1. ¹Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescence Medicine, Medical University of Graz, Graz, Austria
2. ²Department of Pediatric Hematology/Oncology, Medical School Hannover, Germany

Correspondence: Dr M Benesch, Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescence Medicine, Medical University of Graz, Auenbruggerplatz 30, A-8036 Graz, Austria. E-mail: martin.benesch@klinikum-graz.at

Received 26 August 2004; Accepted 27 October 2004; Published online 24 January 2005.

Abstract

Conditioning including total body/lymphoid irradiation is widely used to prevent graft rejection in patients with refractory severe aplastic anemia (SAA) undergoing hemopoietic cell transplantation (HCT) from alternative donors and or after graft manipulation. To reduce regimen-related toxicity we transplanted three children with refractory SAA after conditioning with radiotherapy-free regimens. Conditioning included fludarabine 175–180 mg/m² in all patients. In addition, patient 1 (failing two previous grafts) received thiotepa 10 mg/kg and Campath-1H 60 mg/m²; patient 2 cyclophosphamide 120 mg/kg, thiotepa 15 mg/kg and OKT-3 0.1 mg/kg/day for 4 weeks; and patient 3 cyclophosphamide 120 and ATG 90 mg/kg. Stem cell source was unmanipulated marrow from the same unrelated donor as for the two previous transplantations in patient 1 and CD34⁺-purified peripheral blood stem cells from an HLA-matched unrelated donor and from the haploidentical mother in patients 2 and 3. Only patient 1 received graft-versus-host disease (GVHD) prophylaxis with cyclosporine A and mycophenolate mofetil. Follow-up is now 30, 51, and 15 months. None of the patients developed GVHD. All patients have normal counts with complete donor chimerism. Fludarabine-based conditioning is powerfully immunosuppressive and may be used for children with refractory SAA undergoing HCT from alternative donors even after rejection following previous HCT.