儿童急性髓系白血病的免疫学特征与预后的关系

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目的急性髓系白血病(AML)免疫表型与AML患者的化疗效果及预后的关系至今未达成共识。该文分析儿童AML免疫表型与FAB形态学分型以及染色体核型异常的关系,评价儿童AML免疫表型与治疗相关因素及预后的临床重要性。方法自1998年1月1日至2003年5月31日进入AML-XH-99治疗方案的所有在我院新诊治的AML患儿,诊断采用M ICM分型诊断,治疗按AML-XH-99危险度分类标准进行分层治疗。用流式细胞仪进行免疫表型分析,将免疫表型结果分为5组,髄系免疫标志CD13,CD33,MPO(自2001年9月采用单抗胞浆内标记);髓系相关抗原CD14,CD15;系性特异抗原-红系免疫标志G lyA,巨核系细胞标志CD41;淋系相关抗原CD19,CD7;非系列特异性抗原CD34,HLA-DR。分别计算各免疫表型在FAB形态学分型及染色体核型中表达的灵敏度及阳性预测值;各免疫表型的生存分析采用Kap lan-M e ier方法;生存之间的比较采用log-rank检验;各免疫表型患儿一疗程缓解率的比较采用2χ检验或F isher精确概率法(双尾);COX比例风险模型用于分析单独各免疫表型进入回归方程中是否为独立预后因素。结果①74例患儿中有72例(97.3%)患儿至少有CD13、CD33、MPO中的一种或两种抗原阳性表达;45例(60.8%)患儿有两个或两个以上髓系抗原表达,伴有淋系相关抗原表达的为18例,占24.3%。在M2患儿中,常伴有淋系抗原CD19的表达,阳性预测值(PPV)为75%;FAB分型为急性早幼粒细胞白血病的患儿,缺乏HLA-DR及淋系相关抗原(CD19或CD7)的表达,阴性预测值(NPV)为100%;CD41阳性表达与M7相关,PPV为66.7%;②单因素分析显示各免疫表型与AML患儿的一疗程缓解率及长期无事件生存(EFS)率无关;③多因素分析显示各免疫表型均无独立的预后价值。结论儿童AML患儿的免疫表型对预后无明显影响,不能单独用于治疗前危险度的评估,但可帮助识别某些特殊类型的AML患儿。 Objective Acute myeloid leukemia (AML) immunophenotype and the relationship between the chemotherapy effect and prognosis of AML patients have not reached a consensus. This article analyzes the relationship between childhood AML immunophenotype and FAB morphological typing and chromosomal abnormalities, and evaluates the clinical significance of immunophenotype and treatment related factors and prognosis in children. Methods From January 1, 1998 to May 31, 2003, all AML children newly diagnosed with AML-XH-99 in our hospital were diagnosed by M ICM classification and treated according to AML-XH-99 Risk classification criteria for stratified treatment. The immunophenotypes were analyzed by flow cytometry and the immunophenotype results were divided into five groups: immunofluorescent markers CD13, CD33, and MPO (cytoplasmic markers were labeled with McAb in September 2001); myeloid-associated antigen CD14 , CD15; Department of specific antigen - erythroid immune markers G lyA, megakaryocyte markers CD41; lymph node-associated antigens CD19, CD7; non-series specific antigen CD34, HLA-DR. The sensitivity and positive predictive value of each immunophenotype in FAB morphological type and karyotype were calculated respectively. Survival analysis of each immunophenotype was performed by Kaplan-Meier method. The comparison of survival was performed by log-rank test . The response rate of each immunophenotype in children was compared by 2χ test or Fisher’s exact test (two-tailed). The COX proportional hazard model was used to analyze whether individual immunophenotypes entered the regression equation as independent prognostic factors. Results ① Of the 74 children, 72 (97.3%) had at least one of CD13, CD33 and MPO positive expression, and 45 (60.8%) had two or more myeloid Antigen expression, associated with lymphoid-associated antigen expression was 18 cases, accounting for 24.3%. In children with M2, the expression of CD19 was often associated with a 75% positive predictive value (PPV). Children with FAB genotype acute promyelocytic leukemia lacked HLA-DR and lymphoid-associated antigens ( CD19 or CD7). The negative predictive value (NPV) was 100%. The positive expression of CD41 was associated with M7 and the PPV was 66.7%. (2) The univariate analysis showed that the response rate and long-term Event-free survival (EFS) rate unrelated; multivariate analysis showed no independent prognostic value of each immune phenotype. Conclusion The immunophenotype in children with AML has no significant effect on the prognosis and can not be used alone for the assessment of pre-treatment risk, but may help identify some specific types of children with AML.
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