儿童急性髓系白血病早期治疗反应的预后价值

Prognostic value of early treatment response in children with acute myeloid leukemia

目的评价诱导治疗结束第48小时骨髓不同比例幼稚细胞数及诱导治疗第1疗程结束是否达完全缓解在儿童急性髓系白血病(AML)治疗中的预后价值。方法进入AML-XH-99方案的61例新诊治患儿,诱导治疗第1疗程结束后第48小时及诱导治疗第1疗程结束达完全缓解时行骨髓形态学检查。生存分析采用Kaplan-Meier方法;各组生存率的比较采用Log-rank检验;各生物学特征的比较采用x2检验或Fisher精确概率法(双尾);COX风险比例模型用于评估独立预后因素。结果诱导治疗结束后第48小时骨髓幼稚细胞≥0．15(n=11)与<0．15(n=35)的患儿5年无事件生存(EFS)率差异有统计学意义(18％±15％和49％±11％,P=0．0079);诱导治疗结束后第48小时骨髓不同比例幼稚细胞与患儿诱导治疗第1疗程是否达完全缓解明显相关(P=0．000 028 8)。诱导缓解治疗第1疗程结束达完全缓解时骨髓存在形态学可识别的幼稚细胞(0．00<幼稚细胞< 0．05)的患儿(n=36)5年EFS率为53％±10％,而此时无形态学可辨认的幼稚细胞(幼稚细胞= 0．00)的患儿(n=3)5年均长期存活。诱导缓解治疗第1疗程结束达完全缓解(n=39)与第1疗程结束未完全缓解的患儿(n=22)5年EFS率差异有统计学意义(54％±10％和10％±9％,P=0．0002);多因素分析显示诱导治疗第1疗程结束达完全缓解及起病时有中枢神经系统白血病具有独立的预后价值(风险比例分别为4．007,7．050;95％可信区间分别为1．019-6．613、0．018-0．547,P值分别为0．045,0．008]。结论诱导治疗第1疗程是否完全缓解具有独立的预后价值;诱导治疗结束第48小时骨髓幼稚细胞数可用于预测患儿是否能够诱导治疗1疗程达完全缓解,以便及时采取干预措施提高AML患儿的第1疗程完全缓解率及长期EFS率。

Objective To assess the prognostic value of early treatment response in children with acute myeloid leukemia （AML）. Methods Sixty-one children with AML, 37 male and 24 female, aged 96 months （6-154 months）, underwent treatment according to the protocol AML-XH-99 with a total treatment course of 15 months and were followed up for 12 months （1-74 months）. Bone marrow smear was made 48 hours after the end of the first course of induction treatment. Then the children were divided into 2 groups according to the number of bone marrow blast cells： group with the number of blast cells≥0. 15 and group with the number of blast cells 〈 0. 15. Second bone marrow smear was made when complete remission was achieved after the end of the treatment course. Then the children were divided into 2 groups according to the number of bone marrow blast cells： group with the number of blast cells of 0. 00 and group with the number of blast cells between 0. 00 and 0. 05. The probability of event-free survival （EFS） was estimated by KaplanMeier analysis. Log-rank test was used to compare the 5-year EFS （pEFS） of different groups. The differences in the biological features were compared by Chi-square analysis or Fisher exact test. Results The pEFS of the group with the number of blast cells≥0. 15 was 18% ± 15%, significantly shorter than that of the group with the number of blast cells 〈0. 15 （49% ± 11% ,P =0.079）. The 3 patients without morphologically identifiable blast all survived 5 years after complete remission had been achieved, and the pEFS of the 39 patients with the number of blast cells between 0. 00 and 0. 05 was 53% ± 10%. The pEFS of the patients among which complete remission was achieved after the first course of treatment （n =39） was 54% ± 10%, significantly higher than that of the patients without complete remission after the first course of treatment （10% ± 9%, P = 0. 0002 ） . Multiple factor analysis showed that achievement of complete remission after the first course of treatment and existence of central nervous system leukemia were both independent prognostic factors with the hazard ratios of 4. 007 and 7. 050 respectively and the 95% confidential intervals of 1. 019 to 6. 163 and 0. 018 to 0. 547 respectively （P =0. 045 and P =0. 008）. The number of blasts 48 hours after the end of the first course of induction treatment was highly correlated with the rate of complete remission after the first treatment course （ P = 0. 000 028 8 ）. Conclusion With important prognostic significance, early treatment response, such as the number of blasts 48 hours after the end of the first course of induction treatment can predict whether complete remission can be achieved.