title: Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for Dedicator-of-Cytokinesis 8 Deficiency Using Post-Transplantation Cyclophosphamide.
abstract: Dedicator-of-cytokinesis 8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplantation (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/Cy) for graft-versus-host disease (GVHD) prophylaxis. Seven patients with DOCK8 deficiency (median age, 20 years; range, 7 to 25 years) received a haploidentical related donor HSCT. The conditioning regimen included 2 days of low-dose cyclophosphamide, 5 days of fludarabine, 3 days of busulfan, and 200 cGy total body irradiation. GVHD prophylaxis consisted of PT/Cy 50 mg/kg/day on days +3 and +4 and tacrolimus and mycophenolate mofetil starting at day +5. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively. All patients attained >90% donor engraftment by day +30. Four subjects developed acute GVHD (1 with maximum grade 3). No patient developed chronic GVHD. With a median follow-up time of 20.6 months (range, 9.5 to 31.7 months), 6 of 7 patients are alive and disease free. Haploidentical related donor HSCT with PT/Cy represents an effective therapeutic approach for patients with DOCK8 deficiency who lack a matched related or unrelated donor.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: Nirali.Shah@nih.gov.
authors.forename: Nirali N
authors.initials: NN
authors.lastname: Shah
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.affiliation: Laboratory of Host Defense, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Helen
authors.initials: H
authors.lastname: Su
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kristen
authors.initials: K
authors.lastname: Cole
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Parta
authors.affiliation: Oral Immunity and Inflammation Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland.
authors.forename: Niki M
authors.initials: NM
authors.lastname: Moutsopoulos
authors.affiliation: Division of Pediatric Allergy and Immunology, Ministry of Health, Marmara University, Training and Research Hospital, Istanbul, Turkey.
authors.forename: Safa
authors.initials: S
authors.lastname: Baris
authors.affiliation: Division of Pediatric Allergy and Immunology, Ministry of Health, Marmara University, Training and Research Hospital, Istanbul, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Karakoc-Aydiner
authors.affiliation: Clinical Center Pharmacy Department, National Institutes of Health, Bethesda, Maryland.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hughes
authors.affiliation: Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Heidi H
authors.initials: HH
authors.lastname: Kong
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Steve M
authors.initials: SM
authors.lastname: Holland
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
mesh_terms: D003520:Cyclophosphamide / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods; D000075442:Transplantation, Haploidentical / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D003520:Cyclophosphamide
keywords: Dedicator-of-cytokinesis-8 (DOCK8) deficiency; Haploidentical transplantation; Immune reconstitution