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伴有血栓事件的急性早幼粒细胞白血病患者的生化危险因素和结局:配对分析。

Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis.

机构信息

Department of Emergency, Peking University People's Hospital, Beijing, 100044, China.

Department of Hematology, Peking University People's Hospital, Beijing, 100044, China.

出版信息

J Thromb Thrombolysis. 2024 Jun;57(5):828-841. doi: 10.1007/s11239-024-02988-x. Epub 2024 May 3.

Abstract

Acute promyelocytic leukemia (APL) stands out as a distinctive form of acute leukemia, exhibiting a higher occurrence of thrombotic events when contrasted with other leukemia subtypes. Since thrombosis is a relatively rare but unfavorable condition with poor prognostic implications, it is crucial to determine the risk factors for thrombotic events in APL(thrombosis in large venous or arterial from onset to differentiation therapy in 30d). We performed a retrospective study involving 950 APL patients between January 2000 and October 2022, from which 123 were excluded by younger than 16 years of age, 95 were excluded by incomplete data, and 6 were excluded by thrombosis related to CVC or PICC. A total of 23 APL patients with thrombosis for inclusion in our analysis were performed a 1:5 ratio matching based on sex (perfect match) and age (within 5 years) to patients without thrombosis. These patients were continuously monitored in the outpatient department over a period of 5 years. We meticulously examined clinical and laboratory data to pinpoint the risk factors related to thrombotic events in APL. Our primary clinical endpoints were all-cause mortality and achieving complete remission, while secondary clinical outcomes included APL relapse. Thrombotic events were observed in 2.4% (23/950) of APL patients. Compared to patients without thrombosis, patients with thrombosis had higher lactate dehydrogenase (LDH) [313 (223, 486) vs. 233 (188, 367) U/L, p = 0.020], higher indirect bilirubin [11.2 (7.4, 18.6) vs.8.3 (6.0, 10.7) umol/L, p = 0.004], higher creatinine [72 (62, 85) vs. 63 (54, 74) umol/L, p = 0.026], higher CD2 expression (65.2 vs. 15.2%, p < 0.001), higher CD15 expression (60.9 vs. 24.3%, p = 0.001), and PML/RARαisoforms (p < 0.001). Multivariate-logistic-regression analysis revealed several factors that were markedly related to thrombosis, including LDH (OR≈1.003, CIs≈1.000-1.006, p = 0.021), indirect bilirubin (OR≈1.084, CIs≈1.000-1.188, p = 0.043), CD2 expression positive (OR≈16.629, CIs≈4.001-62.832, p < 0.001), and CD15 expression positive (OR≈7.747, CIs≈2.005-29.941, p = 0.003). The S-type (OR≈0.012, CIs≈0.000-0.310, p = 0.008) and L-type (OR≈0.033, CIs≈0.002-0.609, p = 0.022) PML/RARα isoforms were negatively associated with thrombosis. Kaplan-Meier curves indicated that the survival rates were remarkably varied between APL patients with and without thrombosis (HR:21.34, p < 0.001). LDH and indirect bilirubin are variables significantly associated with thrombosis in APL, S-type and L-type PML/RARαisoforms exhibit a negative association with thrombotic events. The thrombotic events of APL can predict the subsequent survival of thrombosis. The findings of our study have the potential to facilitate early detection of thrombosis and enhance the prognosis for individuals with APL who develop thrombosis. Further validation of our findings will be essential through future prospective or multicenter studies.

摘要

急性早幼粒细胞白血病(APL)是一种独特的急性白血病形式,与其他白血病亚型相比,其血栓事件的发生率更高。由于血栓形成是一种相对罕见但不利的情况,预后不良,因此确定 APL 中血栓形成的危险因素(30 天内从发病到分化治疗的大静脉或动脉血栓形成)至关重要。我们进行了一项回顾性研究,纳入了 2000 年 1 月至 2022 年 10 月期间的 950 例 APL 患者,其中 123 例因年龄小于 16 岁而被排除,95 例因数据不完整而被排除,6 例因与 CVC 或 PICC 相关的血栓而被排除。共有 23 例 APL 患者发生血栓形成,我们根据性别(完全匹配)和年龄(5 年内)与无血栓形成的患者进行了 1:5 的比例匹配。这些患者在门诊接受了 5 年的连续监测。我们仔细检查了临床和实验室数据,以确定与 APL 血栓形成相关的危险因素。我们的主要临床终点是全因死亡率和完全缓解,次要临床结果包括 APL 复发。在 950 例 APL 患者中,有 2.4%(23/950)发生血栓形成。与无血栓形成的患者相比,有血栓形成的患者乳酸脱氢酶(LDH)更高[313(223,486)vs.233(188,367)U/L,p=0.020],间接胆红素更高[11.2(7.4,18.6)vs.8.3(6.0,10.7)μmol/L,p=0.004],肌酐更高[72(62,85)vs.63(54,74)μmol/L,p=0.026],CD2 表达更高[65.2% vs.15.2%,p<0.001],CD15 表达更高[60.9% vs.24.3%,p=0.001],PML/RARα 异构体更多[p<0.001]。多变量逻辑回归分析显示,有几个因素与血栓形成明显相关,包括 LDH(OR≈1.003,CIs≈1.000-1.006,p=0.021)、间接胆红素(OR≈1.084,CIs≈1.000-1.188,p=0.043)、CD2 表达阳性(OR≈16.629,CIs≈4.001-62.832,p<0.001)和 CD15 表达阳性(OR≈7.747,CIs≈2.005-29.941,p=0.003)。S 型(OR≈0.012,CIs≈0.000-0.310,p=0.008)和 L 型(OR≈0.033,CIs≈0.002-0.609,p=0.022)PML/RARα 异构体与血栓形成呈负相关。Kaplan-Meier 曲线表明,有血栓形成和无血栓形成的 APL 患者的生存率差异显著(HR:21.34,p<0.001)。LDH 和间接胆红素是与 APL 血栓形成显著相关的变量,S 型和 L 型 PML/RARα 异构体与血栓形成事件呈负相关。APL 的血栓形成事件可以预测随后的血栓形成患者的生存情况。我们的研究结果有可能早期发现血栓形成,并改善发生血栓形成的 APL 患者的预后。未来需要通过前瞻性或多中心研究进一步验证我们的发现。

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