Abnormal Clinical Features and Prognosis of ACTH in Pediatric Acute B Lymphocytic Leukemia
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摘要:
目的 探讨促肾上腺皮质激素(ACTH)异常儿童急性B淋巴细胞白血病的临床特征及预后情况。 方法 收集2019年1月至2023年1月昆明市儿童医院血液科收治的54例B-ALL患儿为研究对象,根据是否存在ACTH降低分为降低组75例,正常组79例,收集患者临床资料进行比较,分析影响预后的危险因素。 结果 2组基线资料(性别,民族,年龄)、化疗次数、病情严重程度、血红蛋白、血小板计数、原始细胞百分比、复发率、死亡率、无事件生存率、总生存率、单因素、多因素COX回归分析临床因素对OS率的影响差异均无统计学意义(P > 0.05),外周血白细胞计数及分组、糖皮质激素(GC)抵抗率、MRD阳性率以及单因素Cox回归分析中年龄≥10岁、伴有中枢神经系统白血病、白细胞计数、白细胞分组( < 50×109/L vs ≥50×109/L)对初诊B-ALL患儿EFS率的影响差异有统计学意义(P < 0.05),睾丸浸润、血小板计数、血红蛋白水平、骨髓原始细胞计数、皮质醇水平、ACTH水平、性别、MRD、民族、分组(ACTH正常组VS ACTH降低组)、病情严重程度对初诊B-ALL患儿EFS率的影响差异无统计学意义(P > 0.05)。进一步行多因素Cox逐步回归分析(方法:向前,有条件)发现白细胞计数≥50×109/L、年龄≥10岁是患儿EFS率的独立不良预后因素(P < 0.05)。 结论 ACTH降低的B-ALL患儿GC抵抗率、MRD阳性率、白细胞计数更高,白细胞计数≥50×109/L、年龄≥10岁是患儿EFS率的独立不良预后因素。 Abstract:Objective To explore the clinical characteristics and prognosis of acute B lymphocytic leukemia in children with abnormal adrenal corticotropic hormone (ACTH). Methods A total of 154 children with B-ALL admitted to the hematology Department of Kunming Children’ s Hospital from January 2019 to January 2023 were collected as the study objects. According to whether ACTH decreased, they were divided into the reduced group (75 cases) and the normal group (79 cases). Clinical data of the patients were collected for comparison, and the risk factors affecting the prognosis were analyzed. Results The baseline data from two groups (gender, ethnicity, age), number of chemotherapy sessions, severity of illness, hemoglobin levels, platelet counts, percentage of blast cells, relapse rates, mortality rates, event-free survival rates, overall survival rates, and both univariate and multivariate COX regression analyses of clinical factors affecting OS rates showed no statistical significance (P > 0.05). However, peripheral blood leukocyte counts and groupings, glucocorticoid (GC) resistance rates, MRD positivity rates, and in the univariate Cox regression analysis, age ≥10 years, presence of central nervous system leukemia, leukocyte counts, and leukocyte groupings (50×109/L vs ≥50×109/L) had a statistically significant impact on the EFS rates of newly diagnosed B-ALL patients (P < 0.05). Testicular infiltration, platelet counts, hemoglobin levels, bone marrow blast cell counts, cortisol levels, ACTH levels, gender, MRD, ethnicity, groupings (normal ACTH group vs reduced ACTH group), and severity of illness on the EFS rates of newly diagnosed B-ALL patients was not statistically significant (P > 0.05). Further multivariate Cox stepwise regression analysis (method: forward, conditional) revealed that leukocyte counts ≥50×109/L and age ≥10 years are independent adverse prognostic factors for the EFS rates in these patients (P < 0.05). Conclusion Children with B-ALL with reduced ACTH had higher rates of GC resistance, MRD positivity, and white blood cell count, ≥50×109/L and age≥ 10 years were independent adverse prognostic factors for the EFS rate in children. -
Key words:
