Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children. Methods: The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model. Results: In the 68 cases, the proportion of male to female was 2.1∶1, with a median age of 8 (1-16) years, and the median overall survival (OS) and disease free survival (DFS) were 16.8 months and 13.5 months, respectively. The early response rate to treatment was 43.9%, with myeloid-antigens-expression group lower than the non-expression group (29.6% vs 61.3%, χ2=5.814, P=0.020); The complete remission (CR) rate after one-course induction therapy was 86.2% (56/65), with good-response group higher than the poor-response group (100.0% vs 74.2%, χ2=6.680, P=0.003);The CR rate after induction in patients receiving imatinib plus chemotherapy was higher than the patients receiving chemotherapy only (94.9% vs 73.1%, χ2=5.185, P=0.024). The 2-and 5-year OS were (61.4±7.0)% and (50.8±8.1)%, respectively. The 2-and 5-year DFS were (54.6±6.8)% and (48.6±7.3)%, respectively. Univariate analysis showed that the initial WBC, LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year OS rate (all P<0.05). LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year DFS rate (all P<0.05). Multivariate prognostic analysis for OS (RR=45.7, 95% CI 1.4-1 528.2, P=0.033) and DFS (RR=52.3, 95% CI 1.6-1 725.9, P=0.026) showed that the spleen ≥ 3 cm was the independent risk factor. Conclusions: Pediatric Ph+ ALL is a special condition with unique clinical and biological features. The early response to treatment was poor in patients with myeloid-antigens-expression, which resulted in a low CR rate after one-course induction and the administration of imatinib can remarkably improve the CR rate. Initial spleen ≥ 3 cm is an independent prognostic factor. The efficacy of chemotherapy alone is poor, and imatinib combined with chemotherapy is applauded in the aim of improving outcomes.
目的： 探讨儿童Ph染色体阳性和（或）BCR-ABL融合基因阳性急性淋巴细胞白血病（Ph+ ALL）的临床特征及预后影响因素。 方法： 回顾性分析北京大学人民医院儿科2006年12月至2016年12月收治的68例初治Ph+ ALL患儿的临床资料。采用Kaplan-Meier法进行生存分析，χ2检验及Log-rank检验评估各因素对预后的影响，多因素分析采用Cox回归模型。 结果： 68例Ph+ ALL患儿男女比为2.1∶1，中位年龄8（1~16）岁，中位总生存（OS）时间16.8个月，中位无病生存（DFS）时间13.5个月。早期治疗反应良好率为43.9%（29/66），伴髓系抗原表达组与不伴髓系抗原表达组的早期治疗反应良好率分别为29.6%和61.3%（χ2=5.814, P=0.020）。1个疗程完全缓解（CR）率为86.2%（56/65），早期治疗反应良好组与不良组的1个疗程CR率分别为100.0%和74.2%（χ2=6.680, P=0.003）。诱导化疗期加用伊马替尼组与单纯化疗组的1个疗程CR率分别为94.9%和73.1%（χ2=5.185, P=0.024）。2年和5年的OS率分别为（61.4±7.0）%和（50.8±8.1）%，2年和5年的DFS率分别为（54.6±6.8）%和（48.6±7.3）%。单因素分析显示，Ph+ ALL患儿的2年OS率与初诊WBC、LDH水平、脾脏大小、肝脏大小、是否伴髓系抗原表达、早期治疗反应、1个疗程后流式细胞术检测的MRD水平（或BCR-ABL）、是否应用伊马替尼及不同治疗方案等因素有关（P值均<0.05），2年DFS率与LDH水平、脾脏大小、肝脏大小、是否伴髓系抗原表达、早期治疗反应、1个疗程后流式细胞术检测的MRD水平（或BCR-ABL）、是否应用伊马替尼及不同治疗方案等因素有关（P值均<0.05）。多因素分析显示脾脏肋缘下≥3 cm是影响患者OS（RR=45.7, 95% CI 1.4~1 528.2, P=0.033）及DFS（RR=52.3, 95% CI 1.6~1 725.9, P=0.026）的独立预后危险因素。 结论： 儿童Ph+ ALL具有独特的临床和生物学特征。免疫分型中伴髓系抗原表达患儿的早期治疗反应差。早期治疗反应差的患儿1个疗程CR率低，诱导化疗期加用伊马替尼可明显提高1个疗程CR率。脾脏肋缘下≥3 cm是影响患者预后的独立危险因素。单纯化疗疗效差，化疗联合伊马替尼可以明显提高疗效。.
Keywords: Childhood; Imatinib; Leukemia, lymphoid, acute; Philadelphia chromosome; Prognosis.