Allogeneic hematopoietic cell transplantation in patients with GATA2 deficiency-a case report and comprehensive review of the literature

Ann Hematol. 2018 Oct;97(10):1961-1973. doi: 10.1007/s00277-018-3388-4. Epub 2018 Jun 13.

Abstract

Recently, an immunodeficiency syndrome caused by guanine-adenine-thymine-adenine 2 (GATA2) deficiency has been described. The syndrome is characterized by (i) typical onset in early adulthood, (ii) profound peripheral blood cytopenias of monocytes, B lymphocytes, and NK cells, (iii) distinct susceptibility to disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections (particularly human papillomavirus), and (iv) a high risk of developing hematologic malignancies (myelodysplastic syndromes (MDS); acute myeloid leukemias (AML)). Considerable clinical heterogeneity exists among patients with GATA2 deficiency, but once infectious symptoms occur or MDS/AML arises, survival declines significantly. Allogeneic hematopoietic cell transplantation (HCT) currently provides the only curative treatment option for both MDS/AML and dysfunctional immunity with life-threatening opportunistic infections. Strategies regarding timing of allogeneic HCT, antimicrobial prophylaxis and treatment, intensity of the preparative regimen, and optimal donor and graft source have not been clearly defined due to the rarity of the disease. Here, we provide a comprehensive analysis of the available literature and published case reports on the use of allogeneic HCT in patients with GATA2 deficiency. In addition, a case of a young woman with GATA2 deficiency, who developed an immune reconstitution inflammatory syndrome in her mycobacterial skin lesions post allogeneic HCT is presented and illustrates distinct problems encountered in this disease context.

Keywords: Allogeneic hematopoietic cell transplantation; GATA2 deficiency; Immune reconstitution inflammatory syndrome; Myelodysplastic syndrome.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Child
  • Child, Preschool
  • Disease Susceptibility
  • Female
  • GATA2 Transcription Factor / deficiency*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / etiology*
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / therapy*
  • Male
  • Middle Aged
  • Mycobacterium Infections, Nontuberculous / etiology*
  • Mycobacterium Infections, Nontuberculous / immunology
  • Mycobacterium Infections, Nontuberculous / pathology
  • Mycobacterium abscessus / isolation & purification
  • Myelodysplastic Syndromes / etiology
  • Peripheral Blood Stem Cell Transplantation
  • Pulmonary Embolism / etiology
  • Skin Ulcer / etiology
  • Warts / etiology
  • Young Adult

Substances

  • GATA2 Transcription Factor