Tomizawa Daisuke, Tabuchi Ken, Kinoshita Akitoshi, Hanada Ryoji, Kigasawa Hisato, Tsukimoto Ichiro, Tsuchida Masahiro
Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
Pediatr Blood Cancer. 2007 Aug;49(2):127-32. doi: 10.1002/pbc.20944.
Various methods of intensive chemotherapy have contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long-term results of the two consecutive trials of Tokyo Children's Cancer Study Group (TCCSG), incorporating repetitive use of high-dose cytarabine (HD-Ara-C) based combination chemotherapy in post-remission phase.
A total of 216 eligible children with newly diagnosed AML were treated in the two consecutive multi-center trials of TCCSG, M91-13 and M96-14, from August 1991 to September 1998. In M91-13 trial, patients received eight courses of intensive post-remission chemotherapy, including six HD-Ara-C containing courses, after remission-induction therapy. Autologous hematopoietic stem cell transplantation (HSCT) could be selected by physician's choice, and allogeneic HSCT was allocated if donor was available. In M96-14 trial, the last two HD-Ara-C courses were omitted from the chemotherapy arm.
The remission-induction rate was 88.8% and probability of 5-year Overall survival (OS) and event-free survival (EFS) were 62% (56-69% with 95% Confidence intervals (CIs)) and 56% (49-62%), respectively. Treatment-related mortality (TRM) was 7.8%. Among patients without Down syndrome (DS) or acute promyelocytic leukemia (APL), the presence of t(8;21) or inv(16) was a significant good prognostic factor both in the univariate and multivariate analyses. Children with DS (N = 10) and APL (N = 14) also showed a good survival exceeding 70% in 5 years.
These results suggest that repetitive use of HD-Ara-C was effective and safe for childhood AML. However, further optimization of AML therapy is required.
多种强化化疗方法已使儿童急性髓系白血病（AML）的生存率得到提高。我们在此报告东京儿童癌症研究组（TCCSG）连续两项试验的长期结果，该试验在缓解期采用了基于大剂量阿糖胞苷（HD-Ara-C）的联合化疗并重复使用。
1991年8月至1998年9月，共有216例新诊断为AML的符合条件儿童在TCCSG的两项连续多中心试验M91-13和M96-14中接受治疗。在M91-13试验中，患者在缓解诱导治疗后接受8个疗程的强化缓解后化疗，包括6个含HD-Ara-C的疗程。自体造血干细胞移植（HSCT）可由医生选择，如有可用供体则分配异体HSCT。在M96-14试验中，化疗组省略了最后两个HD-Ara-C疗程。
缓解诱导率为88.8%，5年总生存率（OS）和无事件生存率（EFS）分别为62%（95%置信区间（CI）为56-69%）和56%（49-62%）。治疗相关死亡率（TRM）为7.8%。在无唐氏综合征（DS）或急性早幼粒细胞白血病（APL）的患者中，t(8;21)或inv(16)的存在在单变量和多变量分析中均是显著的良好预后因素。DS患儿（n = 10）和APL患儿（n = 14）5年生存率也超过70%。
这些结果表明，重复使用HD-Ara-C对儿童AML有效且安全。然而，AML治疗仍需进一步优化。
