Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation

In this population-based material from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2860 children below 15 years of age w ere diagnosed with acute lymphoblastic leukemia (ALL) from July 1981 to Jun e 1998. The annual incidence was 3.9/100000 children and was stable through out the study period. The development from regional or national protocols t o common Nordic treatment protocols for all risk groups was completed in 19 92 through a successive intensification with multidrug chemotherapy, includ ing pulses of methotrexate in high doses and avoidance of cranial irradiati on in most children. The overall event-free survival (EFS) at 5 years has i ncreased from 56.5 +/- 1.7% in the early 1980s to 77.6 +/- 1.4% during the 1990s. The main improvements were seen in children with non-high risk leuke mia. In high-risk patients, progress has been moderate, especially in child ren with high WBC (greater than or equal to 100 x 10(9)/l) at diagnosis. Du ring the last time period (January 1992-June 1998), only 10% of the patient s have received cranial irradiation in first remission, while 90% of the pa tients have received pulses of high dose methotrexate (5-8 g/m(2)) isolated or combined with high-dose cytosine arabinoside (total dose 12 g/m(2)) plu s multiple intrathecal injections of methotrexate as CNS-targeted treatment , not translating into increased cumulative incidence of CNS relapse.