title: Successful allogeneic hematopoietic stem cell transplantation for GATA2 deficiency.
abstract: We performed nonmyeloablative HSCT in 6 patients with a newly described genetic immunodeficiency syndrome caused by mutations in GATA2-a disease characterized by nontuberculous mycobacterial infection, monocytopenia, B- and NK-cell deficiency, and the propensity to transform to myelodysplastic syndrome/acute myelogenous leukemia. Two patients received peripheral blood stem cells (PBSCs) from matched-related donors, 2 received PBSCs from matched-unrelated donors, and 2 received stem cells from umbilical cord blood (UCB) donors. Recipients of matched-related and -unrelated donors received fludarabine and 200 cGy of total body irradiation (TBI); UCB recipients received cyclophosphamide in addition to fludarabine and TBI as conditioning. All patients received tacrolimus and sirolimus posttransplantation. Five patients were alive at a median follow-up of 17.4 months (range, 10-25). All patients achieved high levels of donor engraftment in the hematopoietic compartments that were deficient pretransplantation. Adverse events consisted of delayed engraftment in the recipient of a single UCB, GVHD in 4 patients, and immune-mediated pancytopenia and nephrotic syndrome in the recipient of a double UCB transplantation. Nonmyeloablative HSCT in GATA2 deficiency results in reconstitution of the severely deficient monocyte, B-cell, and NK-cell populations and reversal of the clinical phenotype. Registered at www.clinicaltrials.gov as NCT00923364.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Cancer Institute (NCI), USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cuellar-Rodriguez
authors.forename: Juan
authors.initials: J
authors.lastname: Gea-Banacloche
authors.forename: Alexandra F
authors.initials: AF
authors.lastname: Freeman
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.forename: Christa S
authors.initials: CS
authors.lastname: Zerbe
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Calvo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wilder
authors.forename: Roger
authors.initials: R
authors.lastname: Kurlander
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Olivier
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D050989:GATA2 Transcription Factor / Q000172:deficiency / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000235:genetics / Q000628:therapy*; D010865:Pilot Projects; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human