Spectrum of myeloid neoplasms and immune deficiency associated with germline GATA2 mutations.
Bottom Line: Allogeneic stem cell transplant remains the treatment of choice.Morbidity, mortality, and social costs due to the familial nature of the disease are considerable.We describe our experience with the disorder in three affected families and a comprehensive review of current literature.
Affiliation: Penn State Milton S. Hershey Cancer Institute, Hershey, Pennsylvania.Show MeSH
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Mentions: Allogeneic HCT remains the only treatment with favorable responses in GATA2-mutated MDS/AML (Fig.3). In the NIH experience, 21 patients were transplanted for either hematological (MDS/AML) or immunological indications (age 15–49 years) with good responses (Fig.1). Of note, half the patients who were not transplanted passed away by age 40 51. A similar NIH experience further outlined use of conditioning regimens for nonmyeloablative allogeneic HCT 66. Donors included fully matched related and unrelated donors (conditioning-fludarabine + total body radiation 200 cGy) and alternative sources such as umbilical cord blood and haploidentical bone marrow (fludarabine + cyclophosphamide and total body irradiation 200 cGy, with posttransplant cyclophosphamide for T-cell replete grafts). Busulfan was later added for a more robust eradication of the GATA2 clone. Azithromycin was started before and continued for 1 year posttransplant due to increased propensity to nontuberculous mycobacterial (NTM) infections, in addition to standard prophylaxis. No NTM infections during or after transplant were reported using prophylaxis. Overall survival was 57% at 36 months. Our patient characteristics and outcomes are shown in Table2. Tacrolimus was used for graft versus host disease prophylaxis. All four patients have engrafted with 100% donor chimerisms (CD3 and CD33 fractions). One patient had CMV-Cytomegalovirus reactivation and refractory thrombocytopenia which failed to improve despite splenectomy. Three developed acute GVHD and one had chronic GVHD involving esophagus with dysphagia and strictures that improved with steroids.
Affiliation: Penn State Milton S. Hershey Cancer Institute, Hershey, Pennsylvania.