title: Successful treatment with allogenic hematopoietic stem cell transplantation of a severe congenital neutropenia patient harboring a novel ELANE mutation.
abstract: We report a 4-year-old boy with severe congenital neutropenia (SCN), who was successfully treated with hematopoietic stem cell transplantation (HSCT). The patient had frequently developed bacterial infections since 6 months of age, and showed severe neutropenia below 100/μl at 1 year and 4 months of age. The patient harbored a heterozygous missense mutation in ELANE exon 3 (p.Q73P, g.2253 A>C). This was a novel de novo mutation, and he was thus diagnosed as having SCN. Because of failure to respond to granulocyte colony-stimulating factor treatment and repeated admissions due to bacterial infections, allogeneic HSCT was performed from a serologically matched unrelated donor following the conditioning regimen: fludarabine/melphalan/anti-thymocyte globulin and a low dose of total body irradiation. Tacrolimus and a short course of methotrexate were used for graft-versus-host disease prophylaxis. Engraftment was achieved at day 12, and the patient maintained normal hematopoiesis for over 15 months after HSCT. We concluded that HSCT is a useful treatment for SCN patients, especially those who are at high risk for leukemic transformation. However, a larger number of SCN patients and longer follow-up are necessary to identify appropriate conditioning regimens and long-term prognosis.
authors.affiliation: Department of Pediatrics, Nishi-Kobe Medical Center.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawaguch
authors.forename: Kousaku
authors.initials: K
authors.lastname: Matsubara
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Uchida
authors.forename: Atsuro
authors.initials: A
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Miyata
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Hasegawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kosaka
authors.forename: Aya
authors.initials: A
authors.lastname: Iwata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nigami
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D064591:Allografts; D000080984:Congenital Bone Marrow Failure Syndromes; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007223:Infant; D019272:Leukocyte Elastase / Q000235:genetics*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D020125:Mutation, Missense; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics / Q000628:therapy; D016559:Tacrolimus / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D019272:Leukocyte Elastase; D016559:Tacrolimus; D008727:Methotrexate