title: Nonmyeloablative allogeneic hematopoietic stem cell transplantation for GATA2 deficiency.
abstract: We treated 14 patients with GATA2 deficiency using a nonmyeloablative allogeneic hematopoietic stem cell transplantation regimen. Four patients received peripheral blood stem cells from matched related donors (MRD), 4 patients received peripheral blood stem cells from matched unrelated donors (URD), 4 patients received hematopoietic stem cells from umbilical cord blood donors (UCB), and 2 patients received bone marrow cells from haploidentical related donors. MRD and URD recipients received conditioning with 3 days of fludarabine and 200 cGy total body irradiation (TBI). Haploidentical related donor recipients and UCB recipients received cyclophosphamide and 2 additional days of fludarabine along with 200 cGY TBI. MRD, URD, and UCB recipients received tacrolimus and sirolimus for post-transplantation immunosuppression, whereas haploidentical recipients received high-dose cyclophosphamide followed by tacrolimus and mycophenolate mofetil. Eight patients are alive with reconstitution of the severely deficient monocyte, B cell, and natural killer cell populations and reversal of the clinical phenotype at a median follow-up of 3.5 years. Two patients (1 URD recipient and 1 UCB recipient) rejected the donor graft and 1 MRD recipient relapsed with myelodysplastic syndrome after transplantation. We are currently using a high-dose conditioning regimen with busulfan and fludarabine in patients with GATA2 deficiency to achieve more consistent engraftment and eradication of the malignant myeloid clones.
authors.affiliation: Division of Hematology and Hematologic Malignancies, Alberta Health Services, Calgary, Alberta, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Grossman
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cuellar-Rodriguez
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Juan
authors.initials: J
authors.lastname: Gea-Banacloche
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Christa
authors.initials: C
authors.lastname: Zerbe
authors.affiliation: Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: Katherine
authors.initials: K
authors.lastname: Calvo
authors.affiliation: Department of Pharmacy, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hughes
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Fran
authors.initials: F
authors.lastname: Hakim
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Kristen
authors.initials: K
authors.lastname: Cole
authors.affiliation: Leidos Biomedical Research, Inc, Frederick, Maryland; Intramural Clinical Management & Operations Branch, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Parta
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Freeman
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland. Electronic address: hicksted@mail.nih.gov.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D002648:Child; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D005500:Follow-Up Studies; D050989:GATA2 Transcription Factor / Q000172:deficiency*; D030342:Genetic Diseases, Inborn / Q000097:blood / Q000235:genetics / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000628:therapy*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage; D019172:Transplantation Conditioning; D061349:Unrelated Donors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation
chemical_list: D000970:Antineoplastic Agents; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D007166:Immunosuppressive Agents; D014740:Vidarabine; C024352:fludarabine; D020123:Sirolimus; D016559:Tacrolimus
keywords: Familial acute myelogenous leukemia; GATA2; Hematopoietic stem cell transplantation; Myelodysplastic syndrome
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