The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults

Agnieszka Piekarska; Katarzyna Pawelec; Anna Szmigielska-Kapłon; Marek Ussowicz

doi:10.3389/fimmu.2024.1378432

The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults

Front Immunol. 2024 Apr 5:15:1378432. doi: 10.3389/fimmu.2024.1378432. eCollection 2024.

Authors

Agnieszka Piekarska¹, Katarzyna Pawelec², Anna Szmigielska-Kapłon³, Marek Ussowicz⁴

Affiliations

¹ Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland.
² Department of Oncology, Pediatric Hematology, Clinical Transplantology and Pediatrics, Medical University of Warsaw, Warsaw, Poland.
³ Department of Hematology, Medical University of Lodz, Lodz, Poland.
⁴ Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Wroclaw, Poland.

Abstract

Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell-mediated autoimmune attack against hematopoietic stem cells. The key diagnostic challenge in children, but also in adults, is to exclude the possible underlying congenital condition and myelodysplasia. The choice of treatment options, either allogeneic hematopoietic cell transplantation (alloHCT) or immunosuppressive therapy (IST), depends on the patient's age, comorbidities, and access to a suitable donor and effective therapeutic agents. Since 2022, horse antithymocyte globulin (hATG) has been available again in Europe and is recommended for IST as a more effective option than rabbit ATG. Therefore, an update on immunosuppressive strategies is warranted. Despite an improved response to the new immunosuppression protocols with hATG and eltrombopag, some patients are not cured or remain at risk of aplasia relapse or clonal evolution and require postponed alloHCT. The transplantation field has evolved, becoming safer and more accessible. Upfront alloHCT from unrelated donors is becoming a tempting option. With the use of posttransplant cyclophosphamide, haploidentical HCT offers promising outcomes also in AA. In this paper, we present the state of the art in the management of severe AA for pediatric and adult patients based on the available guidelines and recently published studies.

Keywords: antithymocyte globulin; aplastic anemia; eltrombopag; hATG; hematopoietic cell transplantation; immunosuppression; rATG.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anemia, Aplastic* / immunology
Anemia, Aplastic* / therapy
Animals
Antilymphocyte Serum / therapeutic use
Child
Hematopoietic Stem Cell Transplantation* / adverse effects
Hematopoietic Stem Cell Transplantation* / methods
Humans
Immunosuppressive Agents / therapeutic use
Immunotherapy / methods
Treatment Outcome

Substances

Antilymphocyte Serum
Immunosuppressive Agents

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study received funding from Pfizer. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. All authors declare no other competing interests.