Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party

Abstract

Summary:We have developed a reduced-intensity conditioning regimen for patients with severe aplastic anemia (SAA) undergoing alternative donor transplants, which includes fludarabine (120 mg/m 2 ), cyclophosphamide (1200 mg/m 2 ) and antithymocyte globulin (7.5 mg/kg). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate. We have enrolled 38 SAA patients in this trial: median age of 14 (3-37) years, transplanted from unrelated (n ¼ 33) or family mismatched (n ¼ 5) donors, with unmanipulated marrow (n ¼ 36) or peripheral blood (n ¼ 2). Seven patients (18%) had evidence of graft failure, 11% developed grade II-III acute GvHD and 27% developed chronic GvHD. The actuarial 2-year survival is 73%, with a median follow-up of 621 days. Younger patients (p14 years) had a lower risk of rejection (5%) and improved actuarial survival (84%). Causes of death were infections (n ¼ 3), graft failure (n ¼ 2), Epstein-Barr virus lymphoma (n ¼ 2) and hemorrhage (n ¼ 2). In conclusion, the actuarial 2-year survival is encouraging in young SAA patients receiving a radiation-free conditioning regimen. The significant risk of graft failure in patients 15 years or older may require modification of the conditioning regimen in adults. Bone Marrow Transplantation (2005) 36, 947-950.

A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia

“…1 Various attempts have been made over the years to improve OS by reducing graft failure and GVHD, but there are few related reports and most data come from very small patients number. [16][17][18][19] Chan and EBMT report successful mismatched HSCT with a fludarabine-based conditioning regimen (plus CY and ATG) for SAA patients, their data are from only 3-5 cases with only one Ag-mismatched case. 16,17 Various doses of irradiation were added to the conditioning regimen to achieve sustained engraftment.…”

Treatment strategies for patients with severe aplastic anemia

“…17 In young patients under the age of 15 years, the outcome is excellent with 84% 2-year survival and 5% rejection. In older patients the results are less favourable with 61% survival and 32% rejection.…”

Decision-Making and Problem Solving

“…A median of 32 patients (range 11-349, total 1,645) were investigated in the total study population of 14 studies 11,[15][16][17][21][22][23][25][26][27][28][29]31,32 and in 8 relevant subgroups of 4 other studies. 10,20,24,30 The patients' median age in the individual studies was between eight and 27 years and the ratio of males : females ranged from a male (30 : 10) to a female preponderance (11 : 20).…”

“…The study design was reported as prospective in one controlled trial 26 and in 4 case series. 15,16,20,24 A consecutive enrolment was stated in 3 23,25,27 of 13 retrospective case series. 10,11,17,[21][22][23]25,[27][28][29][30][31][32] Transplantations were performed between 1981 and 2006.…”

“…10,15,23,26 DNA-based HLA-typing was performed for all participants in 5 published studies, 16,20,28,29,31 and for the majority of participants in 5 other studies. 15 10,17,20,21,23,25,[27][28][29][30][31][32] Reactivation of disease caused by cytomegalovirus and Epstein-Barr virus was observed in 3 studies. 23,31,32 In the controlled trial, 205 children and young people under 18 years of age with SAA were enrolled, 26 of whom 198 were treated with IST.…”