Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome (WAS)
Condition: Wiskott-Aldrich Syndrome
MeSH terms: Wiskott-Aldrich Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Wiskott-Aldrich syndrome (WAS) is a rare X-linked congenital immune-deficiency syndrome and
      hematopoietic stem cell transplantation (HSCT) has become a curative modality. But the
      transplant with the conventional conditioning resulted in high incidence of treatment related
      toxicities and non-myeloablative conditioning resulted in high incidence of engraftment
      failure. Recently, fludarabine based reduced toxicity myeloablative conditioning regimen was
      developed for adult myeloid malignancies with promising result of good engraftment and low
      treatment related toxicities. To increase the engraftment potential without serious
      complication, reduced toxicity myeloablative conditioning regimen composed of fludarabine,
      busulfan, and thymoglobulin is designed for Wiskott-Aldrich syndrome.
    

Detailed description: 
      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 WAS.
    

Intervention name(s): Fludarabine, Busulfan, Thymoglobulin
Intervention type(s): Drug
Intervention description(s): fludarabine (40 mg/m2 once daily i.v. on days -8, -7, -6, -5, -4 & -3) busulfan (0.8 mg/kg every 6 hours i.v. on days -6, -5, -4, & -3) thymoglobulin (2.5 mg/kg once daily i.v. on days -8, -7, -6 for cord blood and on days -4, -3, -2 for bone marrow or mobilized peripheral blood)
Intervention MeSH terms: Fludarabine; Busulfan; Thymoglobulin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Wiskott-Aldrich syndrome; HSCT