[Analysis of causes of death during intensive chemotherapy according to treatment protocol AML-BFM 93]

During intensive chemotherapy for AML, more than 10% of patients die because of treatment complications but not because of progression of their underlying disease. In order to improve supportive care and to decrease mortality, we analysed the causes of death and their relationship to the cycles of chemotherapy in children undergoing treatment for AML according to the study AML-BFM 93.

Thirty-five (7.4%) of a total of 471 patients treated according to protocol AML-BFM 93 died before or within the first 6 weeks after diagnosis (early death). Fourty-nine patients (10%) did not achieve remission, and 18 (4 %) died of therapy-related complications after having achieved remission. In comparison to earlier AML-BFM studies, early mortality was reduced from 13%, 12%, 9% (AML-BFM 78, 83, 87) to 7% (AML-BFM 93, p-trend = 0.03). In contrast, mortality of patients in complete continuous remission (CCR) did not change. Infectious complications, in particular due to bacterial and fungal pathogens, were the main cause of death. One patient died of arrhythmia associated with SIAD. After stem-cell transplantation in first remission, 7 of 51 patients died, mainly because of graft-versus-host-disease and/or infections. The incidence of infectious complications decreased with the number of chemotherapy cycles and was highest during induction therapy. Fatal complications occurred in one patient during maintenance therapy and in one patient thereafter; both patients were in CCR. Another 14 patients died during intensive therapy (before day 150) mostly with a low percentage of blasts, but no haematologic recovery. The cause of death in these children was mainly bacterial infection or invasive aspergillosis, but seldom progression of leukaemia.

This analysis confirmed the high incidence of fatal infections in children with AML during chemotherapy-induced severe neutropenia. To increase overall survival in children undergoing therapy for AML, we propose (1) to improve the prophylactic and therapeutic measures for haemorrhage and infections, (2) to continue risk-adapted therapy and (3) to treat high-risk patients in specialised centres only.