[Combination of radio-chemotherapy for curing of childhood hematologic tumors: preventive approaches and problems on CNS involvement]

Abstract

The CNS has often been classified as a "drug sanctuary" as most anticancer drugs do not achieve effective penetration of the blood-brain barrier. With more effective systemic chemotherapy program, the incidence of CNS involvement in leukemia has increased. The strategy for treatment of leukemia is that one achieves by destruction of all leukemia cells including CNS. Between 1972 and 1978, 153 children with ALL were treated with multiple methods of CNS-prophylaxis and were analyzed in relation to treatment regimens, age, sex and initial hematologic status. Patients received CNS-prophylaxis; Group I: three doses of intrathecal methotrexate (MTX) and hydrocortisone (HDC), Group II: same as in Group I followed by cyclic MTX and HDC, Group III: same as in Group I plus 2,400 cGy of cranial irradiation. CNS leukemia terminated complete remission in 25 of 153 patients (16.3%). The cumulative incidence of CNS leukemia at 4-year calculated by the Kaplan-Meier Method was 40.5% in Group I, 26.9% in Group II, and 14.5% in Group III. We concluded that the combination of cranial irradiation and intrathecal MTX and HDC was highly efficacious. The efficacy of high-dose MTX with CF rescue therapy for CNS-prophylaxis was evaluated in 62 children with ALL between 1978 and 1980 (protocol 787 study), and was demonstrated to be same as cranial irradiation in standard risk of ALL. In protocol 811 study (1981-1984), the dosage of cranial radiation has been reduced from 2,400 cGy to 1,800 cGy without loss of efficacy for CNS-prophylaxis. Although CNS-leukemia was no longer an unmanageable clinical problem, and the prospects for cure of ALL appeared good, there remained question as to the toxic effects of intensive treatment on the CNS. Successful prevention of these complications will depend in large part on an understanding of their causes.