儿童急性淋巴细胞白血病早期治疗反应的预后价值：上海儿童医学中心单中心的临床报告

Prognostic value of early treatment response in childrenwith acute lymphoblastic leukemia: a single institution experience in Shanghai, China

摘要:

目的：在儿童急性淋巴细胞白血病（ALL）治疗中，早期治疗反应是最重要的预后因素之一。该文评价了诱导治疗第19天及血液学完全缓解时骨髓存在形态学可辨认的幼稚淋巴细胞数及微量残留病(MRD)监测在儿童ALL治疗中的预后价值。方法：1998年1月至2003年5月接受ALL-XH-99方案治疗的193例新诊治的ALL患儿为研究对象。联合化疗第19天及诱导缓解治疗结束时行骨髓形态学检查以及血液学缓解时用四色MP-FCM检测MRD。生存分析采用Kaplan-Meier方法，各组无事生存率（EFS）之间的比较采用log-rank检验，各生物学特征的比较采用χ2检验或Fisher确切概率法（双尾），COX风险比例模型用于评估预后因素。结果：①诱导治疗第19天骨髓幼稚淋巴细胞≥5%与<5%的患儿4年EFS差异有非常显著性意义 (42.59%±14.28% vs 74.24%±6.67%；P<0.01)；②诱导缓解治疗结束达血液学缓解时存在形态学可识别的幼稚淋巴细胞（幼稚淋巴细胞>0%）与此时无形态学可辨认的幼稚淋巴细胞的患儿4年EFS差异有显著性意义（63.47%±9.23% vs 76.41%±6.09%; P<0.05）；③ 诱导缓解治疗结束血液学完全缓解时 MRD≥0.01%与 MRD<0.01%的患儿15月EFS差异有非常显著性意义（23.81%±20.26% vs 94.44%±5.40%; P<0.01）。结论：诱导治疗第19天骨髓幼稚细胞数≥5%、诱导治疗结束血液学缓解时骨髓幼稚细胞＞0%及MRD监测在儿童急性淋巴细胞白血病治疗中具有预后价值，可用于发展中国家儿童ALL早期治疗反应的评估。［中国当代儿科杂志，2009，11（1）：5-9］

Abstract:

OBJECTOVE: Early response to therapy is one of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL). This study aimed to assess the prognostic value of morphological assessment of bone marrow blasts during remission induction and determination of minimal residual disease (MRD) after remission induction. METHODS: From January 1998 to May 2003, 193 children with newly diagnosed ALL were enrolled on the ALL-XH-99 protocol. Blast cell count in the bone marrow was examined on day 19 of remission induction and by the completion of remission induction. MRD was measured with the flow cytometry. Event-free survival (EFS) was estimated by Kaplan-Meier analysis and the distributions of EFS were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. RESULTS: The 4-year EFS was significantly worse in patients with ≥ 5% lymphoblasts in the bone marrow on day 19 as compared to those with <5% lymphoblasts on that date (42.59%±14.28% vs 74.24%±6.67%; P<0.01). The 4-year EFS was significantly worse in patients with any amount of lymphoblasts in the bone marrow on the remission date as compared to that of other patients with no morphologically identifiable blasts (63.47%±9.23% vs 76.41%±6.09%; P<0.05). The patients with MRD <0.01 had significantly better outcome than those with a level ≥ 0.01% (15-month EFS:94.44%±5.40% vs 23.81%±20.26%; P<0.01). CONCLUSIONS: Early treatment response as assessed by morphological examination or minimal residual leukemia determination by flow cytometry has important prognostic significance, and can be performed in a resource-poor patient population.［Chin J Contemp Pediatr, 2008, 11 (1):5-9］