Improved treatment results in children with AML: Results of study AML-BFM 93

Background: In the multicenter trial AML-BFM 93 daunorubicin or idarubicin was randomly applied in all patients during induction in combination with c ytarabine and etoposide. After induction all patients were stratified to th e standard or high risk group. To improve outcome in high risk patients hig h dose cytarabine and mitoxantrone (HAM) was introduced. The placing of HAM as either the 2nd or 3rd therapy block was randomized to evaluate the effi cacy and toxicity accordingly. Patients and Methods: 471 children with de n ovo AML entered the trial AML-BFM 93 (161 standard risk, 310 high risk). Re sults: Overall, 387 of 471 (82%) patients achieved remission, 5-year surviv al, event free survival (EFS), and disease free survival were 60% SE 3%, 51 % SE 2% and 62% SE 3%, respectively. Idarubicin-based induction resulted in a significantly better blast cell reduction in the bone marrow on day 15 ( 25 of 144 = 17% patients with >5% blasts compared to 46 of 149 = 31% patien ts after daunorubicin, p chi (2)=0.01). This was, however, mainly seen in h igh risk patients treated with idarubicin (19% vs. 38%, p chi (2)=0.007). C ardiotoxicity, WHO grade 1-3 shortening fraction reduction after induction occurred in 6% patients in both arms. in the total group of patients probab ilities of five years event-free survival and disease-free survival were si milar for patients treated with daunorubicin or idarubicin. However, in pat ients presenting with more than 5% blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (p logrank 0.06). Outcome i n high risk patients was superior in study 93 compared to study 87 (remissi on rate and 5-year pEFS in study AML-BFM 93 vs. study 87: 78% vs. 68%, p = 0.007, and 44% vs. 31%, p, log-rank=0.01). The placing of HAM as the 2nd or 3rd therapy block was of minor importance. However, patients who received the daunorubicin treatment during induction benefited from early HAM. Concl usion: Compared to study AML-BFM 87 treatment results in study AML 93 impro ved significantly in high risk patients. This can partly be contributed to the better response on day 15 after idarubicin induction but is mainly due to the introduction of HAM.