Alexander Ngwube
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Lisa Forbes, MD
,
Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Robert A. Krance, MD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, TX
Malcolm Brenner, MD, PhD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, TX
Helen E. Heslop, MD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX
Kathryn Leung, MD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Imelda C Hanson, MD
,
Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Ghadir Sasa, MD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Howard Rosenblatt, MD
,
Department of Allergy/Immunology, Baylor College of Medicine, Houston, TX
Ann M. Leen, PhD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, TX
William Shearer, MD, PhD
,
Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Swati Naik, MD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Nabil M Ahmed, MD, MPH
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Stephen Gottschalk, MD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, TX
Carl Allen, MD, PhD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Caridad Martinez, MD
,
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Background:Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a triad of immunodeficiency, eczema and thrombocytopenia. This is as a result of mutation in the WASP gene that regulates actin polymerization in hematopoietic cells. Currently, stem cell transplant (SCT) is the most reliable curative treatment with excellent results for patients with HLA-matched family or unrelated donors. However, mixed donor chimerism even in the setting of full myeloablative regimens is still a significant problem since mixed chimerism affecting the myeloid compartment may result in persistent thrombocytopenia. Thus, identifying factors associated with mixed donor chimerism after SCT in WAS patients is extremely important.
Methods:We performed a retrospective chart review of eleven children who underwent allogeneic transplant for WAS to identify any factors (i.e. pretransplant health of the patients, degree of thrombocytopenia, conditioning regimen, infection, peri-transplant factors, TH2 flare) that may be associated with mixed donor chimerism.
Results:The median age at transplant was 16 months (range 3-39) and the donor was MRD in 4, MUD in 5 and MMUD in 2. All patients received bone marrow apart from one who received cord. The mean WAS score was 2.7 (range 1-5) and diagnosis was confirmed by genetic testing in all patients. All were conditioned with myeloablative regimens. Nine received buslfan, cyclophosphamide, Ara-C or fludarabine and campath while 2 patients got busulfan, cyclophosphamide and ATG.The median nucleated cell dose from the marrow was 5.3 x 109/kg (range 3 to 7.9). The median times to neutrophil and platelet engraftment were 22.5 (range 13-27) and 19 (range 17-31) days respectively. The overall survival by Kaplan Meier anlalysis is 91%, 95%CI: 51%-99% at 2 year post transplant. Only one patient developed grade IV aGvHD and died on Day +99. Five of eleven (45%) had mixed donor chimerism, (range: 7-50%). Of these 5 patients, 2 had normalization of the platelet count despite the mixed chimerism, 2 had full donor chimerism after receiving a second transplant with the same donor, and 1 remains transfusion dependent awaiting a 2nd transplant. No statistically significant difference was found between WAS scores, donor type, conditioning, stem cell source, age at transplant and mixed chimerism amongst the eleven patients.
Conclusions: Although the overall survival of our patient population was excellent, it does not reflect a uniform result in terms of engraftment. None of our peri-transplant parameters are predictive of mixed chimerism or engraftment outcome. More correlative work is needed to assess genotype-phenotype risk factors for engraftment as well as pre transplant immunologic and disease states to better assess the risk of mixed chimerism and guide interventions to promote engraftment.
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