Correlation of Mean Corpuscular Volume with Clinical Features and Prognosis of Patients with Treatment-Related Acute Myeloid Leukemia
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摘要:目的
探讨平均红细胞体积（MCV）与治疗相关急性髓系白血病（t-AML）患者临床特点及预后的相关性。
方法回顾性分析41例t-AML患者的临床和实验室资料，根据MCV中位数将其分为低MCV组（LMCV组）和高MCV组（HMCV组）。采用Spearman秩相关分析，采用Kaplan-Meier法绘制生存曲线，组间比较采用Log-rank检验，多因素分析采用Cox比例风险回归模型。
结果G-CSF治疗史与t-AML患者MCV成正相关（r=0.325，P<0.05）。与HMCV组相比，LMCV组患者外周血红细胞计数（RBC）和血红蛋白浓度（HGB）及PML-RARa融合基因阳性率更高（P<0.05），而淋系抗原CD7和CD56的表达率更低（P<0.05）。LMCV组患者治疗效果、OS和RFS均优于HMCV组（P<0.05）。未达到CR是影响t-AML患者OS的独立危险因素（P=0.002），而MCV≥98.9 fl虽然是影响t-AML患者OS和RFS的不良因素（P<0.1），但不是独立危险因素（P>0.05）。
结论MCV水平不同的t-AML患者有不同的临床特点，高MCV患者治疗效果和预后均较差。
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关键词:
- 平均红细胞体积 /
- 治疗相关急性髓系白血病 /
- 临床特点 /
- 预后
Abstract:ObjectiveTo analyze the correlation of mean corpuscular volume (MCV) with clinical features and the prognosis of patients with treatment-related acute myeloid leukemia (t-AML).
MethodsThe clinical and laboratory data of 41 patients with t-AML were retrospectively analyzed. The patients were divided into LMCV and HMCV groups. Spearman’s rank correlation was used for correlation analysis, and a survival curve was drawn via Kaplan-Meier method. Log-rank test was used for comparison between groups, and Cox proportional risk regression model was used for multivariate analysis.
ResultsThe treatment history of G-CSF was positively correlated with the MCV of patients with t-AML (correlation coefficient r=0.325, P<0.05). The amount of RBC and HGB in the peripheral blood of patients and the percentage of PML-RARa positive in the LMCV group were significantly higher than those in the HMCV group, and the percentages of the expression levels of lymphoid antigen CD7 and CD56 were significantly lower than those in the HMCV group (P<0.05). The therapeutic effect, OS, and RFS of the LMCV group were better than those of the HMCV group (P<0.05). Failure to reach CR was an independent risk factor for OS of patients with t-AML (HR=0.053, P=0.002), and MCV≥98.9 fl was an adverse factor for OS and RFS of patients with t-AML (P<0.1) but not an independent risk factor (P>0.05).
ConclusionPatients with t-AML with different levels of MCV have different clinical characteristics, and patients with high MCV have poor therapeutic effect and prognosis.
