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: The proband is a 38-year-old Caucasian male, who presented with progressive dyspnea and fatigue of 3 months duration and was found to have pancytopenia. A bone marrow biopsy revealed hypocellular marrow but demonstrated acute myeloid leukemia (AML) with the following cytogenetic abnormalities: t (1; 21) (q10; q10) /+8/46XY . He received standard induction chemotherapy with idarubicin and cytarabine, and his course was complicated by an orbital fungal infection with Absidia lithemia, medically and surgically managed, following which he underwent a reduced-intensity conditioning-matched unrelated donor allogeneic hematopoietic stem cell transplant (MUD-Allo-HCT). Posttransplant course was complicated by severe refractory immune-mediated thrombocytopenia requiring a splenectomy and an orbital relapse of AML. Due to history of multiple family members being affected (Fig.2) by AML and extra genital warts (sister, son, and daughter), congenital lymphedema (son), and cytopenias (sister) a work-up for familial bone marrow failure syndromes was carried out. GATA2 mutation analysis performed at the National Institutes of Health (NIH) confirmed the presence of a missense mutation (1339A>C, p S447R) in the patient, a female sibling, a son, and a daughter. The female sibling with MDS and viral warts also underwent MUD-Allo-HSCT (hematopoietic stem cell transplant) and remains symptom-free 14 months posttransplant. The probands son and daughter also underwent MUD allogeneic HSCT and are doing very well more than 12 months posttransplant. Patient characteristics and outcomes are shown in Table2.
Affiliation: Penn State Milton S. Hershey Cancer Institute, Hershey, Pennsylvania.