Correlation between circulating lymphocyte ratio and early death of acute promyelocytic leukemia
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摘要: 目的 探索循环淋巴细胞比例(LYR)在初发急性早幼粒细胞白血病(APL)早期死亡中的意义。方法 收集2017年1月—2022年1月在血液科初诊、初治的APL患者111例，收集这些患者治疗前的临床数据，包括性别、年龄、血红蛋白(Hb)、白细胞计数(WBC)、血小板计数(PLT)、LYR、循环单核细胞比例(MOR)、骨髓及外周血早幼粒细胞比率、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、D-二聚体(D-D)。根据是否发生早期死亡分为早期死亡组和非早期死亡组，分析早期死亡的相关因素，对单因素有意义的指标行受试者工作特征(ROC)曲线分析，以LYR及MOR的截断值为界，分为高LYR组和低LYR组；高MOR组和低MOR组。纳入单因素有意义的指标行多因素分析明确早期死亡的独立危险因素。结果 111例初发APL患者中18例发生早期死亡，简单关联性分析中与无早期死亡组比较，早期死亡组外周血早幼粒细胞比率、骨髓早幼粒细胞比率、WBC、MOR较高，LYR较低，PT延长。ROC分析显示预测效能较好的指标有PT、LYR、MOR的AUC分别为0.751、0.736、0.704。多因素分析结果示LYR≤17.8%为APL患者早期死亡的独立危险因素(OR＝0.182，95%CI 0.037~0.898，P＝0.036)。进一步分析结果显示低LYR组(LYR≤17.8%)以男性较多，外周血早幼粒细胞比率、骨髓早幼粒细胞比率、WBC、Hb、FIB、MOR较高，PT延长。结论 初诊时低LYR是初发APL早期死亡重要的预测因子，尤其当其数值≤17.8%时早期死亡风险增加，需格外注意。
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关键词:
- 急性早幼粒细胞白血病 /
- 早期死亡 /
- 循环淋巴细胞比例
Abstract: Objective To explore the significance of circulating lymphocyte ratio(LYR) in early death of primary acute promyelocytic leukemia(APL).Methods A total of 111 newly diagnosed and newly treated APL patients in the Department of Hematology from January 2017 to January 2022 were collected. The clinical data of these patients before treatment were collected, including gender, age, hemoglobin(Hb), white blood cell(WBC), platelet(PLT), LYR, circulating monocyte ratio(MOR), bone marrow and circulating leukemic promyelocyte ratio, prothrombin time(PT), activated partial thromboplastin time(APTT), fibrinogen(FIB), D-dimer(D-D). They were divided into early death group and non-early death group according to the occurrence of early death. The related factors of early death were analyzed. The receiver operating characteristic(ROC) curve analysis was performed on the meaningful indicators of univariate analyses. According to the cut-off value, the proportion of circulating lymphocytes and the proportion of circulating monocytes were divided into high LYR group and low LYR group, high MOR group and low MOR group, respectively. Multivariate analysis was performed using the indicators with statistically significant results based on the univariate analysis to identify independent risk factors for early death.Results A total of 18 of 111 patients with primary APL had early death. In univariate analysis, compared with non-early death group, early death group had higher peripheral circulating promyelocyte ratio, bone marrow promyelocyte ratio, WBC and MOR, lower LYR and longer PT. ROC analysis showed that the AUC of PT, LYR and MOR were 0.751, 0.736 and 0.704, respectively. Multivariate analysis showed that LYR≤17.8 % was an independent risk factor for early death in APL patients(OR=0.182, 95 % CI 0.037-0.898, P=0.036). Further analysis showed that the low LYR group(LYR≤17.8 %) had more males, higher promyelocyte ratio, bone marrow promyelocyte ratio, WBC, Hb, FIB, MOR, and prolonged PT.Conclusion Low LYR at initial diagnosis may be an important predictor of early death in newly diagnosed APL, especially when its value ≤17.8%, the risk of early death increases, and special attention should be paid.-
Key words:
- acute promyelocytic leukemia /
- early death /
- circulating lymphocyte ratio
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表 1 影响APL患者早期死亡的单因素分析
影响因素 无早期死亡组(n=93) 早期死亡组(n=18) P 性别/例 0.209 男 47 12 女 46 6 年龄/岁 44.77±14.63 45.17±36.00 0.920 外周血早幼粒细胞比率/% 39.21(60.00) 56.64(64.50) 0.033 骨髓早幼粒细胞比率/% 74.03(20.00) 83.33(16.30) 0.029 WBC/(×109·L-1) 10.45(7.33) 28.23(47.37) 0.013 Hb/(g·L-1) 78.61±22.07 83.63±23.94 0.375 LYR/% 43.83(46.64) 23.41(34.39) 0.002 MOR/% 23.61(28.78) 36.23(31.40) 0.006 PLT/(×109·L-1) 35.54(28.18) 20.39(11.69) 0.592 PT/s 13.97(2.50) 15.27(2.6) 0.005 APTT/s 27.16(4.55) 30.59(8.28) 0.243 FIB/(g·L-1) 1.63(1.09) 3.80(1.83) 0.813 D-D/(mg·L-1) 20.08(16.30) 20.52(18.68) 0.381 
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表 2 预测指标对于APL患者早期死亡事件的诊断效能分析
指标 AUC(95%CI) 截断值 灵敏度/% 特异度/% P 外周血早幼粒细胞比率 0.659(0.563~0.746) 79.00 44.4 84.9 0.028 骨髓早幼粒细胞比率 0.663(0.567~0.750) 75.00 83.3 45.2 0.022 WBC 0.686(0.591~0.771) 16.33 55.6 81.7 0.011 PT 0.751(0.667~0.823) 14.70 71.4 73.8 < 0.001 LYR 0.736(0.664~0.815) 17.80 61.1 81.7 < 0.001 MOR 0.704(0.610~0.787) 18.37 88.9 50.5 < 0.001
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表 3 APL患者早期死亡的多因素分析
变量 P OR 95%CI WBC 0.430 1.010 0.985~1.037 PT 0.338 1.175 0.854~1.633 外周血早幼粒细胞比率 0.100 0.974 0.944~1.005 骨髓早幼粒细胞比率 0.100 0.974 0.988~1.121 LYR HL 0.036 0.182 0.037~0.898 LL MOR HM 0.121 3.921 0.696~22.096 LM
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表 4 LL组和HL组临床资料比较
变量 HL(n=83) LL(n=28) P 性别/例 0.025 男 39 20 女 44 8 年龄/岁 45.95±15.18 41.54±14.87 0.184 外周血早幼粒细胞比率/% 31.52(48.00) 73.20(25.00) < 0.001 骨髓早幼粒细胞比率/% 72.92(20.50) 83.30(14.60) 0.002 WBC/(×109·L-1) 5.44(3.44) 36.74(42.78) < 0.001 Hb/(g·L-1) 75.99±20.12 89.60±23.92 0.004 LYR/% 51.39(37.10) 8.30(6.51) < 0.001 MOR/% 19.81(27.00) 24.81(30.09) < 0.001 PLT/(×109·L-1) 33.64(34.00) 23.75(16.74) 0.312 PT/s 13.74(2.80) 15.49(2.80) < 0.001 APTT/s 27.49(5.00) 28.37(5.70) 0.770 D-D/(mg·L-1) 1.75(1.12) 2.67(1.16) 0.029 FIB/(g·L-1) 21.99(20.42) 14.67(11.62) 0.104
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