Creutzig Ursula, Zimmermann Martin, Reinhardt Dirk, Dworzak Michael, Stary Jan, Lehrnbecher Thomas
Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer-Str 33, D-48129 Muenster, Germany.
J Clin Oncol. 2004 Nov 1;22(21):4384-93. doi: 10.1200/JCO.2004.01.191.
The rates of early death (ED) and treatment-related mortality (TRM) are unacceptably high in children undergoing intensive chemotherapy for acute myeloid leukemia (AML). Better strategies of supportive care might help to improve overall survival in these children.
In a retrospective study, we analyzed incidence, clinical features, and risk factors for lethal complications of 901 children enrolled onto the multicenter trials Acute Myeloid Leukemia-Berlin-Frankfurt-Muenster (AML-BFM) 93 and AML-BFM 98.
One hundred four patients (11.5%) enrolled onto the clinical trials AML-BFM 93 and AML-BFM 98 died shortly after diagnosis or as a result of treatment-related complications. Thirty-two patients (3.5%) died before (six patients) or during (26 patients) the first 14 days of treatment, mainly as a result of bleeding or leukostasis. Low performance status, hyperleukocytosis, and French-American-British type M5 were the main risk factors for a lethal event before day 15. After day 15, the predominant causes of death were complications caused by infections, particularly bacterial and fungal infections. The incidence of lethal infections was highest during induction therapy and decreased thereafter. When comparing both clinical trials, significantly fewer patients died within the first 6 weeks in AML-BFM 98 than in AML-BFM 93 (14 [3.5%] of 430 patients v 35 [7.4%] of 471 patients; P = .01).
To reduce the high incidence of ED and TRM in children with AML, early diagnosis and adequate treatment of complications are needed. Children with AML should be treated in specialized pediatric cancer centers only. Prophylactic and therapeutic regimens for better treatment management of bleeding disorders and infectious complications have to be assessed in future trials to ultimately improve overall survival in children with AML.
接受强化化疗的急性髓系白血病(AML)患儿的早期死亡(ED)率和治疗相关死亡率(TRM)高得令人难以接受。更好的支持性护理策略可能有助于提高这些患儿的总体生存率。
在一项回顾性研究中,我们分析了901名参加多中心试验急性髓系白血病-柏林-法兰克福-明斯特(AML-BFM)93和AML-BFM 98的患儿发生致命并发症的发生率、临床特征及危险因素。
参加AML-BFM 93和AML-BFM 98临床试验的104例患者(11.5%)在诊断后不久或因治疗相关并发症死亡。32例患者(3.5%)在治疗的前14天内(6例)或治疗期间(26例)死亡,主要原因是出血或白细胞淤滞。体能状态差、白细胞增多症及法美英(FAB)分型M5是第15天前发生致命事件的主要危险因素。第15天后,主要死亡原因是感染引起的并发症,尤其是细菌和真菌感染。致命感染的发生率在诱导治疗期间最高,之后下降。比较两项临床试验时,AML-BFM 98中在前6周内死亡的患者明显少于AML-BFM 93(430例患者中有14例[3.5%],471例患者中有35例[7.4%];P = 0.01)。
为降低AML患儿的高ED率和TRM,需要早期诊断并充分治疗并发症。AML患儿应仅在专业儿科癌症中心接受治疗。未来试验必须评估用于更好地治疗出血性疾病和感染性并发症的预防和治疗方案,以最终提高AML患儿的总体生存率。