Outcome of alternative donor transplantation for severe aplastic anemia can be comparable to outcome with matched related donors

Abstract

Matched related donor (MRD) bone marrow transplantation is the treatment of choice for pediatric patients with severe aplastic anemia (SAA); however, only 25% of patients will have an HLA-identical sibling. Alternative donor transplants may be an option for these patients, but such therapies have been associated with greater incidences of graft failures and graft-versus-host disease (GVHD). We retrospectively analyzed 32 pediatric patients who have undergone 34 hematopoietic stem cell transplants for severe aplastic anemia at our institution from April 1997 to April 2005. One patient had a MRD transplant followed by a matched unrelated donor (MUD) transplant, while another had an HLA-mismatched unrelated donor (MMUD) transplant followed by a transplant from a haplo-identical parent. Twelve patients received MRD transplants, whereas 18 patients received alternative donor transplants—11 MUD, 3 haplo-identical, and 4 MMUD. The median age at transplant was 9 years (range 1.5 to 18.4 yrs). For MRD transplants, the conditioning regimen most often utilized cyclophosphamide 50 mg/kg × 4 days and ATG 30 mg/kg × 3 days. For alternative donor transplants, the conditioning regimen most often utilized cyclophosphamide 50 mg/kg × 4 days, Campath 3-10 mg × 4 days (dependent upon patient weight) or ATG 30 mg/kg × 3 days, and TBI (single fraction 200 cGy for MUD; two fractions 200 cGy for MMUD). Nine alternative donor recipients received ATG in their preparative regimens, whereas 11 received Campath. GVHD prophylaxis was either FK506 or cyclosporine ± mini-methotrexate. The overall survival for MRD patients was 91.7% versus 80% for alternative donor patients at a median follow-up of 47 months (range 3 to 100 months). Of our 32 patients, there were 5 deaths: pulmonary failure with extensive, chronic GVHD (n = 1); poor graft function with infection (n = 1); and infection (n = 3). For patients receiving alternative donor transplants, the overall survival for the Campath group was 81.8% vs. 77.8% in the ATG group. None of the Campath patients developed extensive, chronic GVHD compared to 3/9 ATG patients. In conclusion, alternative donor transplantation using Campath or ATG in the preparatory regimens offers a curative therapy for pediatric SAA patients with survival similar to that of patients receiving matched sibling transplants. Although follow-up is shorter, Campath may be associated with a reduced incidence of extensive, chronic GVHD and further investigation is warranted.