Diagnostik und Therapie der aplastischen Anämie – Update 2021

Was ist neu?

Diagnostik Telomeropathie-Erkrankungen und andere konstitutionelle Ursachen werden zunehmend auch im Erwachsenenalter als AA-Ursache erkannt. Screening-Untersuchungen, Erfassung der Familiengeschichte und körperliche Untersuchung auf mögliche Hinweise konstitutioneller Syndrome sind daher auch bei erwachsenen AA-Patienten durchzuführen.

Therapie Eine Stammzelltransplantation von unverwandten 10/10-Spendern ergibt fast ebenso gute Ergebnisse wie von Familienspendern bei Patienten unter 30. Eltrombopag ist zur Behandlung von refraktären Patienten mit schwerer aplastischer Anämie zugelassen. Patienten mit Chromosom-7-Anomalien sollen kein Eltrombopag erhalten; vor Eltrombopag-Therapie muss ein zytogenetisches Screening erfolgen. Patienten mit seltenen Erkrankungen wie der AA sollte die Anbindung an Patientenselbsthilfegruppen empfohlen werden und die Lebensqualität muss bei allen Therapieformen adäquat erfasst und gewürdigt werden.

Ausblick Eine immunsuppressive Therapie mit ATG und CSA wird zukünftig mit Eltrombopag kombiniert werden. Romiplostim, ein weiterer TRA, ist ebenfalls wirksam bei AA. Die differenzierte molekulare Diagnostik wird die Pathophysiologie klonaler Evolution weiter verstehbar machen.

Abstract

The landscape of aplastic anemia (AA) is changing as new therapeutic options become available and sophistic diagnostics enable us to decipher various subgroups of bone marrow failure syndromes (BMFS) such as telomeropathies and other constitutional diseases with manifestations beyond childhood.

This article briefly summarizes developments of the last few years with potential clinical impact and puts it into perspective. Focus is given to the growing list of inherited BMFS and the need to e. g. screen patients at all ages for telomeropathies before initiation of treatment as part of routine evaluation of AA. The usage of next generation sequencing (NGS) to differentiate between AA and malignancies such as myelodysplatic syndrome (MDS) and the need to watch out for potential clonal evolution during and after treatment is also briefly discussed. Recent data on combinations of immunosuppressive therapy (IST) with thrombopoietin receptor agonists (TRA) for patients with severe AA as well as newer data with TRA mono-therapy for patients with moderate AA are presented. Finally the importance of supportive measures, structures and quality of life aspects are highlighted.

Schlüsselwörter

aplastische Anämie - Telomeropathie - Thrombopoetin-Rezeptor-Agonisten - Lebensqualität - klonale Evolution

Key words

aplastic anemia - telomeropathies - thrombopoietin receptor agonists - quality of life - clonal evolution

Publication History

Article published online:
29 March 2021

• Literatur

• 1 Young NS. Aplastic Anemia. N Engl J Med 2018; 379: 1643-1656 . doi:10.1056/NEJMra1413485
• 2 Bacigalupo A, Oneto R, Schrezenmeier H. et al First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001-2012. Am J Hematol 2018; 93: 643-648 . doi:10.1002/ajh.25081
• 3 Ferreira MSV, Kirschner M, Halfmeyer I. et al Comparison of flow-FISH and MM-qPCR telomere length assessment techniques for the screening of telomeropathies. Ann N Y Acad Sci 2020; 1466: 93-103 . doi:10.1111/nyas.14248
• 4 West AH, Churpek JE. Old and new tools in the clinical diagnosis of inherited bone marrow failure syndromes. Hematology/the Education Program of the American Society of Hematology American Society of Hematology Education Program 2017. 2017; 79-87 DOI: 10.1182/asheducation-2017.1.79.
• 5 Durrani J, Maciejewski JP. Idiopathic aplastic anemia vs hypocellular myelodysplastic syndrome. Hematology / the Education Program of the American Society of Hematology American Society of Hematology Education Program 2019. 2019; 97-104 DOI: 10.1182/hematology.2019000019.
• 6 Cooper JN, Young NS. Clonality in context: hematopoietic clones in their marrow environment. Blood 2017; 130: 2363-2372 . doi:10.1182/blood-2017-07-794362
• 7 Zheng G, Chen P, Pallavajjalla A. et al The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia. Am J Hematol 2019; 94: 1141-1148 . doi:10.1002/ajh.25592
• 8 Negoro E, Nagata Y, Clemente MJ. et al Origins of myelodysplastic syndromes after aplastic anemia. Blood 2017; 130: 1953-1957 . doi:10.1182/blood-2017-02-767731
• 9 Giammarco S, Peffault de Latour R, Sica S. et al Transplant outcome for patients with acquired aplastic anemia over the age of 40: has the outcome improved?. Blood 2018; 131: 1989-1992 . doi:10.1182/blood-2017-09-807859
• 10 Scheinberg P, Nunez O, Weinstein B. et al Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med 2011; 365: 430-438 . doi:10.1056/NEJMoa1103975
• 11 Cle DV, Atta EH, Dias DSP. et al Rabbit antithymocyte globulin dose does not affect response or survival as first-line therapy for acquired aplastic anemia: a multicenter retrospective study. Annals of hematology 2018; 97: 2039-2046 . doi:10.1007/s00277-018-3416-4
• 12 Bacigalupo A. Antithymocyte globulin and cyclosporin: standard of care also for older patients with aplastic anemia. Haematologica 2019; 104: 215-216 . doi:10.3324/haematol.2018.207167
• 13 Winkler T, Fan X, Cooper J. et al Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood 2019; 133: 2575-2585 . doi:10.1182/blood.2019000478
• 14 Scheinberg P. Activity of eltrombopag in severe aplastic anemia. Blood Adv 2018; 2: 3054-3062 . doi:10.1182/bloodadvances.2018020248
• 15 Ecsedi M, Lengline E, Knol-Bout C. et al Use of eltrombopag in aplastic anemia in Europe. Annals of hematology 2019; 98: 1341-1350 . doi:10.1007/s00277-019-03652-8
• 16 Alvarado LJ, Huntsman HD, Cheng H. et al Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-gamma. Blood 2019; 133: 2043-2055 . doi:10.1182/blood-2018-11-884486
• 17 Townsley DM, Dumitriu B, Liu D. et al Danazol Treatment for Telomere Diseases. N Engl J Med 2016; 374: 1922-1931 . doi:10.1056/NEJMoa1515319
• 18 Niedeggen C, Singer S, Groth M. et al Design and development of a disease-specific quality of life tool for patients with aplastic anaemia and/or paroxysmal nocturnal haemoglobinuria (QLQ-AA/PNH)-a report on phase III. Annals of hematology 2019; 98: 1547-1559 . doi:10.1007/s00277-019-03681-3
• 19 Townsley DM, Scheinberg P, Winkler T. et al Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med 2017; 376: 1540-1550 . doi:10.1056/NEJMoa1613878
• 20 Lee JW, Lee SE, Jung CW. et al Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial. The Lancet Haematology 2019; 6: e562-e572 . doi:10.1016/S2352-3026(19)30153-X
• 21 Hosokawa K, Yamazaki H, Tanabe M. et al. High-dose romiplostim accelerates hematologic recovery in patients with aplastic anemia refractory to eltrombopag. Leukemia 2020; DOI: 10.1038/s41375-020-0950-6.
• 22 Fan X, Desmond R, Winkler T. et al Eltrombopag for patients with moderate aplastic anemia or uni-lineage cytopenias. Blood Adv 2020; 4: 1700-1710 . doi:10.1182/bloodadvances.2020001657