Phase I/II Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome
Wiskott-Aldrich syndrome (WAS) is an rare X-linked congenital immune-deficiency syndrome
characterized by the triad of recurrent infection, eczema and thrombocytopenia with small
size of platelet (Puck JM, 2006). Clinical studies revealed high rate of autoimmune disorder
and malignancy in WAS (Ochs HD, 2006). The identification of the molecular defect in 1994
(Derry JM, 1994) has broadened the clinical spectrum of the syndrome to include chronic or
intermittent X-linked thrombocytopenia (XLT), a relatively mild form of WAS and X-lined
neutropenia caused by an arrest of myelopoiesis (Ochs HD, 2006).
The incidence of WAS in Korea was very low and only 6 patients diagnosed between 2001 and
2005 (Kim JG, 2006).
Conventional treatments for WAS such as prophylactic antibiotics and immune globin for
infection and platelet transfusion for bleeding were not so successful (Thrasher AJ, 2000).
Bone marrow transplantation (BMT) from an HLA-matched related donor is an effective
treatment (Filipovich AH, 2001) and patients without appropriate related donor could receive
alternative stem cell source such as matched unrelated donor or cord blood. But the
transplant with the alternative donor needed more intensive conditioning to overcome the
hematologic and immunologic barrier with increased treatment related toxicity. Further
progress depends in particular on the development of alternative preparative conditioning
regimens which allow stable engraftment of donor precursor cells with minimal systemic toxic
side effects (Friedrich W, 2004).
Recently, we reported successful unrelated bone marrow transplantation in a boy with WAS
with reduced toxicity myeloablative conditioning regimen to increase the engraftment
potential without serious complication (Kang, 2008), and extended to multicenter phase I/II
pilot study with this reduced toxicity myeloablative conditioning regimen in the HSCT for
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for HSCT in WAS.
Feb. 2007 to Jan. 2012
Hyo Seop Ahn, Ph. D
The Korean Society of Pediatric Hematology Oncology
Korea: Food and Drug Administration