GATA2 deficiency syndrome is an inherited immune and bone marrow failure disorder with predisposition to myeloid malignancies. Allogeneic hematopoietic cell transplantation (allo-HCT) is a potential curative treatment. However, patients usually enter transplant with significant comorbidities, rendering them at a high risk for early transplant complications. Available reports on outcomes following HCT are scarce.
The Center for International Blood and Marrow Transplant Research (CIBMTR) registry was used to evaluate outcomes of patients with GATA2 deficiency who received allo-HCT. Primary outcome was overall survival (OS) at 1 and 3 years post-HCT. Causes of death were described. Frequency of acute graft-versus-host disease (aGVHD) and cumulative incidence of chronic GVHD (cGVHD) was assessed. Regression analysis was performed to determine factors associated with developing aGVHD and cGVHD.
To evaluate outcomes of patients with GATA2 deficiency who received allo-HCT.
We identified 127 patients that received allo-HCT at 46 centers (median age 23 years [0.7-61]; 63% were adults). Most (64%) had a high comorbidity index (HCT-CI >3) with infection (40%), prior solid tumor (35%), and moderate/severe pulmonary disease (26%) being the most common comorbidities. Immune deficiency and bone marrow failure were the indications for transplant in 76% of patients, with the remaining indication being myelodysplastic syndrome (MDS) or leukemia. Most received myeloablative conditioning regimen (76%) and received HCT from unrelated donors (56%). The median follow-up was 4 years (0.3-12 years). OS was 93% (95% confidence interval [CI] 89-97%) at 1 year and 82% (95% CI 77-91%) at 3 years. OS didn’t differ when stratifying for age or transplant indication. Main cause of death was organ failure followed by infection. Subgroup analysis of 40 patients with post-HCT infectious data showed a high frequency of post-HCT infectious complications (87%), the majority being viral (67%). Endothelial complications (transplant-associated thrombotic microangiopathy [TA-TMA; 2%] and veno-occlusive disease [VOD; 5%]) were rare. All patients had primary engraftment. GVHD was frequently observed post-HCT: 60% of patients developed aGVHD, of which 60% were grade II-IV; cumulative incidence of cGVHD was 44% (95% CI 34-54%) at 1 year, with the majority (84%) experiencing extensive disease. GVHD was a contributing cause of death in 6 patients. Regression analysis did not identify any variables that significantly affected development of GVHD.
In patients with GATA2 deficiency, mortality related to transplant was low. However, the incidence of GVHD was high, adding to post-HCT–related morbidity. Future research should be directed toward assessing risk factors for GVHD and optimizing prevention strategies.
