儿童急性髓系白血病的免疫学特征与预后的关系

Relationship between immunological characteristics and prognosis in children with acute myeloid leukemia

摘要:

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MICM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GlyA，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Kaplan-Meier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χ2检验或Fisher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：① 74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。［中国当代儿科杂志，2009，11（4）：241-245］

Abstract:

OBJECTIVE: The prognostic significance of immunophenotyping in acute myeloid leukemia (AML) has been controversial. This study investigated the relationship of immunophenotypes with French-American-British (FAB) subtypes and chromosomal abnormalities and assessed the prognostic value of immunophenotyping in children with AML. METHODS: From January 1998 to May 2003, 75 children with newly diagnosed AML were enrolled on protocol AML-XH-99. Immunophenotypes were measured with the flow cytometry. According to the McAbs used, the patients were classified into five groups: panmyeloid antigens (CD13, CD33, and MPO), myeloid-lineage associated antigens (CD14, CD15), lineage-specific antigens (CD41, GlyA), progenitor-associated antigens (CD34, HLA-DR) and lymphoid-associated antigens (CD19, CD7). The probability of event-free survival (EFS) was estimated by Kaplan-Meier analysis. The distributions of EFS were compared using the log-rank test. Chi-square analysis or Fisher exact test was used to compare the differences in the distribution of biologic presenting features. A Cox proportional hazards model was used to identify independent prognostic factors. RESULTS: At least one of panmyeloid antigens CD13, CD33 and MPO was expressed in 72 patents (97.3%). Two or more panmyeloid antigens were expressed in 45 patients (60.8%). The proportion of children with AML expressing one or more of the lymphoid-associated antigens was 24.3%. Lymphoid-associated antigen CD19 was expressed by blast cells in most of FAB M2 patients. The patients with acute promyelocytic leukemia were characterized by the absence of HLA-DR and lymphoid-associated antigens CD19 and CD7. Monovariate analysis showed immunophenotypes were not related to the complete remission rate after the first induction course and the 5-year-EFS. Multivariate analysis suggested immunophenotyping had no independent prognostic value in AML.CONCLUSIONS: Immunophenotyping can not be used independently in the evaluation of risk classification in children with AML. However, it is useful in the reorganization of special types of AML.［Chin J Contemp Pediatr, 2009, 11 (4):241-245］