两种方案治疗儿童急性早幼粒细胞白血病的总体预后对比分析

Comparison of the overall treatment outcome of two protocols for childhood acute promyelocytic leukemia

目的 对比先进国家的治疗方案和该院常规治疗方案对儿童急性早幼粒细胞白血病（APL）的疗效、预后及费用等,为改善中国APL患者的预后提供参考.方法 人组标准为15岁以下、FAB形态学符合APL和t（15;17）/PML-RARα阳性的患者.1999年11月至2004年9月共有16例符合入选条件,采用该院APL化疗方案治疗（包含诱导缓解后高强度的大剂量阿糖胞苷和米托蒽醌巩固治疗）.2004年9月至2008年1月有14例入选,采用低强度的改良西班牙PETHEMA LPA99方案治疗.结果 用该院方案治疗的16例均纳入统计,3.5年无事件生存（EFS）率37.5%（s^-x=0.121）,放弃治疗6例（37.5%）,死于诊断时颅内出血和治疗期间败血症各1例（6.3%）,复发2例（12.5%）.用改良PETHEMA方案治疗的14例患者3.5年EFS为79.6%（s^-x=0.136）,死于诊断时颅内出血1例（7.1%）,复发1例（7.1%）.两种方案对比,用改良PETHEMA方案治疗儿童APL在统计学上有较高的EFS（P=0.012）,较低的败血症发生率（7.7%：77.8%,P=0.0015）,较低的住院治疗费用（中位数3.52万元：15万元.P＜0.0001）及随之较低的放弃治疗率.结论 用改良 PETHEMA 方案治疗儿童APL有较低的治疗并发症和较低的住院治疗费用,复发率无增加,减少了治疗相关毒性和治疗放弃率,使整体预后明显改善.

Objective For further improving the prognosis of childhood acute promyelocytic leukemia （APL） in China,the treatment efficacies, outcomes and costs of protocols for childhood APL between in developed countries and in our hospital were compared. Methods 30 cases aged 〈15 years were diagnosed according to the FAB classification and detection of PML-RARα rearrangement. From December 1999 to September 2004,sixteen eligible children were treated with an intensive in-house protocol including high-dose Ara-C and anthracycline for post remission treatment. From September 2004 to January 2008,14 cases enrolled were treated with a less intensive protocol modified from the PETHEMA LPA99. Results The 3.5 years EFS was 37.5 % （s^-x=0.121） for total 16 patients on in-house protocol. Six patients （37.5 %） abandoned treatment,2 died of intracranial hemorrhage at diagnosis （6.3 %） and sepsis in remission （6.3 %）,respectively,and 2 relapsed （12.5 %）. The 14 cases treated with modified PETHEMA had a 3.5 years EFS of 79.6 % （s^-x=0.136）. One died of intracranial hemorrhage at diagnosis （7.1 %） and 1 relapsed （7.1 %）. Patients on modified PETHEMA had a significantly higher EFS （P=0.012）,lower frequency of sepsis during treatment （7.7 % vs 77.8 %; P=0.0015） and lower hospitalization cost （median,RMB 35 200 vs 150 000; P 〈0.0001） than those on in-house protocol. Conclusion Treatment with the less intensive protocol based on the PETHEMA LPA99 study for childhood APL successively reduced complication of chemotherapy and reduced hospitalization cost without increasing relapses, which led to decreases in treatment-related toxicity and treatment abandonment rate,thus improving overall outcome.