Clinical Features and Prognosiss of Pediatric Acute Lymphoblastic Leukemia with Hyperleukocytosis
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摘要:
目的 探讨儿童高白细胞性急性淋巴细胞白血病(HL-ALL)的临床特征及预后影响因素。 方法 回顾性分析昆明市儿童医院血液肿瘤科2019年1月至2022年7月收治的427例初诊ALL患儿临床资料,以初诊白细胞计数(WBC)100×109/L为界限,分为高白组92例与非高白组335例,比较2组间的临床特征、主要实验室检查指标、总生存时间(OS)、无事件生存时间(EFS)等。 结果 427例ALL患儿中,男性250例,女性177例,男女比例1.41∶1,高白组92例(21.5%),非高白组335例(78.5%)。与非高白组相比,高白组患儿年龄<1岁和>10岁、T淋巴细胞白血病(T-ALL)、中重度肝脾肿大、危险度为高危的比例更高(P < 0.05),初诊幼稚细胞百分比、血尿酸(UA)水平、血乳酸脱氢酶(LDH)水平更高(P < 0.05),初诊血小板计数(PLT)水平以及合并超二倍体的比例低(P < 0.05)。高白组的3 a EFS及OS均低于非高白组,多因素回归分析显示,初诊白细胞计数≥100×109/L、年龄>10岁、年龄<1岁、T-ALL、高危、D15 MRD阳性、D33 MRD阳性、CNSL、MLL重排阳性、MEF2D重排阳性是影响ALL患儿EFS率及OS率的独立危险因素(P < 0.05)。 结论 HL-ALL患儿初诊时普遍存在显著外周血幼稚百分比更高,血UA及血LDH升高,并且常伴有发病年龄<1岁或>10岁、T-ALL、肝脾肿大、高危,高白组患儿早期治疗反应欠佳,预后不良。 Abstract:Objective To investigate the clinical features and prognostic factors of pediatric acute lymphoblastic leukemia with hyperleukocytosis (HL-ALL). Methods The clinical data of 427 newly diagnosed ALL children admitted to the Department of Hematology and Oncology of Kunming Children’ s Hospital from January 2019 to July 2022 were retrospectively analyzed. According to the initial white blood cell count (WBC) of 100×109/L, the children were divided into the hyperleukocytosis group and the non-hyperleukocytosis group. The clinical characteristics, major laboratory tests, overall survival (OS) and event-free survival (EFS) were compared between the two groups. Results There were 250 males and 177 females, with a male-to-female ratio of 1.41∶1. There were 92 cases (21.5%) in the hyperleukocytosis group and 335 cases (78.5%) in the non-hyperleukocytosis group. Compared with the non-hyperleukocytosis group, the hyperleukocytosis group had significantly higher proportions of children aged < 1 year and > 10 years, T lymphoblastic leukemia (T-ALL), moderate to severe hepatosplenomegaly, and high-risk risk (P < 0.05), as well as significantly higher percentage of immature cells at initial diagnosis, serum uric acid (UA) level, and lactate dehydrogenase (LDH) level (P < 0.05). The platelet count (PLT) and the proportion of hyperdiploidy at diagnosis were lower (P <0.05). The 3-year EFS and OS of the hyperleukocytosis group were lower than those of the non-hyperleukocytosis group. WBC ≥100×109/L at diagnosis, age >10 years, age < 1 year, T-ALL, high-risk, D15 MRD positive, D33 MRD positive, CNSL, MLL rearrangement, and MEF2D rearrangement were independent risk