Allogeneic stem cell transplantation (SCT) is curative for Wiskott Aldrich syndrome (WAS), an X-linked disorder with thrombocytopenia, immune deficiency, and susceptibility to malignancy/autoimmunity. Standard myeloablative conditioning regimen for SCT often result in lasting toxicities. Hence, we used reduced intensity conditioning (RIT) in 2 patients whose disease manifestations included infections and hemorrhage. Methods: The 2 males (R1 and R2), 7 and 8 months old, underwent SCT with bone

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... rrow from a HLA identical sibling and 10/10 allele matched unrelated donor respectively. Conditioning consisted of 23 and 28 mg of Campath-1H (targeted dose was 33 mg) on days -22 and -19, fludarabine (1.0 mg/kg/ day) on day -8 to -4, and melphalan (4.7 mg/kg) on day -3. GVHD prophylaxis included cyclosporine, short course methotrexate, and methylprednisolone. GCSF was administered until neutrophil engraftment. Results: Campath-1H was associated with vasculitic edema and blisters in R1 resulting in lowered dosing. R2 received a lower dose following an unrelated aspiration episode. Neutrophils engrafted (ANC Ն500/dl) on days 15 and 12; platelets engrafted (Ն20,000/dl) on days 70 and 13 respectively. Neither developed Նgrade 2 GVHD or severe organ toxicity. R1 is off immunosuppression and R2 is on a cyclosporine taper. By molecular analysis 9 months post SCT, R1 has 81% lymphoid and 22% myeloid; R2 has 100% lymphoid and 65% myeloid donor chimerism that is stable post immunosuppression taper. R2 developed autoimmune hemolytic anemia that responded to rituximab therapy. Neither had bleeding complications. Lymphocyte subpopulations and function were recovering 6 months post SCT. Conclusions: This reduced intensity conditioning achieved mixed donor chimerism in 2 patients with WAS, resulting in transfusion independence and amelioration of bleeding complications. SCT was not associated with significant organ toxicity or GVHD. Monitoring for durability of engraftment and other transplant related complications is in progress. A reduced intensity transplant that allows stable donor engraftment and limits chemotherapy may spare young patients toxicities of standard conditioning and merits further investigation.