Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia

• Published in: Blood 2000-09, Vol.96 (6), p.2049-2054
• Main Authors: Kojima, Seiji, Hibi, Shigeyoshi, Kosaka, Yoshiyuki, Yamamoto, Masuji, Tsuchida, Masahiro, Mugishima, Hideo, Sugita, Kanji, Yabe, Hiromasa, Ohara, Akira, Tsukimoto, Ichiro
• Format: Article
• Language: English
• Subjects: Adolescent; Anemia, Aplastic - drug therapy; Anemia, Aplastic - immunology; Anemias. Hemoglobinopathies; Antilymphocyte Serum - administration & dosage; Biological and medical sciences; Child; Child, Preschool; Cyclosporine - administration & dosage; Danazol - administration & dosage; Diseases of red blood cells; Drug Therapy, Combination; Estrogen Antagonists - administration & dosage; Female; Granulocyte Colony-Stimulating Factor - administration & dosage; Hematologic and hematopoietic diseases; Humans; Immunomodulators; Immunosuppression; Immunosuppressive Agents - administration & dosage; Infant; Male; Medical sciences; Pharmacology. Drug treatments; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.6.2049

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 μg/m2, 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.