title: Matched related and unrelated donor hematopoietic stem cell transplantation for DOCK8 deficiency.
abstract: We performed allogeneic hematopoietic stem cell transplantation in 6 patients with mutations in the dedicator-of-cytokinesis-8 (DOCK8) gene using a myeloablative conditioning regimen consisting of busulfan 3.2 mg/kg/day i.v. for 4 days and fludarabine 40 mg/m(2)/day for 4 days. Three patients received allografts from matched related donors and 3 patients from matched unrelated donors. Two patients received peripheral blood stem cells and 4 patients bone marrow hematopoietic stem cells. Tacrolimus and short-course methotrexate on days 1, 3, 6, and 11 were used for graft-versus-host-disease (GVHD) prophylaxis. All 6 patients are alive at a median follow-up of 22.5 months (range, 14 to 35). All patients achieved rapid and high levels of donor engraftment and complete reversal of the clinical and immunologic phenotype. Adverse events consisted of acute skin GVHD in 2 patients and post-transplant pulmonary infiltrates in a patient with extensive bronchiectasis pretransplant. Thus, a uniform myeloablative conditioning regimen followed by allogeneic hematopoietic stem cell transplantation in DOCK8 deficiency results in reconstitution of immunologic function and reversal of the clinical phenotype with a low incidence of regimen-related toxicity.
authors: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Jennifer
authors: J
authors: Cuellar-Rodriguez
authors: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Alexandra F
authors: AF
authors: Freeman
authors: Division of Hematology and Hematologic Malignancies, Alberta Health Services, Calgary, Alberta, Canada.
authors: Jennifer
authors: J
authors: Grossman
authors: Laboratory of Host Defense, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Helen
authors: H
authors: Su
authors: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc. (formerly SAIC-Frederick, Inc.), Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors: Mark
authors: M
authors: Parta
authors: Laboratory of Host Defense, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Heardley
authors: H
authors: Murdock
authors: Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors: Nirali
authors: N
authors: Shah
authors: Center for Cancer and Immunology Research at the Children's Research Institute, Children's National Medical Center, Washington, DC.
authors: Catherine
authors: C
authors: Bollard
authors: Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors: Heidi H
authors: HH
authors: Kong
authors: National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland.
authors: Niki
authors: N
authors: Moutsopoulos
authors: Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Kelly
authors: K
authors: Stone
authors: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors: Juan
authors: J
authors: Gea-Banacloche
authors: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Steven M
authors: SM
authors: Holland
authors: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: hicksted@mail.nih.gov.
authors: Dennis D
authors: DD
authors: Hickstein
mesh_terms: D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000627:therapeutic use; D002648:Child; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D009154:Mutation; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D010865:Pilot Projects; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D035781:Siblings; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D016559:Tacrolimus; D008727:Methotrexate
keywords: Allogeneic; DOCK8 deficiency; Transplantation
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