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0 引言
平均红细胞体积（Mean corpuscular volume, MCV）是指外周血红细胞体积的平均值，它对红细胞体积变化具有较高的敏感性[1]。有研究[2]显示MCV的升高与衰老、营养不良和酗酒等因素相关，尤其以老年患者更为常见，被认为是慢性疾病患者生存预后的预测因子；也有研究[3]认为MCV可作为健康人群的独立生存预测指标。值得注意的是，多项国内外研究[3-7]表明，高MCV与食管癌、结直肠癌、胃癌和肝癌等实体肿瘤患者的不良预后密切相关。然而，目前关于MCV与治疗相关急性髓系白血病（Treatment-related acute myeloid leukemia, t-AML）临床特点、治疗效果及预后关系的研究较为匮乏，本研究回顾性分析了我院收治的t-AML患者的临床和实验室数据，旨在探讨MCV水平与此类患者临床特征及预后的相关性，希望能为t-AML的个体化诊疗提供新的思路和依据。
1 资料与方法
1.1 研究对象
回顾性收集2016年1月至2023年12月郑州大学附属肿瘤医院血液科收治的t-AML住院患者41例，其中男性12例，女性29例，中位年龄56.0（45.5~62.5）岁。t-AML的诊断标准参照2016版的《WHO髓系肿瘤和白血病分类》[8]。纳入标准：（1）骨髓形态学、免疫分型、细胞遗传学和分子遗传学检测结果完整；（2）原发肿瘤经组织病理检查证实，并按照相关指南进行规范治疗；（3）临床资料完整。排除标准：（1）对AML治疗药物过敏者；（2）肝、肾功能严重异常者。根据患者外周血红细胞MCV中位数（98.9 fl）将患者分为低MCV组（LMCV组）19例和高MCV组（HMCV组）22例。
1.2 研究方法
资料收集：通过医院电子病历系统和实验室数据管理系统收集t-AML患者的临床资料和实验室检查结果。
治疗方案：根据t-AML分型和患者自身情况制定个体化治疗方案。治疗相关急性早幼粒细胞白血病（Acute promyelocytic leukemia, t-APL）患者采用全反式维甲酸联合砷剂诱导化疗；治疗非t-APL患者采用地西他滨＋阿柔比星＋阿糖胞苷＋粒细胞集落刺激因子、高三尖杉酯碱＋阿糖胞苷＋粒细胞集落刺激因子、柔红霉素＋阿糖胞苷等方案化疗。所有患者缓解后均接受巩固治疗，并进行中枢神经系统白血病（Central nervous system leukemia, CNSL）预防性治疗。部分患者缓解后接受自体或异基因造血干细胞移植（Hematopoietic stem cell transplantation, HSCT）。
疗效评价标准：完全缓解（Complete remission, CR）、形态学完全缓解而血细胞计数未完全缓解（Incomplete remission, CRi）、部分缓解（Partial remission, PR）、治疗失败[9]。
随访：从医院信息管理系统中查询入组患者的联系方式，以患者确诊为t-AML日期作为随访的开始日期，患者的死亡日期作为随访的终点，随访时间截止到2024年9月30日。比较不同组别患者总生存期（Overall survival, OS）和无复发生存期（Relapse-free survival, RFS）数据。OS为患者确诊为t-AML日期到患者死亡日期或随访截止日期，随访期间电话联系3次未接通定义为失访，失访病例不在本研究之内。本研究经河南省肿瘤医院伦理委员会批准通过，并得到患者或其家属知情同意（伦理批准号：2019342）。
1.3 统计学方法
采用SPSS25.0软件进行数据分析。计量资料符合正态分布者以均数±标准差表示，组间比较采用Student's t检验，不符合正态分布者使用非参数秩和检验，以中位数（25%~75%）形式描述。计数资料以百分率（%）表示，组间比较采用卡方检验。采用Spearman秩相关进行相关性分析。采用Kaplan-Meier法绘制生存曲线，组间比较采用Log-rank检验。将单因素分析P<0.1的变量纳入多因素分析，多因素分析采用Cox比例风险回归模型，P<0.05为差异有统计学意义。
2 结果
2.1 t-AML患者MCV与原发肿瘤治疗的相关性
结果显示，t-AML患者确诊时MCV水平仅与原发肿瘤粒细胞集落刺激因子治疗史具有正相关性（P=0.038），见表1。
表 1 t-AML患者MCV与原发肿瘤治疗的相关性分析Table 1 Correlation analysis of MCV in patients with t-AML and the treatment of primary tumorsComparison indicators (yes/no) n Proportion r P Lymphoma 13 (31.7%) 0.018 0.912 Breast cancer 13 (31.7%) −0.018 0.912 Malignant tumor of
reproductive system7 (17.1%) 0.301 0.056 Digestive system malignancy 4 (9.8%) 0.007 0.966 Lung cancer 2 (4.9%) −0.297 0.060 Other systemic malignancies 2 (4.9%) −0.239 0.132 Alkylating agent 38 (92.7%) 0.285 0.071 Topoisomerase Ⅱ inhibitors 27 (65.9%) 0.120 0.456 Antimetabolites 21 (51.2%) 0.186 0.245 Botanical drug 23 (56.1%) 0.085 0.596 Endocrine drug 1 (2.4%) 0.167 0.296 Granulocyte colony-stimulating
