglobinopathies. HemaSphere 2020; 4: e479
• 19 Locatelli F, Thompson AA, Kwiatkowski JL. et al. Betibeglogene Autotemcel Gene Therapy for Non-β(0)/β(0) Genotype β-Thalassemia. N Engl J Med 2022; 386: 415-427
• 20 Frangoul H, Altshuler D, Cappellini MD. et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. N Engl J Med 2021; 384: 252-260