Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92

The German Go-operative Study Group COALL far treatment of acute lymphoblas tic leukemia (ALL) in childhood started the first trial in 1980. This repor t gives an overview of the long-term results of the four consecutive studie s COALL-82, COALL-85, COALL-89 and COALL-92. Besides improvement in long-te rm survival major objectives were reduction of treatment-related toxicity b y transferring asparaginase (ASP) from induction therapy to intensive phase and omitting CNS irradiation by stepwise increase of the initial white blo od count (WBC) up to 50 x 10(9)/1 (exception T-ALL) as criterion for irradi ation. In study COALL-85 in high risk patients slow vs rapid rotational tre atment was randomized. In study COALL-92 initial response to daunorubicin ( DNR) as a l-h vs 24-h infusion and its prognostic value was investigated. F urthermore, g-mercaptopurine (6-MP) and B-thioguanine (6-TG) were randomize d in maintenance treatment. In total, 1191 eligible patients were enrolled. Induction treatment without ASP has been shown to be as effective and less hazardous than the former four-drug induction. CNS control could be obtain ed in most without cranial irradiation (CNS relapse-free survival >95%). Th e leukemic cell kill with a 24-h DNR infusion was equivalent to that of a l -h infusion. DNR response was of less prognostic significance than predniso ne response. The rapid rotation regimen failed to improve outcome as well a s 6-TG in maintenance treatment. However, intensification of systemic treat ment resulted in an increase in overall event-free survival (EFS) to approx imately 80% which is comparable to other groups.