CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA IN THE NETHERLANDS - RANDOMIZED STUDIES AND NATIONWIDE TREATMENT RESULTS FROM 1972 TO 1995

The Dutch Childhood Leukemia Study Group (DCLSG) has implemented eight protocols for the treatment of childhood acute lymphoblastic leukemia (ALL) (ALL I to VIII) during the period from 1972 to 1995. They were based on St. Jude's Total Therapy (ALL II to VI) and the risk-adapted intensive therapy (ALL VII and VIII) developed by the BFM Group, respe ctively, and included seven randomized studies. In study ALT, I (N = 4 3, 1972 to 1973), no effect was observed after the addition of daunoru bicin to vincristine/prednisone pulses during maintenance treatment. I n study ALL II (N = 143, 1973 to 1975) the addition of cyclophosphamid e to maintenance treatment with 6-mercaptopurine/methotrexate increase d toxicity and mortality without increasing the event-free survival ra te. In study ALL III (N = 148; 1975 to 1979) for non-high-risk patient s (defined as initial leukocyte count <50 x 10(9)/L, no initial cental nervous system involvement and no mediastinal mass) no difference was observed in the outcome for patients with or without intermittent vin cristine/ prednisone pulses during maintenance treatment. In study ALL V (N = 240; 1979 to 1984)the addition of daunorubicin to induction tr eatment with vincristine/prednisone/L-asparaginase increased the event -free survival rate at 5 years after diagnosis in non high-risk patien ts (64 +/- 4% versus 55 +/- 5%, respectively; p = 0.047). In the perio d of the nonrandomized study ALL VI (N = 259; 1984 to 1988) for non-hi gh-risk patients cranial irradiation was successfully substituted by i ntensive chemotherapy (dexamethasone, intravenous methotrexate and ear ly and prolonged intrathecal therapy), the event-free survival rate at 5 years was 78 +/- 3%.The results of the three randomized studies in protocol ALL VII and WI are too early to report. Over these two decade s 1,976 children with newly diagnosed ALL were registered, representin g virtually all children with ALL in The Netherlands in this period. T he overall event-free survival rate improved from 4 +/- 2% in 1972 to 1973 to 66 +/- 3% in 1988 to 1991.