ALL-2005方案治疗158例儿童急性淋巴细胞白血病诱导缓解期疗效评价及中期随访报告

Report on induction efficacy of protocol ALL-2005 and middle term follow-up of 158 cases of childhood acute lymphoblastic leukemia

目的在保证有效治疗的同时，降低儿童急性淋巴细胞白血病（ALL）诱导缓解期治疗风险。初步评价ALL-2005方案的临床疗效。方法ALL-2005方案是在ALL—XH-99方案的基础上作出修改，结合患儿诱导治疗第35、55天骨髓微量残留病（MRD）检测结果，按低危、中危和高危分组，分别予以不同强度的化疗。统计2005年5月1日至2007年4月31日初发ALL患儿158例，分析其诱导缓解率、诱导治疗相关并发症、诱导治疗第35天、55天MRD水平及随访结果。结果根据分组标准，158例患儿中低危组59例，中危组93例，高危组6例。35d诱导缓解率为98．1％。139例（88．0％）患者可找到MRD检测标志，诱导治疗第35天时137例患儿中94例MRD≤0．01％，占68．6％。43例（27．2％）患儿诱导期出现发热等感染征象；合并重症感染进入ICU2例（1．3％）。诱导期因合并症死亡1例（0．6％）。4例在治疗缓解状态下失访，失访率2．5％。全组复发17例，占10．8％，低危组4例，中危组11例，高危组2例。诱导治疗第35天MRD≤0．01％组复发者占4．3％（94例中4例），MRD〉0．01％组复发者占23．3％（43例中10例），两组间差异有统计学意义（P=0．003）。至2008年3月31日，中位随访时间为20（12—35）个月。预计30个月总体无病生存率为（81．6±4．5）％，低危组为（94．1±3．3）％，中危组为（82．8±4．4）％；诱导治疗第35天MRD≤0．01％组无病生存率为（91．0±5．4）％，〉0．01％组为（67．1±9．5）％；第55天MRD≤0．01％组为（89．1±5．3）％，〉0．01％组为（46．9±15．6）％。结论ALL-2005方案诱导治疗期患儿的感染率和治疗相关死亡率低，诱导缓解率和无病生存率均较高。诱导治疗第35天和第55天MRD水平对患儿预后有影响。

Objective To reduce the risk of infection during the induction therapy while to ensure remission rates, and to evaluate the protocol ALL-2005. Methods The minimal residual disease （MRD） was detected by flow cytometry on day 35 and 55 of induction therapy. The efficacy of induction and the clinic grouping were evaluated by MRD level. From May 1, 2005 to April 30, 2007, 158 children with newly diagnosed ALL were enrolled in this study. According to clinic grouping criteria of ALL-2005, patients were stratified into 3 groups ： low-risk （LR） , intermediate-risk （MR） and high-risk （HR）. The remission rates, therapy related complication during induction, and the relationship between MRD level on day 35 and 55 of induction and prognosis were analyzed. The endpoints are disease-free survival （DFS） , relapse and death of any cause. Patients lost to follow-up were censored at the time of their withdrawal. Results Of the 158 patients, 59 were LR, 93 MR and 6 HR. The CR rate on day 35 was 98. 1%. There were detectable MRD in 139 （88.0%） patients. In 94 patients （68.6%） MRDs were ≤0.01% on day 35 being 73.1% （49/67） for LR and 63.4% （45/71）for MR （P =0. 219）. During induction therapy, 43 patients （27.2%） developed infection and among them 1.3% （2/158） suffered serious infection and 0.6 % （1/158） died of complication. Four patients （ 2.5% ） in CR were lost follow-up, 17 patients （ 10.8% ） relapsed, including 4 patients（4.3%） with MRD≤0.01% and 10 （23.3%） 〉0.01% on day 35 （P =0.003）. One died of severe malnutrition and infection in CR. With a median follow-up of 20 （12 -35 ） months, the estimated 30 month DFS for whole group was （ 81.6 ± 4.5 ） % including （ 94.1 ± 3.3 ） % for LR, （ 82.8 ± 4.4 ） % for MR, and （91.0 ±5.4）% forMRD≤0.01%, （67.1 ±9.5）% forMRD〉0.01% on day 35 and （89.1±5.3）% for MRD ≤0.01% and （46.9±15.6）% forMRD 〉0.01% onday55. Conclusion The risk of infection and therapy related death during induction with protocol ALL-2005 are lower, while the remission rate and quality of the induction are better. Longer follow-up is needed to estimate the long-term result.