factor38 (92.7%) 0.325 0.038 Radiotherapy 14 (34.1%) 0.221 0.099 2.2 LMCV组和HMCV组患者基线资料及实验室检查结果比较
结果显示，与HMCV组相比，LMCV组患者外周血红细胞计数（RBC）和血红蛋白浓度（HGB）更高（P<0.05），PML-RARa融合基因阳性率更高（42.1% vs. 9.1%，P=0.037），见表2。
表 2 LMCV组和HMCV组患者基线资料及实验室检查结果比较Table 2 Comparison of baseline data and laboratory test results between the LMCV group and the HMCV groupContrast index Overall situation LMCV group (n=19) HMCV group (n=22) Statistical value P Gender (male/female, n) 12 (29.3%)/29 (70.7%) 6 (31.6%)/13 (68.4%) 6 (27.3%)/16 (72.7%) 0.091 0.763a Age (years) 53.4±12.7 50.6±14.9 55.9±10.3 1.351 0.184b Onset interval (month) 21.0 (16.5-46.0) 21.0 (18.0-43.0) 28.0 (17.6-53.3) 191.000 0.638c WBC (×109/L) 6.9 (1.5-27.9) 3.2 (1.4-19.7) 8.1 (2.0-33.8) 175.000 0.374c RBC (×1012/L) 2.5±0.8 2.9±0.7 2.1±0.6 3.977 <0.001 HGB (g/L) 80.7±21.1 91.7±20.4 71.1±17.0 3.515 0.001b PLT (×109/L) 32.0 (17.0-59.5) 33.0 (20.0-62.0) 30.0 (14.5-49.3) 179.500 0.440c Proportion of bone marrow
blast cells62.4% (36.5%-83.8%) 78.2% (39.0%-87.8%) 53.7% (37.4%-82.7%) 161.500 0.214c Proportion of peripheral
blood original cells27.0% (8.5%-75.0%) 28.0% (7.0%-88.0%) 24.5% (8.8%-61.8%) 189.000 0.601c LDH(U/L) 286.0 (203.0-662.0) 286.0 (201.0-613.0) 288.5 (198.8-832.0) 204.500 0.906c Chromosomal prognostic
stratification (n)2.213 0.331a Well 14 (34.1%) 8 (42.1%) 6 (27.3%) Medium 19 (46.3%) 9 (47.4%) 10 (45.5%) Poor 8 (19.5%) 2 (10.5%) 6 (27.3%) PML-RARa positive (yes/no, n) 10 (24.4%) 8 (42.1%)/11 (57.9%) 2 (9.1%)/20 (90.9%) 4.368 0.037a MLL gene fracture
rearrangement (yes/no, n)5 (12.2%) 2 (10.5%)/17 (89.5%) 3 (13.6%)/19 (86.4%) 0.000 >0.999a AML-ETO positive (yes/no, n) 3 (7.3%) 0 (0.0%)/19 (100.0%) 3 (13.6%)/19 (86.4%) 1.146 0.284a Notes: a: Chi-square test; b: Student’s t test; c: nonparametric rank sum test; WBC: white blood cell; RBC: red blood corpuscle; HGB: hemoglobin; PLT: platelets; LDH: lactate dehydrogenase; PML-RARa: promyelocytic leukemia-retinoic acid receptor alpha; MLL: mixed lineage leukemia; AML-ETO: acute myelogenous leukemia-ETO. 2.3 LMCV组和HMCV组患者免疫表型及FAB分型比较
结果显示，LMCV组患者淋系抗原CD7和CD56的表达率显著低于HMCV组，而FAB分型中APL的比例显著高于HMCV组（均P<0.05），见表3。
