Journal of Clinical Oncology, Vol 13, 2497-2502, Copyright © 1995 by American Society of Clinical Oncology
Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Munster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica
V Conter, M Arico, MG Valsecchi, C Rizzari, AM Testi, C Messina, PG Mori, R Miniero, R Colella and G Basso
Department of Pediatrics, University of Milano, Italy.
PURPOSE: To assess the effect of treatment intensification and that of
extended intrathecal methotrexate substitution for cranial irradiation in
intermediate-risk acute lymphoblastic leukemia (ALL) children treated with
a Berlin-Frankfurt-Munster (BFM)-based intensive chemotherapy. PATIENTS:
Three hundred ninety-six children with non-B- ALL were enrolled onto the
Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88
study. Standard risk (SR) included patients with low tumor burden (BFM risk
index [RI], < 0.8); intermediate risk (IR) were patients with an RI >
or = 0.8 but less than 1.2; and high risk (HR) were those with an RI >
or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a
modified version of the ALL-BFM 86 study. CNS-directed treatment consisted
of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus
intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally
received extended IT-MTX (nine doses during continuation therapy); cranial
irradiation was given only to HR patients. RESULTS: Of the 375 (94.7%)
children who achieved remission, 1.3% had an adverse event other than
relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE
2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR
patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107
children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5
(6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR
group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2)
overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and
92.3% (2.0) in the HR group. CONCLUSION: Cranial irradiation may be omitted
safely in IR ALL patients treated with BFM-based intensive chemotherapy
when extended intrathecal chemotherapy is given. Because the CNS disease
control was less complete in the SR group, these data challenge the
effectiveness of HD-MTX for protection from CNS disease and support the
protective role of extended intrathecal chemotherapy.
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