title: Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents.
abstract: The prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined. Children 21 years old or younger with newly diagnosed B-cell non-Hodgkin lymphoma/B-cell acute lymphoblastic leukemia (B-NHL/B-ALL) with higher risk factors (bone marrow [BM] with or without CNS involvement) were randomized to standard intensity French-American-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 g/m2) plus extra intrathecal therapy. Fifty-one percent had BM involvement, 20% had CNS involvement, and 29% had BM and CNS involvement. One hundred ninety patients were randomized. The probabilities of 4-year event-free survival (EFS) and survival (S) were 79% +/- 2.7% and 82% +/- 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reduced-intensity therapy, the 4-year EFS after randomization was 90% +/- 3.1% versus 80% +/- 4.2% (one-sided P = .064) and S was 93% +/- 2.7% versus 83% +/- 4.0% (one-sided P = .032). Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide, Oncovin [vincristine], prednisone (COP) reduction therapy had a significantly inferior EFS and S (P < .001). Standard-intensity FAB/LMB therapy is recommended for children with high-risk B-NHL (B-ALL with or without CNS involvement).
authors.affiliation: Morgan Stanley Children's Hospital of New York-Presbyterian, Columbia University, New York, NY 10032, USA. mc1310@columbia.edu
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
authors.forename: Mary
authors.initials: M
authors.lastname: Gerrard
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Anne
authors.initials: A
authors.lastname: Auperin
authors.forename: C Ross
authors.initials: CR
authors.lastname: Pinkerton
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
authors.forename: Claire
authors.initials: C
authors.lastname: Weston
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.forename: Martine
authors.initials: M
authors.lastname: Raphael
authors.forename: Keith
authors.initials: K
authors.lastname: McCarthy
authors.forename: Catherine
authors.initials: C
authors.lastname: Patte
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000401:mortality; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000401:mortality; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D012307:Risk Factors; D015996:Survival Rate; D017211:Treatment Failure