表 3 LMCV组和HMCV组患者免疫表型及FAB分型比较Table 3 Comparison of immunophenotype and FAB typing between LMCV group and HMCV groupContrast index (yes/no, n) Proportion LMCV group (n=19) HMCV group (n=22) Statistical value P CD2 positive 6 (14.6%) 2 (10.5%)/17 (89.5%) 4 (18.2%)/18 (81.8%) 0.062 0.804 CD7 positive 10 (24.4%) 1 (5.3%)/18 (94.7%) 9 (40.9%)/13 (59.1%) 5.225 0.022 CD19 positive 4 (9.8%) 1 (5.3%)/18 (94.7%) 3 (13.6%)/19 (86.4%) 0.139 0.409 CD56 positive 9 (22.0%) 1 (5.3%)/18 (94.7%) 8 (36.4%)/14 (63.6%) 4.048 0.043 CD10 positive 1 (2.4%) 0 (0.0%)/19 (100.0%) 1 (4.5%)/21 (95.5%) 0.000 >0.999 CD4 positive 6 (14.6%) 2 (10.5%)/17 (89.5%) 4 (18.2%)/18 (81.8%) 0.062 0.804 CD25 positive 4 (9.8%) 2 (10.5%)/17 (89.5%) 2 (9.1%)/20 (90.9%) 0.000 >0.999 M2a 1 (2.4%) 0 (0.0%)/19 (100.0%) 1 (4.5%)/21 (95.5%) 0.000 >0.999 M2b 2 (4.9%) 0 (0.0%)/19 (100.0%) 2 (9.1%)/20 (90.9%) 0.385 0.525 APL 10 (24.4%) 8 (42.1%)/11 (57.9%) 2 (9.1%)/20 (90.9%) 4.368 0.037 M4 11 (26.8%) 6 (31.6%)/13 (68.4%) 5 (22.7%)/17 (77.3%) 0.407 0.524 M5 16 (39.0%) 5 (26.3%)/14 (73.7%) 11 (50.0%)/11 (50.0%) 2.403 0.121 2.4 LMCV组和HMCV组患者基因突变对比分析
LMCV组和HMCV组患者基因突变结果中，28例（68.3%）基因突变阳性，其中ABCB1突变13例（31.7%），FLT3-ITD突变9例（22.0%），FLT3-TKD和TET2突变5例（12.2%），RAS突变4例（9.8%）、CYP2C19突变3例（7.3%），IDH2、KIT、TP53、PTEN和DNMT3A突变各2例（4.9%），ASXL1、CBL、RUNX1、NOTCH1和BCOR突变各1例（2.4%）。通过卡方分析，LMCV组和HMCV组患者这些基因突变的差异均无统计学意义（均P>0.05）。
2.5 LMCV组和HMCV组患者治疗效果和预后分析
41例t-AML患者中，放弃治疗5例（12.2%），接受正规化疗36例（87.8%）。接受正规化疗的患者中，达到CR 19例（52.8%），达到CRi 5例（13.9%），达到PR 3例（8.3%），未缓解9例（25.0%）。至随访结束，24例（66.7%）达到CR和CRi的患者中，t-AML复发6例（25.0%），中位RFS为32.0个月。36例接受治疗患者中24例（66.7%）死亡，其中13例（31.7%）死于疾病进展，7例（19.4%）死于感染，2例（5.6%）死于脑出血，死于DIC和心肺衰竭各1例（2.8%）；12例（29.3%）持续存活，中位OS为9.0个月。
接受正规治疗的36例t-AML患者中，LMCV组16例，HMCV组20例，两组获得CR的患者分别为12例（75.0%）和7例（35.0%）（χ2=5.096，P=0.024）；LMCV组中位OS为69.0个月，HMCV组中位OS为8.0个月，通过Log-rank检验发现，LMCV组患者OS明显高于HMCV组（χ2=4.931，P=0.026），见图1A。在达到CR和CRi的24例患者中，LMCV组11例，HMCV组13例，LMCV组中位RFS为80.0个月，HMCV组中位RFS为9.0个月，通过Log-rank 检验，LMCV组患者RFS明显高于HMCV组（χ2=8.700，P=0.003），见图1B。
为进一步排除t-APL对预后的影响，本研究对11例LMCV组患者和20例HMCV组非t-APL患者的治疗效果和预后进行了亚组分析。结果显示，两组分别有3例（37.5%）和7例（38.9%）达到CR（χ2=0.000，P>0.999）。LMCV组患者中位OS和RFS分别为2和68个月，HMCV组患者中位OS和RFS均为8个月。两组患者OS和RFS的差异均无统计学意义（χ2=0.006，P=0.937；χ2=1.651，P=0.199），见图2。
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图 2 无APL的LMCV组和HMCV组OS (A)和RFS (B)分析Figure 2 OS (A) and RFS (B) in LMCV group and HMCV group without APL2.6 影响t-AML患者OS和RFS的预后因素分析
