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

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.

Germline predisposition in myeloid neoplasms: Unique genetic and clinical features of GATA2 deficiency and SAMD9/SAMD9L syndromes

“…HSCT was shown to reverse HPV-related lesions as well respiratory problems (PAP) [ 68 , [103] , [104] , [105] ]. Patients with stable disease course, without relevant infections, bone marrow dysplasia and transfusion-dependency might qualify for a watch & wait strategy [ 106 , 107 ]. However, it can be assumed that most GATA2-deficient patients show progressive disease and even with careful watching the best opportunity for low risk HSCT might be missed.…”

GATA2 deficiency and haematopoietic stem cell transplantation: challenges for the clinical practitioner

“…Severe infections need to be treated properly before proceeding to HSCT because highly inflammatory states form an inhospitable environment for donor HSCs. Still, at present, there are no consensus guidelines regarding the optimal timing, conditioning regimen, donor source and antimicrobial prophylaxis for HSCT (Parta et al , ; Simonis et al , ). The European Working Group on Childhood Myelodysplastic Syndromes (EWOG‐MDS) guidelines partly meet those needs by providing recommendations for germline GATA2 screening and HSCT in paediatric and young adult patients with MDS/AML and unfavourable genetic alterations (e.g.…”

“…First, although matched related donors remain the first choice, haploidentical HSCT using an adjusted conditioning regimen and PTCy has proven to be an effective alternative to matched-donor HSCT with similar survival rates and lower grade GVHD (Parta et al, 2018;Hickstein, 2018). Second, bone marrow stem cells are preferred over peripheral blood stem cells, and umbilical cord blood is to be avoided (Parta et al, 2018;Simonis et al, 2018). Third, intensive but non-myeloablative conditioning regimens have been successful (Parta et al, 2018;Simonis et al, 2018).…”

When should transplant physicians think about familial blood cancers?

“…There have also been several reports of patients with GATA2 deficiency syndrome who underwent successful HCT prior to the HM development . Tholouli et al described three patients, ranging in age from 12 to 34 years, with a history of recurrent severe infections and pathogenic germline GATA2 mutations that underwent HCT from a MUD .…”