Sporadic or familial germline mutations in GATA2 frequently result in a bone marrow failure syndrome characterized by recurrent life-threatening infections, cytopenias, and progression to myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), or chronic myelomonocytic leukemia (CMML). Hematopoietic stem cell transplantation (HSCT) represents the only definitive therapy for GATA2 deficiency. However, the highly variable disease penetrance in different families, and in mutation positive individuals within a single family, make the timing of HSCT challenging. We assessed the utility of scoring patient characteristics according to the Revised International Prognostic Scoring System (IPSS-R) to predict survival after HSCT in a cohort of 51 patients with GATA2 deficiency who had progressed to MDS. Higher IPSS-R scores significantly correlated with reduced overall survival after transplant. In evaluating the components of the IPSS-R score for patients with GATA2 deficiency, cytopenias, including anemia, neutropenia, and thrombocytopenia, were important variables in placing these patients in higher risk IPSS-R categories. Since GATA2 deficiency patients have very low peripheral blood monocyte, B cell, and NK cell counts, we evaluated these cytopenias in conjunction with IPSS-R scoring. These cytopenias also had prognostic value for outcome after HSCT in patients with GATA2 deficiency. Cytogenetics, another component of the IPSS-R score, also placed patients with GATA2 deficiency into higher risk categories. In particular, patients harboring monosomy 7 had poorer survival outcomes than patients with normal cytogenetics or trisomy 8. Of note, all five patients with GATA2 deficiency and trisomy 1q successfully underwent HSCT. Clonal cytogenetic progression with the development of additional cytogenetic aberrations was a harbinger of myeloid progression and led to HSCT. In a cohort of four patients who underwent HSCT following progression to AML/CMML, there was only one survivor. Thus, HSCT is recommended in patients with GATA2 deficiency and intermediate or high-risk IPSS-R scores before the development of AML or CMML.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.