单因素分析结果显示，RBC<2.3×109/L、HGB<77.0 g/L、MCV≥98.9 fl、骨髓原始细胞<62.4%、非染色体预后分层良好、非PML-RARa阳性、CBL突变阳性、未达到CR、原发肿瘤为淋巴瘤和消化系统恶性肿瘤、CD56阳性、非APL型、非M5型是影响t-AML患者OS和RFS的不良因素，有抗代谢药治疗史、M4型是影响t-AML患者OS的不良因素，而WBC≥6.9×109/L、PLT<32.0×109/L、MLL基因断裂重排和CD4阳性是影响t-AML患者RFS的不良因素（均P<0.1），见表4。将单因素分析中P<0.1的变量纳入Cox比例风险回归模型进行多因素分析，结果显示，未达到CR是影响t-AML患者OS的独立危险因素（HR=0.053，P=0.002），而MCV≥98.9 fl虽然是影响t-AML患者OS和RFS的不良因素，但不是独立危险因素（OS: HR=1.009，P=0.869；RFS: HR=1.010，P=0.950）。
表 4 影响t-AML患者预后的单因素分析Table 4 Analysis of single factors affecting the prognosis of patients with t-AMLInfluence factor OS RFS n χ2 P n χ2 P WBC (<6.9/≥6.9, ×109/L) - - - 11/13 5.019 0.025 RBC (<2.3/≥2.3, ×109/L) 16/20 7.716 0.005 11/13 13.312 <0.001 HGB (<77.0/≥77.0, g/L) 17/19 6.858 0.009 12/12 13.513 <0.001 MCV (<98.9/≥98.9, fl) 16/20 4.931 0.026 11/13 8.700 0.003 PLT (<32.0/≥32.0, ×109/L) - - - 10/14 3.100 0.078 Bone marrow blast cells (<62.4%/≥62.4%) 17/19 6.570 0.010 10/14 5.151 0.023 Well chromosomal prognostic stratification (yes/no, n) 14/22 6.816 0.009 12/12 5.694 0.017 PML-RARa positive (yes/no, n) 10/26 7.836 0.005 9/15 7.562 0.006 MLL gene fracture rearrangement (yes/no, n) - - - 2/22 4.448 0.035 CR (yes/no, n) 19/17 24.068 <0.001 19/5 11.826 0.001 Primary tumor being lymphoma 11/25 4.664 0.031 5/19 6.324 0.012 Primary tumor being malignant tumor of digestive system 3/33 19.727 <0.001 1/23 5.000 0.025 Antimetabolite 3/33 3.081 0.079 - - - CD56 positive (yes/no, n) 8/18 5.561 0.018 4/20 6.243 0.012 CD4 positive (yes/no, n) - - - 3/21 6.073 0.014 APL positive (yes/no, n) 10/26 7.836 0.005 9/15 7.562 0.006 M4 positive (yes/no, n) 7/29 3.049 0.081 - - - M5 positive (yes/no, n) 15/21 2.994 0.084 9/15 8.970 0.003 CBL mutation positive (yes/no, n) 1/35 6.200 0.013 1/23 5.000 0.025 Notes: -: no statistics have been calculated as all cases have been excluded; MCV: mean corpuscular volume; CR: complete remission; CBL: casitas B-lineage lymphoma. 3 讨论
t-AML是指因肿瘤性或非肿瘤性疾病接受细胞毒药物化疗和（或）放疗后发生的AML。根据致病因素的不同，可分为烷化剂相关性和拓扑异构酶Ⅱ（TopoⅡ）抑制剂相关性两大类：第一类t-AML常伴有遗传物质的非平衡丢失，多涉及5号或7号染色体；第二类则常伴有涉及11q23或21q22染色体的平衡易位，如t（9；11）（p21；q23）、t（11；19）（q23；p13）和t（8；21）（q22；q22）等[10]。目前，t-AML的发病机制尚未完全阐明。有研究[11]显示，染色体易位诱导的癌基因融合可能导致基因组不稳定，或直接选择现存的耐药造血细胞进行克隆，从而参与t-AML的发生发展。有研究[12]在初诊且未接受治疗的患者外周血和（或）骨髓中检测到白血病前期异常克隆性造血，提示化疗或放疗可能只是t-AML发生的诱发因素。本研究发现有G-CSF治疗史与t-AML患者MCV水平呈正相关，提示G-CSF治疗可能导致患者红细胞体积增大，但具体的相关机制有待于进一步的研究。