factors for EFS and OS rates in children with ALL (P < 0.05). Conclusion The children with HL-ALL usually have a higher percentage of peripheral blood immature cells, elevated serum UA and LDH, and are often accompanied by age of onset <1 or > 10 years old, T-ALL, hepatosplenomegaly, and high risk. The early treatment response and prognosis of the children with HL-ALL are poor. -
Key words:
- Acute lymphoblastic leukemia /
- Hyperleukocytosis /
- Children
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表 1 高白组与非高白组的临床特征比较 [n(%)]
Table 1. Comparison of clinical characteristics between the high leukocyte and non-high leukocyte groups [n(%)]
变量 高白组(n=92) 非高白组(n=335) χ2 P 性别 男 56(60.9) 194(57.9) 0.260 0.610 女 36(39.1) 141(42.1) 年龄分组(岁) <1 5(5.4) 6(1.8) 21.322 <0.001* 1~10 52(56.5) 273(81.5) >10 35(38.1) 56(16.7) 民族 汉族 62(67.4) 217(64.8) 0.218 0.641 少数民族 30(32.6) 118(35.2) 肝脏肿大 无或轻度 35(38) 176(52.5) 6.066 0.014* 中重度 57(62) 159(47.5) 脾脏肿大 无或轻度 39(42.4) 232(69.3) 22.462 <0.001* 中重度 53(57.6) 103(30.7) 睾丸浸润 无 55(98.2) 189(97.4) - 1.000 有 1(1.8) 5(2.6) CNSL 无 86(93.5) 328(97.9) 3.419 0.064 有 6(6.5) 7(2.1) 免疫分型 B-ALL 48(52.2) 299(89.3) 65.180 <0.001* T-ALL 44(47.8) 36(10.7) 染色体核型 正常 28(30.4) 80(23.9) 17.119 <0.001* 超二倍体 1(1.1) 49(14.6) 亚二倍体 1(1.1) 4(1.2) 结构异常 62(67.4) 202(60.3) *P < 0.05。 表 2 高白组与非高白组的初诊血常规比较 [M(P25,P75)]
Table 2. Comparison of initial blood routine between the high leukocyte and non-high leukocyte groups[M(P25,P75)]
变量 高白组(n=92) 非高白组(n=335) Z P WBC(×109/L) 232.11(134.31,406.26) 8.04(3.62,26.92) −14.698 <0.001* Hb(g/L) 79.5(60,103.25) 78(66,94) −0.158 0.875 PLT(×109/L) 36.5(20.25,54) 55(24,102) −3.701 <0.001* 初诊幼稚细胞百分比(%) 80.5(72,86) 24(4,52) −11.980 <0.001* UA/ULN 1.21(0.97,1,56) 0.81(0.65,0.99) −9.177 <0.001* LDH/ULN 3.25(1.63,5.91) 0.85(0.52,1.52) −9.913 <0.001* *P < 0.05。 表 3 外周血幼稚细胞百分比、UA/ULN、LDH/ULN与初诊WBC计数相关性比较
Table 3. Comparison of correlation of peripheral blood immature cells,UA / ULN,LDH / ULN and WBC count
变量 总体(n=427) 高白组(n=92) 非高白组(n=335) rs P rs P rs P 幼稚细胞百分比 0.814 <0.001* 0.121 0.252 0.74 <0.001* 初诊UA/ULN 0.504 <0.001* 0.228 0.029* 0.318 <0.001* 初诊LDH/ULN 0.613 <0.001* 0.395 <0.001* 0.451 <0.001* rs:相关系数(>0.7表示高度正相关,>0.4表示中度正相关,0~0.4表示低度正相关);*P < 0.05。 表 4 B-ALL患儿主要融合基因比较[n(%)]
Table 4. Comparison of the major fusion genes in B-ALL children [n(%)]
融合基因 高白组(n=48) 非高白组(n=299) χ2 P TEL-AML1+ 3(6.3) 38(12.7) 1.656 0.237 E2A-PBX1+ 6(12.5) 28(9.4) 0.174 0.677 MLL重排 11(22.9) 12(4.0) 20.924 <0.001* BCR-ABL1+ 13(27.1) 18(6.0) 20.040 <0.001* *P < 0.05。 表 5 T-ALL患儿主要融合基因比较[n(%)]