- Leukemia /
- Adrenal function /
- GC resistance /
- Prognosis
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表 1 ACTH降低组和正常组B-ALL患儿一般资料比较[M(P25,P75)]
Table 1. Comparison of general data of B-ALL children in ACTH reduced and normal group [M(P25,P75)]
类别 ACTH正常组 ACTH降低组 Z P WBC(×109/L) 12.2(3.4,32.8) 20(5.6,61.8) −2.069 0.039* HB(g/L) 81(69,104) 87(74,103) −0.954 0.340 PLT(×1012/L) 56(28,112) 52(21,97) −0.992 0.321 骨髓原始细胞(%) 64(21.8,82.3) 73.4(30,87.8) −1.477 0.140 皮质醇(nmol/L) 420(323.65,504.8) 261.5(72.5,370.5) −5.319 0.001* 年龄(岁) 5(3.6,9.2) 5(3.0,8.3) −0.220 0.826 ACTH(pg/mL) 420.3(323.6,504.8) 3.2(1.0,4.6) −9.799 0.001* 化疗次数(次) 11(7.5,11) 11(5,11) −0.095 0.924 *P < 0.05 表 2 ACTH降低组和正常组B-ALL患儿临床资料比较[n(%)]
Table 2. Comparison of clinical data of children with B-ALL in the ACTH reduced and normal groups [n(%)]
影响因素 n ACTH降低组 ACTH正常组 χ2 P 性别 0.304 0.581 男 91 46(50.5) 45(49.5) 女 63 29(46) 34(54) 年龄(岁) 0.396 0.529 < 10 122 61(50) 61(50) ≥10 32 14(43.75) 18(56.25) 民族 0.01 0.92 汉族 100 49(49) 51(51) 少数民族 54 26(48.2) 28(51.8) 白细胞分组(×109/L) 4.118 0.042* < 50 114 50(43.9) 64(56.1) ≥50 40 25(62.5) 15(50.5) MRD 4.338 0.037* 阴性 118 52(44.1) 66(55.9) 阳性 36 23(63.9) 13(36.1) GC抵抗 4.652 0.031* 阴性 109 47(43.1) 62(56.9) 阳性 45 28(62.2.5) 17(37.8) 复发 0.006 0.936 阴性 145 70(48.3) 75(51.7) 阳性 9 5(55.6) 4(44.4) 中枢神经系统白血病 1.058 0.304 阴性 143 68(47.6) 75(52.4) 阳性 11 7(63.6) 4(36.4) 睾丸浸润 0.005 0.944 阴性 147 71(48.3) 76(51.7) 阳性 7 4(57.1) 3(42.9) 死亡 0.006 0.936 阴性 145 70(48.3) 75(51.7) 阳性 9 5(55.6) 4(44.4) 病情严重程度 1.196 0.274 病重 45 25(55.6) 20(44.4) 相对平稳 109 50(45.9) 59(54.1) *P < 0.05。 表 3 ACTH重度降低组和轻度降低组B-ALL患儿一般资料比较[M(P25,P75)]
Table 3. Comparison of general data of B-ALL children with severe ACTH and mild reduction group [M(P25,P75)]
类别 ACTH重度降低组 ACTH轻度降低组 Z P WBC(×109/L) 12.2(3.4,32.8) 19.98(4.5,93.5) −0.101 0.92 HB(g/L) 81(69,104) 83(71,104.5) −0.573 0.567 PLT(×1012/L) 56(28,112) 46(20,79.25) −0.806 0.42 骨髓原始细胞(%) 72.9(25,86.5) 76.5(30,88.8) −0.711 0.477 皮质醇(nmol/L) 43.3(78.5,322.1) 300.85(254.6,419.8) −3.818 0.001* 年龄(岁) 3(4.6,8.7) 4.5(3.3,7.9) −0.738 0.461 ACTH(pg/mL) 1.17(1,2.53) 4.55(3.8,5.8) −7.506 0.001* 化疗次数(次) 11(5,11) 11(8,11) −1.319 0.187 *P < 0.05。 表 4 ACTH重度降低组和轻度降低组B-ALL患儿临床资料比较[n(%)]
Table 4. Comparison of clinical data of children with B-ALL in severe and mild ACTH reduction [n(%)]
影响因素 人数(n) ACTH重度降低组 ACTH轻度降低组 χ2 P 性别 0.001 0.97 男 46 22(47.8) 24(52.2) 女 29 14(48.3) 15(51.7) 年龄(岁) 0.028 0.868 < 10 14 7(50) 7(50) ≥10 61 29(47.5) 32(51.5) 民族 0.545 0.460 汉族 26 14(53.8) 12(46.2) 少数民族 49 22(44.9) 27(55.1) 白细胞分组(×109/L) 0.24 0.624 < 50 50 25(50) 25(50) ≥50 25 11(44) 14(56) MRD 0.555 0.456 阴性 59 27(45.8) 32(54.2) 阳性 16 9(56.25) 7(43.75) GC抵抗 0.473 0.491 阴性 28 12(42.9) 16(57.1) 阳性 47 24(51.1) 23(48.9) 复发 0.009 0.926 阴性 70 33(47.1) 37(52.9) 阳性 5 3(60) 2(40) 中枢神经系统白血病 0.012 0.911 阴性 68 32(47.1) 36(52.9) 阳性 7 4(57.1) 3(42.9) 睾丸浸润 0.356 0.551 阴性 71 33(46.5) 38(53.5) 阳性 4 3(75) 1(25) 死亡 0.009 0.926 阴性 70 33(47.1) 37(52.9) 阳性 5 3(60) 2(40) 表 5 2组间1 年、2 年EFS率比较(1)