Sasaki等[13]的研究显示，淋巴瘤是继发t-AML中最常见的原发性恶性肿瘤，其次是乳腺癌。本研究中，原发肿瘤为淋巴瘤和乳腺癌的患者各占31.7%，而生殖系统、消化系统、呼吸系统和其他系统恶性肿瘤分别占17.1%、9.8%、4.9%和4.9%，与Sasaki等的研究结果基本一致。然而，相关性分析未发现原发肿瘤类型与t-AML患者MCV水平相关。关于t-AML的发病时间，Godley等[14]认为原发肿瘤与发生t-AML的间隔期从数月到数年不等，可能与放化疗的累积剂量、强度和类型有关。Kayser等[15]的研究发现，从原发肿瘤到t-AML发生的潜伏期通常为4~6年，中位发病年龄为57~61岁。本研究中位发病间隔为21个月，明显低于Godley等的结果，而中位年龄56岁与之基本一致。但LMCV组和HMCV组患者在发病间隔和年龄方面差异无统计学意义。本研究还对LMCV组和HMCV组患者的基线特征及实验室指标的差异进行了对比分析，发现LMCV组患者外周血RBC和HGB明显高于HMCV组患者。有研究[10]认为，某些基因的多态性或突变与t-AML相关，且是接受化疗患者发生t-AML的潜在危险因素。研究[16]表明，细胞遗传学异常和潜在的遗传异常可能是影响t-AML预后的重要因素。与原发AML（p-AML）相比，t-AML通常预后较差，具有更高比例的不良细胞遗传学异常和不利突变。欧洲白血病网指南依据白血病细胞遗传学和分子遗传学特征将AML分为预后良好、中等以及不良三组[17]。但本研究未发现LMCV组和HMCV组患者在预后分层方面有明显的差异。在分子遗传学特征方面，本研究发现LMCV组患者PML-RARa融合基因阳性率明显高于HMCV组。关于免疫表型，孙幸等[18]的研究显示AML患者跨系表达CD7、CD19、CD56、CD4等较为常见；而宋明珠[19]的研究认为t-AML患者淋系抗原表达以CD7、CD56和CD4为主。本研究与上述文献结果基本一致，且发现LMCV组患者CD7和CD56表达率明显低于HMCV组。Rai等[20]的研究表明，CD7和CD56在AML患者中的表达具有预后意义，且与微小残留病变、高风险和较短的总体生存期等不良预后因素相关。综上，可以推测LMCV组患者的治疗效果和预后可能优于HMCV组，然而，MCV能否作为t-AML的临床预后指标，仍需更多的临床数据来证实。
吴荣娟等[21]的研究认为t-AML患者预后较差，其疗效与患者的一般状态、分子生物学特点、既往化疗的疗程数及是否存在高危不良预后因素等有关；Samra等[22]的研究发现，t-AML患者RFS和OS均较差。Takeyama等[23]的研究显示，在256例t-AML患者中，有72%接受了常规抗白血病方案化疗，其中46%获得完全缓解，中位OS为9.7个月。本研究结果与Takeyama等的报道基本一致，并发现LMCV组患者治疗效果和预后均优于HMCV组。值得注意的是，既往研究[24]显示t-APL预后与原发APL相似，是t-AML中预后较好的亚型。本研究发现，排除t-APL患者后，LMCV组与HMCV组患者OS和RFS的差异均无统计学意义，提示LMCV组患者治疗效果和预后优于HMCV组可能与t-APL比例较高有关。宋丽敏等[25]的研究结果显示，在新诊断的多发性骨髓瘤患者中，由HGB、PLT和MCV组成的造血评分系统是影响患者OS的预后因素之一，其中MCV是独立危险因素。然而，本研究单因素和多因素分析显示，未达到CR是影响t-AML患者OS的独立危险因素，而MCV≥98.9 fl虽然是影响t-AML患者OS和RFS的不良因素，但不是独立危险因素。
综上，本研究得出，G-CSF治疗史与t-AML患者MCV水平呈正相关。LMCV组患者外周血RBC和HGB及PML-RAR融合基因阳性率明显高于HMCV组，而淋系抗原CD7和CD56的表达率更低。LMCV组患者治疗效果和预后优于HMCV组，但排除t-APL患者后，两组间差异无统计学意义。未达到CR是影响t-AML患者OS的独立危险因素，而MCV≥98.9 fl虽与不良预后相关，但并非独立危险因素。
Competing interests: The authors declare that they have no competing interests.利益冲突声明：所有作者均声明不存在利益冲突。作者贡献：吕晓娴：数据收集和分析、撰写论文许青霞：指导研究方案、修改论文 -
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图 2 无APL的LMCV组和HMCV组OS (A)和RFS (B)分析
Figure 2 OS (A) and RFS (B) in LMCV group and HMCV group without APL
表 1 t-AML患者MCV与原发肿瘤治疗的相关性分析
Table 1 Correlation analysis of MCV in patients with t-AML and the treatment of primary tumors
Comparison indicators (yes/no) n Proportion r P Lymphoma 13 (31.7%) 0.018 0.912 Breast cancer 13 (31.7%) −0.018 0.912 Malignant tumor of