Table 5. Comparison of the major fusion genes in T-ALL children [n(%)]
融合基因 高白组(n=44) 非高白组(n=36) χ2 P SIL-TAL1+ 18(40.9) 3(8.3) 10.853 0.001* NOTCH1+ 22(81.5) 10(76.9) 0.000 1.000 FBXW7+ 11(40.7) 1(7.7) 3.126 0.077 *P < 0.05。 表 6 高白组与非高白组治疗反应与危险度分层 [n(%)]
Table 6. Treatment response and risk stratification between the high leukocyte and non-high leukocyte groups [n(%)]
诱导治疗反应 高白组(n=83) 非高白组(n=323) χ2 P MRD D15 MRD阳性 21(25.3) 44(13.6) 6.698 0.01* D33 MRD阳性 10(12.0) 32(9.9) 0.326 0.568 危险度 中危 42(50.6) 244(75.5) 19.726 <0.001* 高危 41(49.4) 79(24.5) *P < 0.05。 表 7 ALL患儿EFS和OS的单因素分析
Table 7. Univariate analysis of EFS and OS in children with ALL
影响因素 EFS OS HR(95%CI) P HR(95%CI) P 初诊WBC计数
(<100×109/L vs>100×109/L)2.32(1.41~3.82) 0.001* 2.68(1.53~4.70) 0.001* 年龄分组 1~10岁 vs >10岁 3.09(1.89~5.09) <0.001* 4.45(2.52~7.84) <0.001* 1~10岁 vs <1岁 6.08(2.38~15.51) <0.001* 4.90(1.47~16.35) 0.010* 性别(女vs男) 1.07(0.66~1.74) 0.783 1.27(0.72~2.23) 0.417 免疫分型(B-ALL vs T-ALL) 2.54(1.54~4.21) <0.001* 3.75(2.15~6.54) <0.001* 危险度(中位vs 高危) 4.57(2.75~7.59) <0.001* 4.76(2.63~8.64) <0.001* D15 MRD 3.10(1.85~5.20) <0.001* 3.71(2.06~6.69) <0.001* D33 MRD 3.54(2.03~6.17) <0.001* 4.23(2.26~7.91) <0.001* 初诊CNSL 3.65(1.47~9.10) 0.005* 4.72(1.87~11.91) 0.001* BCR-ABL1 1.73(0.83~3.63) 0.144 1.74(0.74~4.07) 0.205 E2A-PBX1 0.16(0.02~1.18) 0.073 0.04(0.00~3.50) 0.162 TEL-AML1 0.04(0.00~1.35) 0.073 0.04(0.00~2.40) 0.125 MLL重排 2.42(1.20~4.88) 0.014* 2.48(1.12~5.50) 0.026* SIL-TAL1 1.27(0.46~3.48) 0.647 1.72(0.62~4.77) 0.300 MEF2D重排 4.98(1.81~13.72) 0.002* 6.57(2.36~18.28) <0.001* CRLF2重排或过表达 0.98(0.39~2.43) 0.960 1.05(0.38~2.92) 0.921 *P < 0.05。 表 8 ALL患儿EFS及OS的多因素分析
Table 8. Multivariate analysis of EFS and OS in children with ALL
影响因素 EFS OS HR(95%CI) P HR(95%CI) P 初诊WBC计数
(<100×109/L vs >100×109/L)2.32(1.41~3.82) 0.001* 2.68(1.53~4.70) 0.001* 年龄分组 1~10岁 vs >10岁 3.09(1.89~5.09) <0.001* 4.45(2.52~7.84) <0.001* 1~10岁 vs <1岁 6.08(2.38~15.51) <0.001* 4.90(1.47~16.35) 0.010* 免疫分型(B-ALL vs T-ALL) 2.54(1.54~4.21) <0.001* 3.75(2.15~6.54) <0.001* 危险度(中危 vs 高危) 4.57(2.75~7.59) <0.001* 4.76(2.63~8.64) <0.001* D15 MRD 3.10(1.85~5.20) <0.001* 3.71(2.06~6.69) <0.001* D33 MRD 3.54(2.03~6.17) <0.001* 4.23(2.26~7.91) <0.001* 初诊CNSL 3.65(1.47~9.10) 0.005* 4.72(1.87~11.91) 0.001* MLL重排 2.42(1.20~4.88) 0.014* 2.48(1.12~5.50) 0.026* MEF2D重排 4.98(1.81~13.72) 0.002* 6.57(2.36~18.28) <0.001* *P < 0.05。 -
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