Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age

Abstract

Patients with severe aplastic anemia (SAA) over 40 years of age are often not offered treatment with hematopoietic cell transplantation (HCT) because of concerns about treatment-related morbidity or mortality. To evaluate this risk, we analyzed outcomes after allogeneic HCT from HLA-identical sibling donors for all older patients with SAA at our center since 1988. The 23 consecutive patients ranged in age from 40 to 68 years. The conditioning regimen was cyclophosphamide (200 mg/kg) and horse antithymocyte globulin. Methotrexate and cyclosporine were given for postgrafting immunosuppression. The cumulative incidences of grades II, III, and IV acute graft-versus-host-disease were 30%, 4%, and 0%, respectively; that for chronic GVHD was 26%. With a median follow-up of 9.1 years, overall survival was 65%. Documented infections within 1 month before HCT were significantly associated with risk of early treatment-related mortality (P < .001). The median time to discontinuation of posttransplant immunosuppression was 6.2 (range: 5.9-92.0) months. Three patients developed superficial basal cell carcinoma between 5.5 and 15 years after HCT. Our data favor a practice of extending HLA-identical sibling HCT for treatment of SAA in patients older than 40 years of age who are without significant medical comorbidities.

Figure 1

(A) Cumulative incidence and onset of acute graft versus host disease (GVHD, 30.4% grade II, 4.3% grade III). (B) Cumulative incidence and onset of chronic graft versus host disease (26%). (C) Upper curve shows declining proportion of patients continuing post-grafting immunosuppression therapy (IST), lower curve shows cumulative incidence of death or rejection while on immunosuppression therapy. Area between curves represents proportion of patients who are alive, rejection free and on immunosuppression therapy. (D) Overall survival after HLA-identical hematopoietic cell transplantation (HCT) for severe aplastic anemia (SAA) for all patients (n=23) over 40 years of age (65% survival at 10 years). Tick marks indicate time of last follow-up.