reproductive system7 (17.1%) 0.301 0.056 Digestive system malignancy 4 (9.8%) 0.007 0.966 Lung cancer 2 (4.9%) −0.297 0.060 Other systemic malignancies 2 (4.9%) −0.239 0.132 Alkylating agent 38 (92.7%) 0.285 0.071 Topoisomerase Ⅱ inhibitors 27 (65.9%) 0.120 0.456 Antimetabolites 21 (51.2%) 0.186 0.245 Botanical drug 23 (56.1%) 0.085 0.596 Endocrine drug 1 (2.4%) 0.167 0.296 Granulocyte colony-stimulating
factor38 (92.7%) 0.325 0.038 Radiotherapy 14 (34.1%) 0.221 0.099 
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表 2 LMCV组和HMCV组患者基线资料及实验室检查结果比较
Table 2 Comparison of baseline data and laboratory test results between the LMCV group and the HMCV group
Contrast index Overall situation LMCV group (n=19) HMCV group (n=22) Statistical value P Gender (male/female, n) 12 (29.3%)/29 (70.7%) 6 (31.6%)/13 (68.4%) 6 (27.3%)/16 (72.7%) 0.091 0.763a Age (years) 53.4±12.7 50.6±14.9 55.9±10.3 1.351 0.184b Onset interval (month) 21.0 (16.5-46.0) 21.0 (18.0-43.0) 28.0 (17.6-53.3) 191.000 0.638c WBC (×109/L) 6.9 (1.5-27.9) 3.2 (1.4-19.7) 8.1 (2.0-33.8) 175.000 0.374c RBC (×1012/L) 2.5±0.8 2.9±0.7 2.1±0.6 3.977 <0.001 HGB (g/L) 80.7±21.1 91.7±20.4 71.1±17.0 3.515 0.001b PLT (×109/L) 32.0 (17.0-59.5) 33.0 (20.0-62.0) 30.0 (14.5-49.3) 179.500 0.440c Proportion of bone marrow
blast cells62.4% (36.5%-83.8%) 78.2% (39.0%-87.8%) 53.7% (37.4%-82.7%) 161.500 0.214c Proportion of peripheral
blood original cells27.0% (8.5%-75.0%) 28.0% (7.0%-88.0%) 24.5% (8.8%-61.8%) 189.000 0.601c LDH(U/L) 286.0 (203.0-662.0) 286.0 (201.0-613.0) 288.5 (198.8-832.0) 204.500 0.906c Chromosomal prognostic
stratification (n)2.213 0.331a Well 14 (34.1%) 8 (42.1%) 6 (27.3%) Medium 19 (46.3%) 9 (47.4%) 10 (45.5%) Poor 8 (19.5%) 2 (10.5%) 6 (27.3%) PML-RARa positive (yes/no, n) 10 (24.4%) 8 (42.1%)/11 (57.9%) 2 (9.1%)/20 (90.9%) 4.368 0.037a MLL gene fracture
rearrangement (yes/no, n)5 (12.2%) 2 (10.5%)/17 (89.5%) 3 (13.6%)/19 (86.4%) 0.000 >0.999a AML-ETO positive (yes/no, n) 3 (7.3%) 0 (0.0%)/19 (100.0%) 3 (13.6%)/19 (86.4%) 1.146 0.284a Notes: a: Chi-square test; b: Student’s t test; c: nonparametric rank sum test; WBC: white blood cell; RBC: red blood corpuscle; HGB: hemoglobin; PLT: platelets; LDH: lactate dehydrogenase; PML-RARa: promyelocytic leukemia-retinoic acid receptor alpha; MLL: mixed lineage leukemia; AML-ETO: acute myelogenous leukemia-ETO.
