Donor-derived myelodysplastic syndrome after allogeneic stem cell transplantation in a family with germline GATA2 mutati
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CASE REPORT
Donor‑derived myelodysplastic syndrome after allogeneic stem cell transplantation in a family with germline GATA2 mutation Naoki Sakata1 · Munehiro Okano1 · Ryujin Masako1 · Ai Tanaka1 · Yuhei Yamashita1 · Takahiro Karasuno2 · Ken‑Ichi Imadome3 · Mitsuru Okada1 · Keisuke Sugimoto1 Received: 23 April 2020 / Revised: 12 August 2020 / Accepted: 23 August 2020 © Japanese Society of Hematology 2020
Abstract Germline GATA2 heterozygous mutations were identified as complex immunodeficiency and hematological syndromes characterized by cytopenia (monocytes, B-cells, NK-cells), susceptibility to mycobacterium, fungus, or Epstein–Barr virus (EBV) infection, and myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) development. Herein, we report a patient with AML who had a fatal infection after allogeneic hematopoietic stem cell transplantation (HSCT) due to impaired immune reconstitution associated with GATA2 mutation. A 15-year-old man was diagnosed with AML with monosomy 7. His family history was negative for immunodeficiency and hematological disorders. He attained complete remission after HSCT from an HLA-identical sister. Post-HSCT examinations performed 15 months later revealed pancytopenia, especially monocytopenia and the absence of B and NK cells, resulting in the occurrence of donor-type MDS. Twenty-one months after HSCT, he developed central nervous system aspergillosis and finally died of the disease. Two months later (24 months after PBSCT), the donor was diagnosed with persistent EBV infection accompanied by MDS with multilineage dysplasia. Genetic analysis of GATA2 revealed a novel heterozygous mutation (c.1023_1026dupCGCC) in both siblings. GATA2 mutations were highly prevalent among adolescent MDS/AML patients with monosomy 7. Therefore, the screening of GATA2 mutations in relatives is necessary when performing HSCT from a relative donor. Keywords Germline GATA2 mutation · Poor outcome · Allogeneic hematopoietic stem cell transplantation · Family donor
Introduction In 2011, germline Guanine-adenine–thymine-adenine 2 (GATA2) heterozygous mutations were identified as the cause of four clinical syndromes: monocytopenia and mycobacterial infection (MonoMac syndrome) [1, 2]; the Emberger syndrome characterized by lymphedema and deafness [3]; dendritic cell, monocyte, B, and NK lymphoid (DCML) deficiency [4]; and familial myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) [5]. There * Naoki Sakata [email protected] 1
Department of Pediatrics, Kindai University Faculty of Medicine, 377‑2, Ohno‑Higashi, Osaka‑Sayama, Osaka 589‑8511, Japan
2
Department of Hematology, Rinku General Medical Center, Izumisano, Japan
3
Department of Advanced Medicine for Infections, National Center for Child Health and Development, Tokyo, Japan
was an overlap among the clinical features of these four clinical syndromes; however, these syndromes are now recognized as a single genetic disorder with protean disease manifestation [3, 5–8]. GATA2 mutations result in loss of function
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