儿童ALL治疗中骨髓细胞形态学动态监测及其意义

DYNAMIC MONITORING BONE MARROW CELL MORPHOLOGY AND ITS SIGNIFICANCE IN THE THERAPY OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

目的了解骨髓细胞形态学动态监测在儿童急性淋巴细胞白血病(ALL)治疗预后中的价值。方法采用回顾性研究方法,对我院2006年8月—2010年3月收治并获得系统治疗的70例ALL病儿进行Kaplan-Meier分析,监测完全缓解治疗第19、33天以及初次缓解后维持治疗过程中,骨髓原始+幼稚淋巴细胞比例,并采用COX比例风险回归模型对各影响因素进行分析。结果诱导完全缓解治疗第19天原始+幼稚淋巴细胞比例<5%组生存率高于5%～25%组,差异有统计学意义(χ2=25.320,P<0.001);第33天完全缓解组生存率显著高于部分缓解组(χ2=21.676,P<0.001)。维持治疗中原始+幼稚淋巴细胞比例5%组生存率高于5%～20%组(χ2=14.347,P<0.001);原始+幼稚淋巴细胞比例5%～20%病人按出现的时间距初次获得完全缓解时间分为3组,其中0.5～1.0年组与0.5年内组生存率差异无统计学意义(χ2=2.951,P>0.05),1.0年后组生存率显著高于1.0年内组(χ2=16.416,P<0.001);1年内出现频率≤3次组生存率高于>3次组(χ2=15.075,P<0.001)。原始+幼稚淋巴细胞比例5%～20%的标危、中危及高危病儿生存率依次降低(χ2=23.099,P<0.001),B细胞系ALL生存率高于T细胞系ALL(χ2=8.476,P<0.05)。多因素分析结果显示,1年内骨髓原始+幼稚淋巴细胞比例5%～20%出现频率>3次(RR8.180,95%CI 2.371～28.217,P=0.001)、高危型(RR3.013,95%CI 1.146～7.918,P=0.025)、T细胞系(RR7.064,95%CI 1.968～25.359,P=0.003)为预后影响因素。结论动态监测骨髓细胞形态学原始+幼稚淋巴细胞比例在ALL个体化施治中有极大临床指导意义。

Objective To study the value of dynamic monitoring of bone marrow cell morphology in predicting the prog- nosis of childhood acute lymphoblastic leukemia （ALL）. Methods A retrospective review was done for 70 children with ALL treated in our hospital during 2006.08--2010.03, and Kaplan-Meier analysis carried out. The proportion of marrow blasts -- juve- nile lymphocytes （MB--JL） was monitored on days 19 and 33 after complete remission （CR） and in the process of maintenance therapy after primary remission （PR）. Various influencing factors were analyzed by employing COX proportional hazards regression model. Results The survival rate in M1 group was higher than M2 group （x2 =25.320,P〈0.001）, that of CR was higher than PR on the 33th day （x2 =21.676, P〈0.001）. During maintenance chemotherapy, the survival rate in MB＋JL〈5% group was higher than MB＋JL= 5%--20% group （x2=14. 347,P〈0.001）. The patients with 5%--20% of MB--JL were divided into three groups based on the time from the CR. The survival rate was not significant between 0.5--1.0-year and 〈0.5-year group （x2 2.951,P〉0.05）, that in the 〉1.0-year group was higher than 〈1.0 year group （x2 =16.416,P〈0.001）, that the frequency of MB＋JL （5%-20%） appeared 43 times within one year was higher than that of 〉3 times （x2= 15.075,P〈0.001）. The survival rate of standard risk, moderate risk, and high risk patients with 5%-20% MB＋JL was decreased in this order （%2 =23.099,P〈 0.001）, that of B cell line was higher than T cell line （x2 = 8.476, P 〈0.05）. Multivariate analysis indicated that the prognostic in- fluencing factors including high frequency （〉 3） within one year after chemotherapy （RR 8. 180 ： 95 % CI 2.371 -- 28.217, P = 0.001）, high-risk type patients （RR 3.013; 95%CI 1.146--7.918,P=0.025） and T-ALL patients （RR 7.064; 95%CI 1.968-- 25.359,P=0.003）. Conclusion Dynamic monitor of MB＋JL ratio is of great clinical guiding significance in the individualized therapy for ALL.