急性淋巴细胞白血病病儿微小残留病动态监测及意义

目的探讨动态监测微小残留病（MRD）在儿童急性淋巴细胞白血病（ALL）治疗中预后评估的价值。方法ALL病儿75例，在诱导缓解治疗第19、33天及维持治疗过程中通过流式细胞术监测MRD水平，根据MRD水平分为A组（MRD≤10 -4）、B组（MRD介于A组与C组间）、C组（MRD≥10 -2），根据Kaplan-Meier及COX比例风险回归模型进行分析。结果诱导缓解治疗第19天，A组的生存率明显高于B、C组（X2=6．435、19．795，P〈0．05）；诱导缓解治疗第33天，C组病儿的生存率显著低于其他两组（X2=5．057、8．346，P〈0．05）。维持治疗3个月、6个月、12个月、2年时MRD不同水平比较，差异有显著性（X2=6．133～22．558，P〈0．05）；治疗3年时MRD水平对生存率无影响（P〉0．05）。根据维持治疗过程中MRD≥10 -2出现在不同时间点分3组：半年内出现（I组）、半年到1年出现（Ⅱ组）、1年后出现（Ⅲ组），Ⅲ组的生存率高于I、Ⅱ组（X2=6．226、7．018，P〈0．05）。1年内出现MRD≥10 -2的病儿中高危型、T细胞系、融合基因阳性的生存率显著降低（X2=5．661～10．682，P〈0．05）。多因素分析显示，诱导缓解治疗第19天MRD水平是影响病儿预后的独立危险因素（RR=4．01；95％CI=0．968～8．995，P〈0．05）。1年内出现MRD≥10 -2 的病儿，高危型（RR 4．73；95％CI—1．316～14．624，P〈0．05）、T细胞型（RR1．78；95％CI=0．101～6．014，P〈0．05）、融合基因阳性（RR0．08；95％CI=0．008～0．801，P〈0．05）是影响预后的危险因素。结论动态监测MRD对ALL病儿预后有极大临床指导意义，有助于实施个体化治疗。

DYNAMIC MONITORING OF MINIMAL RESIDUAL DISEASE IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA AND ITS SIGNIFICANCE

Objective To assess the value of dynamic monitoring of minimal residual disease （MRD） in predicting the prognosis of childhood acute lymphohlastie leukemia （ALL）. Methods Seventy-five ALL patients were detected for MRD by flow cytometry on days 19 and 33 after remission induction chemotherapy and in maintenance therapy. They were divided into three groups as： group A （MRD≤10 -4）, group B （MRD between groups A and C）, and group C （MRD≥10 -2）. An analysis was con- ducted according to Kaplan Meier analysis and COX proportional hazards regression model. Results On day 19 of induction chemotherapy, the survival rate in group A was obviously higher than groups B and C （X2=6.435,19.795;P〈0.05） ; on day 33, the survival rate in group C was lower than the other two groups （X2=5.057,8.346 ;P〈0.05）. In maintenance chemotherapy peri od of 3 months, 6 months and 24 months, the differences of MRD levels between them were significant （X2= 6.133--22.558,P 〈0.05）. After three years of therapy, the MRD did not affect the survival （P〉0.05）. According to MRD≥10 -2 appeared at differ ent time points during treatment, the patients were divided into three groups as group 1, appeared within 6 months; group 2, ap- peared 6-12 months; group 3, appeared after 12 months. The survival in group 3 was higher than groups 1 and 2 （Z2 --6.226, 7.018;P〈0.05）. The patients with MRD≥10-2 appearing within the first year after induction chemotherapy, the survival rate in high-risk, T cell line, gene positive patients declined significantly （X2=5.661-10.682,P〈0.05）. Multivariate analysis suggested that the level of MRD on day 19 was an independent risk factor affecting patient＇s prognosis （RR 4.01;95 % CI = 0. 968--8. 995, P〈0.05）. The high-risk factors that affected the prognosis were MRD≥10 2 appeared within the first year after induction ehemo therapy, high-risk type （RR 4.73;95; CI=1.316--14.624,P〈0.06）, Tcellline （RR 1.78;95% CI=0.101 6.014,P〈0.05） and fused ge