Table 5. Comparison of 1-year and 2-year EFS rates between the two groups(1)
生存分析 n 事件数 1 a EFS率(%) 2 a EFS率(%) log-rank χ2 P ACTH降低组 75 15 78 84 0.523 0.470 ACTH正常组 79 14 82.9 87.2 表 5 2组间1 年、2 年 OS 率比较(2)
Table 5. Comparison of 1-year and 2-year OS rates between the two groups(2)
生存分析 n 事件数 1 a OS率(%) 2 a 0S率(%) log-rank χ2 P ACTH降低组 75 4 94 94 0.155 0.694 ACTH正常组 79 3 96.1 96.1 表 6 初诊B-ALL患儿的EFS单因素Cox回归(1)
Table 6. Univariate Cox regression of EFS in newly diagnosed B-ALL(1)
变量 B SE Wald P Exp(B) 95.0%CI 下限 上限 睾丸浸润 −0.086 0.729 0.014 0.907 0.918 0.220 3.831 中枢神经系统白血病 0.952 0.483 3.874 0.049* 2.590 1.004 6.681 年龄(1~10岁 vs ≥10岁) 1.048 0.351 8.925 0.003* 2.853 1.434 5.677 PLT (×1012/L) −0.004 0.003 1.726 0.189 0.996 0.990 1.002 HB (g/L) 0.004 0.007 0.344 0.558 1.004 0.990 1.019 WBC (×109/L) 0.003 0.001 10.480 0.001* 1.003 1.001 1.005 骨髓原始细胞(%) 0.002 0.006 0.107 0.744 1.002 0.991 1.013 皮质醇(nmol/L) 0.000 0.001 0.006 0.938 1.000 0.998 1.002 ACTH(pg/mL) −0.008 0.016 0.267 0.605 0.992 0.961 1.023 性别 −0.001 0.342 0.000 0.997 0.999 0.511 1.952 GC抵抗 0.305 0.357 0.731 0.393 1.357 0.674 2.730 MRD 0.383 0.387 0.977 0.323 1.466 0.686 3.133 民族 0.191 0.350 0.297 0.586 1.210 0.609 2.404 分组 −0.243 0.340 0.512 0.474 0.784 0.403 1.526 病情严重程度 0.172 0.365 0.222 0.637 1.188 0.581 2.427 白细胞分组(×109/L) 0.690 0.350 3.883 0.049* 1.994 1.004 3.962 *P < 0.05。 表 6 初诊B-ALL患儿的EFS多因素Cox回归(2)
Table 6. Multivariate Cox regression of EFS in newly diagnosed B-ALL(2)
变量 B SE Wald P Exp(B) 95.0%CI 下限 上限 年龄(1~10岁 vs ≥10岁) 0.917 0.366 6.276 0.012* 2.501 1.221 5.124 中枢神经系统白血病 0.531 0.524 1.027 0.311 1.701 0.609 4.751 WBC (×109/L) 0.003 0.001 3.989 0.046* 1.003 1.000 1.006 白细胞分组(×109/L) −0.152 0.501 0.092 0.762 0.859 0.322 2.294 *P < 0.05。 表 7 初诊B-ALL患儿的OS单因素Cox回归(1)
Table 7. Univariate Cox regression of OS in newly diagnosed B-ALL(1)
变量 B SE Wald P Exp(B) 95.0%CI 下限 上限 分组 0.322 0.764 0.178 0.673 1.380 0.309 6.168 中枢神经系统白血病 0.882 1.080 0.667 0.414 2.416 0.291 20.071 年龄(1~10岁 vs ≥10岁) 0.449 0.837 0.288 0.592 1.566 0.304 8.074 PLT (×1012/L) −0.006 0.008 0.576 0.448 0.994 0.979 1.009 HB (g/L) 0.015 0.016 0.850 0.357 1.015 0.983 1.048 WBC (×109/L) −0.002 0.005 0.215 0.643 0.998 0.988 1.007 骨髓原始细胞(%) −0.004 0.012 0.095 0.757 0.996 0.973 1.020 皮质醇(nmol/L) 0.002 0.002 1.656 0.198 1.002 0.999 1.006 ACTH(pg/mL) −0.023 0.042 0.310 0.578 0.977 0.900 1.060 性别 −1.483 1.080 1.885 0.170 0.227 0.027 1.885 GC抵抗 −0.050 0.837 0.004 0.952 0.951 0.184 4.902 MRD 1.051 0.764 1.892 0.169 2.861 0.640 12.791 民族 −0.253 0.837 0.092 0.762 0.776 0.151 4.003 睾丸浸润 −1.193 1.080 1.219 0.270 0.303 0.036 2.521 病情严重程度 −0.050 0.837 0.004 0.952 0.951 0.184 4.902 白细胞分组(×109/L) 0.186 0.837 0.050 0.824 1.205 0.234 6.210 表 7 初诊B-ALL患儿的OS多因素Cox回归(2)
Table 7. Multivariate Cox regression of OS in newly diagnosed B-ALL(2)
变量 B SE Wald P Exp(B) 95.0%CI 下限 上限 皮质醇(nmol/L) 0.002 0.002 1.464 0.226 1.002 0.999 1.006 MRD 0.807 0.772 1.090 0.296 2.240 0.493 10.181 性别 −1.361 1.089 1.562 0.211 0.257 0.030 2.167 -
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