Creutzig U, Zimmermann M, Reinhardt D, Lehrnbecher T
Pädiatrische Hämatologie/Onkologie, Universitäts-Kinderklinik Münster.
Klin Padiatr. 2003 May-Jun;215(3):151-8. doi: 10.1055/s-2003-39374.
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.
在急性髓系白血病（AML）的强化化疗期间，超过10%的患者死于治疗并发症而非基础疾病进展。为了改善支持治疗并降低死亡率，我们根据AML-BFM 93研究分析了接受AML治疗的儿童的死亡原因及其与化疗周期的关系。
按照AML-BFM 93方案治疗的471例患者中，35例（7.4%）在诊断前或诊断后前6周内死亡（早期死亡）。49例患者（10%）未达到缓解，18例（4%）在达到缓解后死于治疗相关并发症。与早期的AML-BFM研究相比，早期死亡率从13%、12%、9%（AML-BFM 78、83、87）降至7%（AML-BFM 93，p趋势=0.03）。相比之下，完全持续缓解（CCR）患者的死亡率没有变化。感染并发症，尤其是由细菌和真菌病原体引起的，是主要死亡原因。1例患者死于与抗利尿激素分泌异常综合征相关的心律失常。首次缓解后进行干细胞移植的51例患者中，7例死亡，主要原因是移植物抗宿主病和/或感染。感染并发症的发生率随着化疗周期数的增加而降低，在诱导治疗期间最高。1例患者在维持治疗期间死亡，另1例在维持治疗后死亡；两名患者均处于CCR状态。另外14例患者在强化治疗期间（第150天之前）死亡，大多数患者原始细胞比例较低，但没有血液学恢复。这些儿童的死亡原因主要是细菌感染或侵袭性曲霉病，但很少是白血病进展。
该分析证实了AML患儿在化疗引起的严重中性粒细胞减少期间致命感染的高发生率。为了提高接受AML治疗儿童的总体生存率，我们建议：（1）改善出血和感染的预防及治疗措施；（2）继续进行风险适应性治疗；（3）仅在专科中心治疗高危患者。