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表 3 LMCV组和HMCV组患者免疫表型及FAB分型比较
Table 3 Comparison of immunophenotype and FAB typing between LMCV group and HMCV group
Contrast index (yes/no, n) Proportion LMCV group (n=19) HMCV group (n=22) Statistical value P CD2 positive 6 (14.6%) 2 (10.5%)/17 (89.5%) 4 (18.2%)/18 (81.8%) 0.062 0.804 CD7 positive 10 (24.4%) 1 (5.3%)/18 (94.7%) 9 (40.9%)/13 (59.1%) 5.225 0.022 CD19 positive 4 (9.8%) 1 (5.3%)/18 (94.7%) 3 (13.6%)/19 (86.4%) 0.139 0.409 CD56 positive 9 (22.0%) 1 (5.3%)/18 (94.7%) 8 (36.4%)/14 (63.6%) 4.048 0.043 CD10 positive 1 (2.4%) 0 (0.0%)/19 (100.0%) 1 (4.5%)/21 (95.5%) 0.000 >0.999 CD4 positive 6 (14.6%) 2 (10.5%)/17 (89.5%) 4 (18.2%)/18 (81.8%) 0.062 0.804 CD25 positive 4 (9.8%) 2 (10.5%)/17 (89.5%) 2 (9.1%)/20 (90.9%) 0.000 >0.999 M2a 1 (2.4%) 0 (0.0%)/19 (100.0%) 1 (4.5%)/21 (95.5%) 0.000 >0.999 M2b 2 (4.9%) 0 (0.0%)/19 (100.0%) 2 (9.1%)/20 (90.9%) 0.385 0.525 APL 10 (24.4%) 8 (42.1%)/11 (57.9%) 2 (9.1%)/20 (90.9%) 4.368 0.037 M4 11 (26.8%) 6 (31.6%)/13 (68.4%) 5 (22.7%)/17 (77.3%) 0.407 0.524 M5 16 (39.0%) 5 (26.3%)/14 (73.7%) 11 (50.0%)/11 (50.0%) 2.403 0.121
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表 4 影响t-AML患者预后的单因素分析
Table 4 Analysis of single factors affecting the prognosis of patients with t-AML
Influence factor OS RFS n χ2 P n χ2 P WBC (<6.9/≥6.9, ×109/L) - - - 11/13 5.019 0.025 RBC (<2.3/≥2.3, ×109/L) 16/20 7.716 0.005 11/13 13.312 <0.001 HGB (<77.0/≥77.0, g/L) 17/19 6.858 0.009 12/12 13.513 <0.001 MCV (<98.9/≥98.9, fl) 16/20 4.931 0.026 11/13 8.700 0.003 PLT (<32.0/≥32.0, ×109/L) - - - 10/14 3.100 0.078 Bone marrow blast cells (<62.4%/≥62.4%) 17/19 6.570 0.010 10/14 5.151 0.023 Well chromosomal prognostic stratification (yes/no, n) 14/22 6.816 0.009 12/12 5.694 0.017 PML-RARa positive (yes/no, n) 10/26 7.836 0.005 9/15 7.562 0.006 MLL gene fracture rearrangement (yes/no, n) - - - 2/22 4.448 0.035 CR (yes/no, n) 19/17 24.068 <0.001 19/5 11.826 0.001 Primary tumor being lymphoma 11/25 4.664 0.031 5/19 6.324 0.012 Primary tumor being malignant tumor of digestive system 3/33 19.727 <0.001 1/23 5.000 0.025 Antimetabolite 3/33 3.081 0.079 - - - CD56 positive (yes/no, n) 8/18 5.561 0.018 4/20 6.243 0.012 CD4 positive (yes/no, n) - - - 3/21 6.073 0.014 APL positive (yes/no, n) 10/26 7.836 0.005 9/15 7.562 0.006 M4 positive (yes/no, n) 7/29 3.049 0.081 - - - M5 positive (yes/no, n) 15/21 2.994 0.084 9/15 8.970 0.003 CBL mutation positive (yes/no, n) 1/35 6.200 0.013 1/23 5.000 0.025 Notes: -: no statistics have been calculated as all cases have been excluded; MCV: mean corpuscular volume; CR: complete remission; CBL: casitas B-lineage lymphoma.
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