Germline heterozygous GATA2 mutations causing GATA2 deficiency are characterized by a broad phenotypic spectrum including cytopenias, severe bacterial, viral and nontuberculous mycobacterial infections, myelodysplasia and myeloid leukemias, pulmonary alveolar proteinosis, and lymphedema. The only curative treatment is allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Based on our experience with three cases, we address the difficulties often faced by clinicians in this extraordinary syndrome that was only identified in 2011.
Hematological, immunological and genetic analyses were performed.
Three GATA2-deficient patients were diagnosed in our center. All had MDS/AML and low monocyte, B-cell, NK-cell and dendritic cell counts. Two patients also had severe infections. Unfortunately, there are no guidelines regarding the optimal timing, conditioning regimen, donor source and antimicrobial prophylaxis for HSCT. Patient 1, a female, is doing well under immunoglobulin replacement therapy nine years after chemotherapy for AML, without HSCT. Patients 2 and 3, males, both underwent allo-HSCT because of life-threatening infections and MDS, but using different conditioning regimens and donor types. Patient 2 suffered from severe chronic GVHD and died four years post-transplant from ischemic heart disease. Patient 3 was transplanted using more intensive non-myeloablative conditioning, and is currently doing well two years post-transplant.
Furthermore, mutation analysis of GATA2 turned out to be technically cumbersome. In one patient, intensive screening for mutations was negative and was only found through array-CGH.
Although there are still challenges in clinical practice that need to be overcome, increasing experience in transplanting these patients has gained insight on optimal donor and stem cell source and conditioning.