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Effective preventive central nervous system therapy with extended triple intrathecal therapy and the modified ALL‐BFM 86 chemotherapy program in an enlarged non‐high risk group of children and adolescents with non‐B‐cell acute lymphoblastic leukemia
Author(s) -
Stark Batia,
Sharon Rivka,
Rechavi Gideon,
Attias Dina,
Ballin Ami,
Cividalli Gabriel,
Burstein Yoav,
Sthoeger Dalia,
Abramov Ayala,
Zaizov Rina
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000101)88:1<205::aid-cncr28>3.0.co;2-7
Subject(s) - medicine , etoposide , chemotherapy , radiation therapy , context (archaeology) , cumulative incidence , pediatrics , surgery , cohort , paleontology , biology
BACKGROUND Preventive cranial radiotherapy (CRT) in childhood acute lymphoblastic leukemia (ALL), although effective, may be associated with neurologic sequelae and second malignancies. Attempts to replace CRT with intensified intrathecal therapy (IT) have shown promise in lower risk subgroups. In the Israel National Study (INS) 89 trial, the efficacy of extended triple IT (TIT) alone for cranial prophylaxis in an enlarged non‐high risk group (Non‐HRG) was assessed in the context of a modified ALL‐Berlin–Frankfurt–Munster (BFM) systemic chemotherapy program. METHODS Non‐HRG patients included the standard‐risk group (SRG) and the risk group (RG), as defined in ALL‐BFM 86. In the INS 89 protocol, all Non‐HRG patients were treated with extended TIT × 18 times and systemic therapy based on the BFM 86 protocol, with the addition of etoposide × 4 times. The HRG patients, classified according to BFM 86 criteria, were treated with the BFM 90 HRG protocol including CRT. RESULTS A total of 250 patients were enrolled. At a median follow‐up of 58 months (range, 2–8.5 years), the overall 5‐year event free survival (EFS) was 73.5% ± 3% (standard error [SE]), and the cumulative central nervous system (CNS) recurrence rate was 4.3% ± 1.4% (SE) (isolated, 2.3%; combined, 2%). Of the 220 eligible children, 189 (86%) were in the Non‐HRG group, and their 5‐year EFS was 77.8% ± 3% (SE). The cumulative CNS recurrence rate for patients without CNS disease at presentation was 3.1% ± 1% (SE) (isolated, 1.7%; combined, 1.4%). Within the risk subsets defined by the BFM 86 of the Non‐HRG, the 5‐year EFS rates of the RG (148 patients) and the SRG (41 patients) were 74.8% ± 4% (SE) and 89.5% ± 5% (SE), respectively, and the rates of CNS recurrence (isolated and combined) were 4% and 0%, respectively. For the HRG (31 patients), the 5‐year EFS and CNS recurrence rates were 47.9% ± 9% (SE) and 8.5% ± 6% (SE), respectively. CONCLUSIONS Early extended TIT therapy in the context of modified BFM 86 systemic chemotherapy was found to provide adequate CNS protection and systemic leukemia control in patients with nonhigh risk ALL. However, no benefit for etoposide could be proven in this study. Cancer 2000;88:205–16. © 2000 American Cancer Society.