Tags

Type your tag names separated by a space and hit enter

The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia.
Biol Blood Marrow Transplant. 2019 09; 25(9):e277-e284.BB

Abstract

The improved success of HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA) in recent decades has had an impact on the indications for and timing of this treatment modality. In the absence of a matched sibling donor (MSD), historically MUD HSCT was reserved as an option after failure to respond to at least 2 courses of immunosuppressive therapy (IST) in adults with SAA, but with improved outcomes over time, it is now considered following failure to respond to 1 course of IST. Recent national and international studies and guidelines now recommend upfront MUD HSCT as an option for children for whom an MUD is readily available, because outcomes are similar to those for MSD HSCT. Fludarabine-based conditioning and the use of in vivo T cell depletion with antithymocyte globulin or alemtuzumab has been associated with a reported overall survival (OS) of >85% in adult patients undergoing MUD HSCT. However, the recent introduction of eltrombopag for patients with SAA has transformed the treatment landscape, and there is currently much interest in its use with IST as upfront treatment, which showed a high response rate in an early-phase study. The risks of HSCT, especially graft-versus-host disease (GVHD), need to be carefully balanced against the concerns of IST, namely relapse and later clonal evolution to myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). In the absence of a current prospective randomized trial comparing these 2 approaches, in this review we examine the evidence supporting consideration of early MUD HSCT in adults with SAA who would have been considered for MSD HSCT but who lack a MSD and for whom an MUD is readily available, especially using an irradiation-free conditioning regimen, with a low risk of GVHD, as another treatment option. This option may be offered to patients to provide them with an informed choice, with the aim of curing disease rather than achieving freedom from disease, relapse-free survival, or OS. Furthermore, understanding the immune signature for the response to IST and the immunologic responses to somatic mutations and clonal progression to MDS/AML may help define the future indications for upfront HSCT and a more precise medical approach to therapy.

Authors+Show Affiliations

Department of Haematological Medicine, King's College Hospital/King's College London, London, UK. Electronic address: judith.marsh@nhs.net.Federico II University of Naples, Naples, Italy.Department of Haematological Medicine, King's College Hospital/King's College London, London, UK.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

31129354

Citation

Marsh, Judith C W., et al. "The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 25, no. 9, 2019, pp. e277-e284.
Marsh JCW, Risitano AM, Mufti GJ. The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia. Biol Blood Marrow Transplant. 2019;25(9):e277-e284.
Marsh, J. C. W., Risitano, A. M., & Mufti, G. J. (2019). The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 25(9), e277-e284. https://doi.org/10.1016/j.bbmt.2019.05.012
Marsh JCW, Risitano AM, Mufti GJ. The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia. Biol Blood Marrow Transplant. 2019;25(9):e277-e284. PubMed PMID: 31129354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia. AU - Marsh,Judith C W, AU - Risitano,Antonio M, AU - Mufti,Ghulam J, Y1 - 2019/05/24/ PY - 2019/03/29/received PY - 2019/05/07/revised PY - 2019/05/16/accepted PY - 2019/5/28/pubmed PY - 2020/7/30/medline PY - 2019/5/27/entrez KW - Alemtuzumab KW - Hematopoietic stem cell transplantation KW - Severe aplastic anemia SP - e277 EP - e284 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 25 IS - 9 N2 - The improved success of HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for severe aplastic anemia (SAA) in recent decades has had an impact on the indications for and timing of this treatment modality. In the absence of a matched sibling donor (MSD), historically MUD HSCT was reserved as an option after failure to respond to at least 2 courses of immunosuppressive therapy (IST) in adults with SAA, but with improved outcomes over time, it is now considered following failure to respond to 1 course of IST. Recent national and international studies and guidelines now recommend upfront MUD HSCT as an option for children for whom an MUD is readily available, because outcomes are similar to those for MSD HSCT. Fludarabine-based conditioning and the use of in vivo T cell depletion with antithymocyte globulin or alemtuzumab has been associated with a reported overall survival (OS) of >85% in adult patients undergoing MUD HSCT. However, the recent introduction of eltrombopag for patients with SAA has transformed the treatment landscape, and there is currently much interest in its use with IST as upfront treatment, which showed a high response rate in an early-phase study. The risks of HSCT, especially graft-versus-host disease (GVHD), need to be carefully balanced against the concerns of IST, namely relapse and later clonal evolution to myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). In the absence of a current prospective randomized trial comparing these 2 approaches, in this review we examine the evidence supporting consideration of early MUD HSCT in adults with SAA who would have been considered for MSD HSCT but who lack a MSD and for whom an MUD is readily available, especially using an irradiation-free conditioning regimen, with a low risk of GVHD, as another treatment option. This option may be offered to patients to provide them with an informed choice, with the aim of curing disease rather than achieving freedom from disease, relapse-free survival, or OS. Furthermore, understanding the immune signature for the response to IST and the immunologic responses to somatic mutations and clonal progression to MDS/AML may help define the future indications for upfront HSCT and a more precise medical approach to therapy. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/31129354/The_Case_for_Upfront_HLA_Matched_Unrelated_Donor_Hematopoietic_Stem_Cell_Transplantation_as_a_Curative_Option_for_Adult_Acquired_Severe_Aplastic_Anemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(19)30323-4 DB - PRIME DP - Unbound Medicine ER -