Immunosuppressive Therapy for Aplastic Anemia

Marsh, Judith; Gandhi, Shreyans; Mufti, Ghulam J.

doi:10.1016/b978-0-12-804152-9.00006-3

Cited by 1 publication

(1 citation statement)

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“…Allogeneic HSCT subsequently became the gold standard first-line treatment for patients with SAA with an MSD. Concurrently, antithymocyte globulin (ATG), with or without androgens, was being developed as an alternative therapeutic option for patients with SAA who lacked an MSD or who were ineligible for HSCT due to older age or the presence of nonsevere AA, resulting in similar OS as seen with MSD HSCT [10]. In a German prospective randomized study, the introduction of cyclosporine A (CSA) for use in combination with ATG significantly increased the response rate to 65%, compared with 35% with ATG alone [5,11].…”

Section: Current Indication For Hla-matched Unrelated Donor Hematopoimentioning

confidence: 99%

The Case for Upfront HLA-Matched Unrelated Donor Hematopoietic Stem Cell Transplantation as a Curative Option for Adult Acquired Severe Aplastic Anemia

Marsh

Risitano

Mufti

2019

Biology of Blood and Marrow Transplantation

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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.

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Section: Current Indication For Hla-matched Unrelated Donor Hematopoimentioning

confidence: 99%