Randomized comparison of rotational chemotherapy in high-risk acute lymphoblastic leukaemia of childhood--follow up after 9 years. Coall Study Group.

UNLABELLED: A frequent change of drug combinations may circumvent drug resistance in the treatment of patients with acute lymphoblastic leukaemia (ALL). In study COALL 85/89 201 children with high-risk ALL were randomized to receive over a period of 8 months rotational chemotherapy with six drug combinations given either in slow rotation (SR) (each combination given twice in succession) or in rapid rotation (RR) (each combination given once with a repetition of the drug combinations). Treatment of central nervous system leukaemia consisted of cranial irradiation and intrathecal methotrexate. Both SR and RR treatment groups were then given continuation chemotherapy of oral 6-mercaptopurine and methotrexate until 2 years after the date of diagnosis. The 9-year event-free survival (EFS) rate for the whole group is 69% +/- 3%, and the survival rate 75% +/- 3% at a median follow up of 5.8 years. Failure to achieve remission at day 28 was the most important prognostic factor (EFS 12% +/- 7% vs. 75% +/- 3% in the remission group). In the RR group, 11/100 patients were not in remission at day 28 opposed to 7/101 patients in the SR group. Children aged < 1 year (6/6 relapses) or aged > or = 10 years had a worse prognosis (EFS 64% +/- 5% vs. 77% +/- 4% in patients 1-10 years old). After 5 years EFS was inferior in the RR group attributable to a significantly higher relapse rate in children with a WBC > or = 100/nl. The EFS at 9 years for all patients, however, is similar in both groups (SR 72% +/- 5% vs. RR 67 +/- 5%).
CONCLUSION: The COALL 85/89 treatment protocol with early intensive therapy and rotation of different drug combinations offers longterm disease-free survival for children with high-risk ALL. a continuous 4-week exposure to one drug combination may be necessary to achieve optimal results, especially in children with a high leukaemic cell burden.

RCT Entities:   Population Interventions Outcomes