Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: Results of study Acute Myeloid Leukemia - Berlin-Frankfurt-Munster 93

Purpose: To improve outcome in high-risk patients, high-dose cytarabine and mitoxantrone (HAM) was introduced into the treatment of children with acut e myelogenous leukemia (AML) in study AML-BFM 93. patients were randomized to HAM as either the second or third therapy block, for the purpose of eval uation of efficacy and toxicity. Patients and Methods: A total of 471 children with de novo AML were entered onto the trial; 161 were at standard risk and 310 were at high risk. After the randomized induction (daunorubicin v idarubicin), further therapy, wit h the exception of HAM, was identical in the two risk groups and also compa rable to that in study Acute Myeloid Leukemia-Berlin-Frankfurt-Munster (AML -BFM) 87. Results: Overall, 387 (82%) of 471 patients achieved complete remission, an d 5-year survival, event-free survival (EFS), and disease-free survival rat es were 60%, 51%, and 62%, respectively. Idarubicin induction resulted in a significantly better blast cell reduction in the bone marrow on day 15. Es timated survival and probability of EFS were superior in study AML-BFM 93 c ompared with study AML-BFM 87 (P = .01, log-rank test). This improvement, h owever, was restricted to the 310 high-risk patients (remission rate and pr obability of 5-year EFS in study AML-BFM 93 v study AML-BFM 87: 78% v 68%, P = .007; and 44% v 31%, P = .01, log-rank test). Probability of 5-year EFS among standard-risk patients in study AML-BFM 93 was similar to that in st udy AML-BFM 87 (65% v 63%, P = not significant). Whether HAM was placed as the second or third therapy block was of minor importance. However, patient s who received the less intensive daunorubicin treatment during induction b enefited from early HAM. Conclusion: Improved treatment results in children with high-risk AML in st udy AML-BFM 93 must be attributed mainly to the introduction of HAM. (C) 20 01 by American Society of Clinical Oncology.