Central nervous system treatment in childhood acute lymphoblastic leukemia. Long-term follow-up of patients diagnosed between 1973 and 1985.
BACKGROUND
Despite advances in the treatment of childhood acute lymphoblastic leukemia (ALL), optimal therapy of the central nervous system (CNS) remains controversial.


METHODS
Between 1973 and 1985, 540 children with ALL (199 standard risk and 341 high risk) were treated on four protocols.


RESULTS
The 7-year event-free survival rate (+/- standard error) was 62.1% (+/- 2.1) for the entire group: 71.8% (+/- 3.2) for standard-risk and 56.4% (+/- 2.7) for high-risk patients. Five hundred eighteen of the children entered complete remission and received cranial irradiation with intrathecal methotrexate for CNS treatment; 197 had standard-risk ALL and 321 had high-risk ALL. Thirty-one patients (5 standard risk and 26 high risk) had a CNS relapse with or without concurrent bone marrow relapse as an initial event, the latest of which was observed 49 months after complete remission. The cumulative incidence of CNS relapse was 6.0% (+/- 1.1) for the entire group: 2.5% (+/- 1.1) for standard-risk and 8.2% (+/- 1.5) for high-risk patients (P = 0.01). CNS recurrence of leukemia, whether as an "isolated" site or a "combined" site of relapse, was a major adverse event. Only 4 of 31 patients were alive for 25+, 28+, 54+, and 71+ months after a CNS relapse. The median survival time after CNS relapse was 22 months: 21 months for the 20 patients who had an isolated CNS relapse, and 23 months for the 11 patients who had a CNS relapse concurrent with a recurrence in other sites.


CONCLUSIONS
Although attempts to diminish CNS treatment-related morbidity are warranted for standard-risk patients, the authors recommend that intensive CNS treatment be enhanced for the high-risk patients because CNS relapses continue to occur in this population. Furthermore, CNS relapse after cranial irradiation was associated with a very poor prognosis and needs to be treated as intensively as a bone marrow relapse.
Division of Biostatics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
R D
RD
Gelber
S E
SE
Sallan
H J
HJ
Cohen
M
M
Donnelly
V
V
Dalton
F
F
Tobia
L A
LA
Clavell
N J
NJ
Tarbell
D001932:Brain Neoplasms / Q000401:mortality / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D008727:Methotrexate / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate
D008727:Methotrexate