Allogeneic Hematopoietic Stem Cell Transplantation Of Patients With Wiskott-Aldrich Syndrome With Total Body Irradiation (TBI), Thiotepa and Fludarabine Or Cyclophosphamide Followed By T-Cell Depleted Grafts From Alternative Donors

Wiskott-Aldrich syndrome (WAS) is a rare X-linked congenital immunodeficiency syndrome characterized by micro-thrombocytopenia, eczema, autoimmune syndromes and malignancies that are often fatal. Early hematopoietic stem cell transplant (HSCT) experience for patients with WAS from alternative donors was associated with poor outcome including a high rate of graft rejection. Since 1998 we have transplanted 13 patients with WAS with grafts from alternative donors. Specifically, 9 of these patients received T cell depleted transplants and are the focus of this abstract. Grafts were from matched unrelated donors (N=5) mismatched unrelated donors (N=2) mismatched related donors (N=2). Patient age at transplant ranged from 1.1-21.5 years (median 3.3). Cytoreduction included Hyperfractionated TBI with Thiotepa and Cyclophosphamide or Fludarabine (N=7) Busulfan with Melphalan and Fludarabine (N=1) Cyclophosphamide with Thiotepa and Fludarabine (N=1). Prior to 2002 no children under 24 months received TBI. Subsequently CNS shielding was used with TBI for patients under the age of 3. All patients received ATG for graft rejection prophylaxis. Six patients had previously undergone splenectomy. Stem cell grafts were Lectin/E rosette separated T cell depleted bone marrow (N=4) or Isolex/E rosette separated T-cell depleted PBSC (N=5). Eight patients engrafted with median neutrophil engraftment on day 12 (11 -16). One patient who received cytoreduction with Cyclophosphamide, Thiotepa and Fludarabine suffered primary graft failure, had autologous recovery and went on to receive a second transplant and is alive and well. All patients developed Grade I – II mucositis. One patient suffered an early toxic death after developing acute encephalopathy during cytoreduction with Busulfan (8mg/kg) Melphalan (140mg/m2) and Fludarabine (125mg/m2) and one other patient with a prior history of lymphoma had progression of lymphoma and early death post HSCT. One developed acute GvHD (Grade III GI). Three patients developed autoimmune disorders associated with mixed chimerism. All three patients had complete resolution of their autoimmune disease and two of these three patients reverted to full donor chimerism. With a post HSCT follow-up period of a median of 7.5 years (3-15 years) seven of these nine patients are alive and disease-free. In summary, T-cell depleted grafts appear to extend transplant as a treatment option for patients with WAS who are without matched related donors. Recent successful experience with T cell depletion following chemotherapy only regimens for other patient populations will provide a way to explore non-TBI based cytoreduction and T cell depletion as an approach for future patients.