Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group

• Published in: Blood Vol. 101; no. 10; pp. 3809 - 3817
• Main Authors: Bostrom, Bruce C., Sensel, Martha R., Sather, Harland N., Gaynon, Paul S., La, Mei K., Johnston, Katherine, Erdmann, Gary R., Gold, Stuart, Heerema, Nyla A., Hutchinson, Raymond J., Provisor, Arthur J., Trigg, Michael E.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-05-2003; The Americain Society of Hematology
• Subjects: Administration, Oral; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; Biological and medical sciences; Blood Cell Count; Chemotherapy; Child; Child, Preschool; Dexamethasone - administration & dosage; Dexamethasone - adverse effects; Dexamethasone - therapeutic use; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Humans; Infant; Injections, Intravenous; Injections, Spinal; Karyotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Mercaptopurine - administration & dosage; Mercaptopurine - adverse effects; Mercaptopurine - therapeutic use; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Pharmacology. Drug treatments; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Prednisone - administration & dosage; Prednisone - adverse effects; Prednisone - therapeutic use; Human; Antineoplastic agent; Corticosteroid; Purine derivatives; Dexamethasone; Intravenous administration; Steroid hormone; Acute; Oral administration; Administration schedule; Prednisone; Malignant tumor; Chemotherapy; Treatment; Antimetabolic; Weekly; Adrenal hormone; Clinical trial; Acute lymphocytic leukemia; Daily dose; Therapeutic protocol; Child; Comparative study; Mercaptopurine
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-08-2454

Conventional therapy for childhood acute lymphoblastic leukemia (ALL) includes prednisone and oral 6-mercaptopurine. Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous (IV) over oral 6-mercaptopurine, which remain to be validated. We report the results of a randomized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine. Children with National Cancer Institute standard-risk ALL were randomly assigned in a 2 × 2 factorial design to receive dexamethasone (6 mg/m2/d) for 28 days in induction, plus taper, compared with prednisone (40 mg/m2/d). The second randomized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation. During maintenance, 5 days of the randomized steroid was given monthly, at the same dose, and all patients received daily oral 6-mercaptopurine. During delayed intensification, all patients received a dexamethasone dosage of 10 mg/m2/d for 21 days, with taper. Intrathecal (IT) methotrexate was the sole central nervous system–directed therapy. Patients randomly assigned to receive dexamethasone had a 6-year isolated central nervous system–relapse rate of 3.7% ± 0.8%, compared with 7.1% ± 1.1% for prednisone (P = .01). There was also a trend toward fewer isolated bone marrow relapses with dexamethasone. The 6-year event-free survival (EFS) was 85% ± 2% for dexamethasone and 77% ± 2% for prednisone (P = .002). EFS was similar with oral or IV 6-mercaptopurine; however, patients assigned to IV 6-mercaptopurine had decreased survival after relapse.