J Korean Med Sci 2008; 23: 146-8 ISSN 1011-8934 DOI: 10.3346/jkms.2008.23.1.146 Copyright The Korean Academy of Medical Sciences Unrelated Bone Marrow Transplantation with a Reduced Toxicity Myeloablative Conditioning Regimen in Wiskott-Aldrich Syndrome Wiskott-Aldrich syndrome (WAS) is an X-linked congenital immune-deficiency syn- drome, and bone marrow transplantation (BMT) has become a curative modality. However, the transplant with the alternative donor needed more intensive condi- tioning with increased treatment-related toxicities. Recently, fludarabine-based reduc- ed toxicity myeloablative conditioning regimens have been developed for adult myeloid malignancies with promising results of good engraftment and low treatment-relat- ed toxicities. To increase the engraftment potential without serious complications, a boy with WAS received successful unrelated BMT with a reduced toxicity myeloab- lative conditioning regimen composed of fludarabine (40 mg/m2 on days -8, -7, -6, -5, -4, -3), busulfan (0.8 mg/kg i. v. q 6 hr on days -6, -5, -4, -3), and thymoglobulin (2.5 mg/kg on days -4, -3, -2). This novel conditioning regimen could improve the outcome of allogeneic transplantation for other non-malignant diseases such as congenital immune-deficiency syndromes or metabolic storage diseases. Key Words : Wiskott-Aldrich Syndrome; Bone Marrow Transplantation; Busulfan; Fludarabine Hyoung Jin Kang, Hee Young Shin, Sun Hie Ko, Jeong Ah Park, Eun Kyung Kim, Jung Woo Rhim, Joong Gon Kim, Hyo Seop Ahn Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea Received : 8 January 2007 Accepted : 21 February 2007 Address for correspondence Hyo Seop Ahn, M.D. Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea Tel : +82.2-2072-3625, Fax : +82.2-743-3455 E-mail : hsahn@snu.ac.kr *This study was supported by grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A050089). INTRODUCTION Wiskott-Aldrich syndrome (WAS) is an X-linked congen- ital immune-deficiency syndrome characterized by the triad of recurrent infection, eczema, and thrombocytopenia, and bone marrow transplantation (BMT) from an HLA-matched related donor is an effective treatment (1, 2). Patients with- out an appropriate related donor could receive an alternative stem cell source such as matched unrelated donor or cord blood. However, the transplant with the alternative donor needed more intensive conditioning to overcome the hema- tologic and immunologic barrier with increased treatment- related toxicity. Recently, fludarabine-based reduced toxici- ty myeloablative conditioning regimens have been develop- ed for adult myeloid malignancies with promising results of good engraftment and low treatment related toxicities (3-5). To increase the engraftment potential without serious com- plications, a boy with WAS received BMT from a matched unrelated donor with a reduced toxicity myeloablative con- ditioning regimen. CASE REPORT A 3-yr-old boy was admitted because of eczema, recurrent 146 infection, and thrombocytopenia with a platelet count less than 10×109/L and was diagnosed as having WAS with a large deletion in the exon 1 to 11 of the WAS gene (Fig. 1). For the detection of mutation, the following primers were used; exon 1 forward 5′-GGT TTT TTG CAT TTC CTG TTC- 3′and exon 1 reverse 5′-AGG AAG AGG AAG AAA CGG TG-3′, exon 2 forward 5′-CCT GAC CAG ACT CCA CTG AC-3′and exon 2 reverse 5′-CTT GAA GCT ATG GAC ACA TAT G-3′, exon 3 forward 5′CCT CAG TGC CAC TGT GCC TC3′and exon 3 reverse 5′-TTC CCA TCT CCT CTC CAC AC-3′, exon 4 forward 5′-GTG TGG AGA GGA GAT GGG AA-3′and exon 4 reverse 5′-CAC TCA CCT CTG CCC AAC TT-3′, exon 5 forward 5′-AAG TTG GGC AGA GGT GAG TG-3′and exon 5 reverse 5′-AGA GAG TTA TCA CAG CCC TG-3′, exon 6 forward 5′-GGC TGT GAT AAC TCT CTA CA-3′and exon 6 reverse 5′-CCA TCC ATC CAG AGA CAC AG-3′, exon 7 forward 5′-TGG TAA GTG GGT CAA TGA GC-3′and exon 7 reverse 5′- CAG CTG TCC ACT TGT TCA TG-3′, exon 8 forward 5′-AAG GAA GGG CAG TGA GGA TT-3′and exon 8 reverse 5′-GGT GGA AGT TTA GTG GAG TC-3′, exon 9 forward 5′-CGC CTT ATT CCT CTA CTC CT-3′and exon 9 reverse 5′-GAC TGA GTG ACT TAG TGC GT-3′, exon 10-1 forward 5′-TCA GTC AGG AGT TGG TCA GT-3′and exon 10-1 reverse 5′-GTC CAG AAC GTC CAG