RANDOMIZED COMPARISON OF ROTATIONAL CHEMOTHERAPY IN HIGH-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA OF CHILDHOOD - FOLLOW-UP AFTER 9 YEARS

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 combinatio n 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 g iven continuation chemotherapy of oral 6-mercaptopurine and methotrexa te until 2 years after the date of diagnosis. The 9-year event-free su rvival (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, 11/10 0 patients were not in sro remission at day 28 opposed to 7/101 patien ts in the SR group. Children aged < 1 year (6/6 relapses) or aged grea ter than or equal to 10 years had a worse prognosis (EFS 64% +/- 5% vs . 77% +/- 4% in patients 1-10 years old). After 5 years EFS was inferi or in the RR group attributable to a significantly higher relapse rate in children with a WBC greater than or equal to 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 w ith early intensive therapy and rotation of different drug combination s offers long-term disease-free survival for children with high-risk A LL. A continuous 4-week exposure to one drug combination may be necess ary to achieve optimal results, especially in children with a high leu kaemic cell burden.