title: Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia.
abstract: A prospective multicenter trial of 119 children 1 to 18 years of age with newly diagnosed aplastic anemia (AA) was conducted, comparing treatment using antithymocyte globulin (ATG), cyclosporine (CyA), and danazol (DAN) with or without rhG-CSF (400 microg/m(2), day on days 1-90). All children with very severe AA received rhG-CSF (VSAA group, n = 50). The other children were randomized to receive ATG, CyA, DAN, and rhG-CSF (G-CSF+ group, n = 35) or ATG, CyA, and DAN without rhG-CSF (G-CSF- group, n = 34). After 6 months, the hematologic response rate was 71%, 55%, and 77% in the VSAA group, G-CSF+ group, and G-CSF- group, respectively. There was no difference in the incidence of febrile episodes and documented infections between the G-CSF+ and G-CSF- groups. Bone marrow transplantation (BMT) was attempted in 22 patients in whom initial immunosuppressive therapy (IST; n = 18) failed or in whom a relapse occurred after an initial response (n = 4). Nineteen of the 22 patients are alive and well after a median follow-up of 18 months (range, 3 to 66 months) since BMT. The probability of survival at 4 years was 83% +/- 7% in the VSAA group, 91% +/- 5% in the G-CSF+ group, and 93% +/- 6% in the G-CSF- group. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) developed in one patient in each of the three groups; the overall risk for MDS/AML was 3% +/- 2% at 4 years. Because the results of IST were encouraging, it is suggested that children with AA receive IST as first-line therapy if there is no human leukocyte antigen-matched sibling donor.
authors.affiliation: Japan Childhood Aplastic Anemia Study Group, Nagoya, Japan. kojimas@med.nagoya-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Kojima
authors.forename: S
authors.initials: S
authors.lastname: Hibi
authors.forename: Y
authors.initials: Y
authors.lastname: Kosaka
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Tsuchida
authors.forename: H
authors.initials: H
authors.lastname: Mugishima
authors.forename: K
authors.initials: K
authors.lastname: Sugita
authors.forename: H
authors.initials: H
authors.lastname: Yabe
authors.forename: A
authors.initials: A
authors.lastname: Ohara
authors.forename: I
authors.initials: I
authors.lastname: Tsukimoto
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000276:immunology; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage*; D003613:Danazol / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D004965:Estrogen Antagonists; D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D003613:Danazol