Long-term outcome after bone marrow transplantation for severe aplastic anemia

Abstract

, 133 patients with severe aplastic anemia (SAA) underwent non-T cell-depleted allogeneic bone marrow transplantation from an HLA-identical sibling donor, at the Hospital Saint Louis using either the combination of cyclophosphamide (Cy) and thoracoabdominal irradiation (TAI; n ‫؍‬ 100) or Cy and antithymocyte globulin (ATG; n ‫؍‬ 33), as a conditioning regimen. With 13.6 years of follow-up, the 10-year survival estimate was 64%. Four factors were associated with lower survival: older age, use of Cy-TAI, any form of treatment prior to transplantation (either androgens or immunosuppressive therapy, [IST]), and grade II to IV acute graft-versus-host disease (GvHD). TAI was the sole factor associated with the occurrence of acute GvHD. The risk of cancers (15-year cumulative incidence, 10.9%) was associated with older age and with the use of cyclosporine as IST before transplantation. Cumulative incidences and risk factors of nonmalignant late effect including avascular osteonecrosis and late bacterial, viral, and fungal infection were also analyzed. Improved results using Cy-ATG as conditioning can lead to more than 90% chance of cure in patients with SAA. Even if, in our experience, the role of Cy-ATG versus that of Cy-TAI remained inextricably related to the year of transplantation, the major detrimental role of the GvHD disease in the long-term outcome and its relation to TAI supports avoidance of irradiation in the conditioning regimen. Furthermore, avoidance of any IST before transplantation in patients with a sibling donor is a prerequisite for attaining such excellent results.

Graft-versus-host disease following marrow transplantation for aplastic anemia: different impact of two GVHD prevention strategies

“…The incidence of acute and chronic GVHD in the control population appears high compared to that described in the literature. 4,5,23 This may be related to differences in the patient populations as the majority of previous studies included both pediatric and adult patients. Our study was confined only to adult patients.…”

“…In addition to CsA and MTX, some centers use antithymocyte globulin (ATG) in conditioning protocols for AA. 4,5 Despite these strategies, 30-40% of patients develop acute and chronic GVHD, which not only result in morbidity and mortality but also have a negative impact on the quality of life. [4][5][6][7] Unlike hematologic malignancies, GVHD probably has no therapeutic benefit in patients with AA and prevention of GVHD is one of the most desirable goals of BMT in AA.…”

“…4,5 Despite these strategies, 30-40% of patients develop acute and chronic GVHD, which not only result in morbidity and mortality but also have a negative impact on the quality of life. [4][5][6][7] Unlike hematologic malignancies, GVHD probably has no therapeutic benefit in patients with AA and prevention of GVHD is one of the most desirable goals of BMT in AA. Previous studies from St George's Hospital in London reported a favorable effect on acute and chronic GVHD in matched sibling donor and matched unrelated donor BMT for AA using in vivo anti-CD52 monoclonal antibodies (Campath-1G antibodies and alemtuzumab).…”

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

“…59,60,62 Among 133 patients with aplastic anemia undergoing allogeneic HCT, pre-HCT immunosuppressive therapy with cyclosporine (a group 1 carcinogen according to the International Agency for Research on Cancer) 124 was associated with five-fold higher rates of SN. 75 …”

Long-term outcome of childhood aplastic anemia patients who underwent allogeneic hematopoietic SCT from an HLA-matched sibling donor in Japan

“…3,4 In SAA, LM are also reported in the patients with HSCT and its occurrence is related to radiation-containing conditioning regimen and GVHD grade in adults, 5,6 however, the incidence and prognostic factors of LM in children with SAA who undergo HSCT are totally unknown.…”