Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment

Abstract

Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy. The priority order of donor source for bone marrow transplantation is: (1) HLA-identical sibling, (2) HLA-matched unrelated donor, and (3) HLA-haploidentical donor if an HLA-matched unrelated donor is not rapidly available. Each of these donor marrow sources may be preferable to nontransplant IST. We make this recommendation because of the long-term persistent risk for disease relapse and secondary myelodysplastic syndrome or acute myeloid leukemia with the use of nontransplant IST for patients with aplastic anemia. In contrast, marrow transplantation is associated with high cure rates of aplastic anemia and a relatively low risk for graft-versus-host disease, with many patients now living for decades without the risk for disease recurrence or the development of clonal disorders. Implementation of this first-line treatment strategy will provide patients with severe aplastic anemia the best chance of long-term disease-free survival.

Comparable survival outcome between transplantation from haploidentical donor and matched related donor or unrelated donor for severe aplastic anemia patients aged 40 years and older: A retrospective multicenter cohort study

“…This risk also seemed to increase with aging . So hematologists tended to pursue a better FFS, and it was recommended that HSCT was preferable to IST no matter the donor was HLA‐matched or haploidentical . Our previous study also showed a trend of higher FFS in patients older than 40 years of age in 8th year after HID‐HSCT compared with those only received IST .…”

“…Hematopoietic stem cell transplantation (HSCT) has been generally accepted as the only method able to cure severe aplastic anemia (SAA). According to the current algorithm, HSCT was recommended as upfront therapy for young patients with a matched donor . Considering the high transplantation‐related mortality (TRM) rate, priority was given to immune suppression treatment (IST) in patients older than 40 years.…”

“…However, this practice might predispose patients to prolonged neutropenia, a higher risk of lethal hemorrhage and a heavier iron burden. Moreover, concerns about relapse and clonal evolution after IST might also prompt clinicians to choose HSCT, particularly in cases of very severe aplastic anemia (vSAA) . With the advantages of easy donor availability and short preparation time for transplantation, HID‐HSCT was regarded as a potential and promising therapy for patients without MSD and URD.…”

“…According to the current algorithm, HSCT was recommended as upfront therapy for young patients with a matched donor. [1][2][3][4][5] Considering the high transplantation-related mortality (TRM) rate, priority was given to immune suppression treatment (IST) in patients older than 40 years. The outcome of HSCT in this age group was unsatisfactory, with long-term survival ranging from 49% to 65%, 3,6 and HSCT did not demonstrate an advantage over IST.…”

Allogeneic Bone Marrow Transplants for Pediatric Severe Aplastic Anemia: Real‐world Data comparing Matched Related and Unrelated Donors in a Developing Country. Retrospective study on behalf of the Pediatric Hematopoietic Stem Cell Transplant Working Group of the Brazilian Bone Marrow Transplantation Society (SBTMO) and the Brazil‐Seattle Consortium (Gedeco)

“…Other authors have reported equivalent OS between MRD and URD transplants in this patient population . While the 4‐year OS of 69% for our URD BMT patients is closer to that reported in other international studies, the 4‐year OS of 81% for the MRD BMT cases is lower than the 90%‐100% range reported in others countries and by international registries …”