title: Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency.
abstract: Dedicator of cytokinesis 8 (DOCK8) deficiency can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Reports of outcomes are still limited.
  
  
  
  We sought to analyze the results of HSCT in patients with DOCK8 deficiency and report whether approaches resulting in mixed chimerism result in clinically relevant immune reconstitution.
  
  
  
  We performed a retrospective chart review of 11 patients with DOCK8 deficiency and measured DOCK8 expression and cytokine production.
  
  
  
  Of 11 patients, 7 received HSCT from related and 4 from unrelated donors; 9 patients received busulfan-based conditioning regimens. Survival was excellent (10 [91%] of 11 patients alive), including a patient who had undergone liver transplantation. Patients showed significant improvements in the frequency and severity of infections. Although eczema resolved in all, food allergies and high IgE levels persisted in some patients. Lymphopenia, eosinophilia, low numbers of naive CD8(+) T cells and switched memory B cells, and TH1/TH2 cytokine imbalance improved in most patients. Although the 8 matched related or unrelated donor recipients had full donor chimerism, all 3 recipients of mismatched unrelated donor HSCT had high levels of donor T-cell chimerism and low B-cell and myeloid cell chimerism (0% to 46%). Almost all switched memory B cells were of donor origin. All patients, including those with mixed chimerism, mounted robust antibody responses to vaccination.
  
  
  
  Allogeneic HSCT ameliorated the infectious and atopic symptoms of patients with DOCK8 deficiency. In patients with mixed chimerism, selective advantage for donor-derived T cells and switched memory B cells promoted restoration of cellular and humoral immunity and protection against opportunistic infection.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait; Department of Pediatrics, Al-Sabah Hospital, Kuwait City, Kuwait.
authors.forename: Waleed
authors.initials: W
authors.lastname: Al-Herz
authors.affiliation: Division of Hematology-Oncology, Boston Children's Hospital, Boston, Mass; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass.
authors.forename: Julia I
authors.initials: JI
authors.lastname: Chu
authors.affiliation: Division of Hematology-Oncology, Boston Children's Hospital, Boston, Mass.
authors.forename: Jet
authors.initials: J
authors.lastname: van der Spek
authors.affiliation: Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
authors.forename: Raj
authors.initials: R
authors.lastname: Raghupathy
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Massaad
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Sevgi
authors.initials: S
authors.lastname: Keles
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Biggs
authors.affiliation: Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Cockerton
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Janet
authors.initials: J
authors.lastname: Chou
authors.affiliation: Division of Pediatric Infectious Diseases, American University of Beirut, Beirut, Lebanon.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Dbaibo
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Mass.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Elisofon
authors.affiliation: Division of Pediatric Infectious Diseases, American University of Beirut, Beirut, Lebanon.
authors.forename: Rima
authors.initials: R
authors.lastname: Hanna-Wakim
authors.affiliation: Department of Surgery, Boston Children's Hospital, Boston, Mass.
authors.forename: Heung Bae
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Boston Children's Hospital, Boston, Mass; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass.
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Lehmann
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: McDonald
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.affiliation: Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Talal A
authors.initials: TA
authors.lastname: Chatila
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
authors.affiliation: Great Ormond Street Hospital for Children, NHS Foundation Trust, London, United Kingdom; UCL Institute of Child Health, London, United Kingdom.
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.affiliation: Division of Hematology-Oncology, Boston Children's Hospital, Boston, Mass; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass. Electronic address: sung-yun.pai@childrens.harvard.edu.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Pai
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors
keywords: Primary immunodeficiency; conditioning; dedicator of cytokinesis 8 deficiency; hematopoietic stem cell transplantation; mixed chimerism