初治急性白血病P-糖蛋白及其预后的前瞻性队列研究

A prospective cohort study on multidrug resistance associated P glycoprotein as a prognostic factor of complete remission in acute leukemia at diagnosis

目的了解多药耐药相关Ｐ糖蛋白（Ｐｇｐ）是否为初治急性白血病（ＡＬ）完全缓解（ＣＲ）的预后因素。方法对４８例年龄为１５～７０岁未经化疗的初发ＡＬ患者进行前瞻性、截矩性队列研究。ＡＬ诊断和ＣＲ标准按照美、英、法（ＦＡＢ）小组标准。Ｐｇｐ用单克隆抗体ＵＩＣ２标记后经流式细胞仪检测。暴露组和非暴露组分别为Ｐｇｐ阳性和阴性ＡＬ患者。结果变量：经两疗程标准化疗取得ＣＲ的病例数和未缓解病例数。用单因素和多因素逻辑回归分析。结果Ｐｇｐ阴性和阳性组病例数为２５和２３。两组ＣＲ率分别为６８％和２２％。经单因素分析，Ｐｇｐ阴性组较阳性组易取得ＣＲ（ＲＲ＝７．６５，９５％ＣＩ２．１～２８，Ｐ＝０．００２）。年龄、性别、发病时白细胞数、骨髓原＋（早）幼细胞比例和ＦＡＢ分型对ＣＲ无意义。经上述变量校正的多因素分析结果Ｐｇｐ仍对ＣＲ有显著意义（ＲＲ＝９．３，９５％ＣＩ２．２～３９，Ｐ＝０．００２）。Ｐｐｇ对诊断原发耐药白血病的敏感性６９％，特异性７７％，阳性预测值７８％，阴性预测值６８％，阳性似然比３，阴性似然比０．４，患病率５４％，准确性７３％。结论Ｐｇｐ阳性是初治急性白血病完全缓解的不利预后因素。

Objective To determine whether multidrug resistance associated P glycoprotein (Pgp) is a prognostic factor for complete remission (CR) in acute leukemia (AL) patients at diagnosis. Methods Prospective,inception,cohort study of 48 new AL cases with age from 15 to 70 years old without history of chemotherapy.Diagnosis and CR criteria of AL were according to the French American British (FAB) group criteria.The Pgp were tested by flow cytometric analysis using monoclonal antibody UIC2.Exposed and unexposed groups were Pgp positive and negative AL cases.Logistic regression was used to analyze between the CR rate the Pgp. Results The numbers of Pgp negative( ) and positive (+) cases were 25 and 23.The CR rate in the two groups were 68% and 22%,respectively.After the univariate analysis, Pgp (group was easier to get CR than Pgp+group (RR=7.65,95%CI2.1～28, P =0.002).Age,sex,initial white blood cell count (WBC),bone marrow (BM) blast percentage and FAB subtypes were not significant to the CR rate.Multivariate analysis adjusted by above factors shows that the Pgp was also highly significant to the CR rate (RR=9.3,95%CI 2.2～39, P =0.002).The sensitivity was 69%,specificity 77%,positive predictive value 78%,negative predictive value 68%,positive likelihood ratio 3,negative likelihood ratio 0.4,prevalence 54%,accuracy 73% for Pgp diagnosing the primary resistant AL cases. Conclusion Pgp+is an unfavorable prognositc factor for complete remission in acute leukemia patients at diagnosis.We could use it to predict the primary resistant acute leukemia case.