New Progression in Influencing Factors and Risk Prediction Models for Lymphoma-associated Venous Thromboembolism

doi:10.12114/j.issn.1007-9572.2021.00.600

Abstract

Abstract: Venous thromboembolism（VTE）is a common complication，and the second leading non-cancer cause of death in cancer patients. Lymphoma is a type of cancer with a high incidence of VTE. However，there is no consensus on the risk factors and prevention methods for lymphoma-associated VTE. To provide the latest guidance on the prevention and treatment of lymphoma-associated VTE，in reviewing the recent guidelines and literature，we overviewed the influencing factors of lymphoma-associated VTE，including types and treatment of lymphoma，clinical laboratory indicators and anti-tumor therapies. Besides that，we also summarized and analyzed the recently developed risk prediction models for lymphoma-associated VTE，including the Khorana Risk Score，Ottawa Score，Michigan Risk Score and ThroLy Lymphoma Score.

Key words: Lymphoma, Venous thromboembolism, Influence factors, Prognostic model, Review

摘要： 静脉血栓（VTE）是恶性肿瘤的常见并发症，亦是导致肿瘤患者死亡的第二位非肿瘤致死因素。淋巴瘤是VTE发病率较高的肿瘤之一，然而，目前针对淋巴瘤相关VTE风险的危险因素以及防治方法尚未达到一致共识。因此，本文将结合最新指南及文献总结，将淋巴瘤相关VTE的影响因素及预测模型作一综述，分别介绍与淋巴瘤疾病本身、临床检验指标以及抗肿瘤治疗相关的VTE危险因素。同时，将4种VTE预测模型（即：Khorana评分、Ottawa评分、Michigan评分以及ThroLy评分）对淋巴瘤VTE风险的预测价值进行分析，为淋巴瘤相关VTE的防治提供新的指导。

关键词: 淋巴瘤, 静脉血栓, 影响因素, 预后模型, 综述

YANG Jingshi,ZOU Liqun. New Progression in Influencing Factors and Risk Prediction Models for Lymphoma-associated Venous Thromboembolism　[J]. Chinese General Practice, 2021, 24(23): 2992-2997. DOI: 10.12114/j.issn.1007-9572.2021.00.600.
杨婧诗,邹立群. 淋巴瘤相关静脉血栓的影响因素及风险评估模型的研究进展[J]. 中国全科医学, 2021, 24(23): 2992-2997. DOI: 10.12114/j.issn.1007-9572.2021.00.600.

References

［1］TIMP J F，BRAEKKAN S K，VERSTEEG H H，et al. Epidemiology of cancer-associated venous thrombosis［J］. Blood，2013，122（10）：1712-1723. DOI：10.1182/blood-2013-04-460121.
［2］KHORANA A A，KUDERER N M，CULAKOVA E，et al. Development and validation of a predictive model for chemotherapy-associated thrombosis［J］. Blood，2008，111（10）：4902-4907. DOI：10.1182/blood-2007-10-116327.
［3］ANTIC D，MILIC N，NIKOLOVSKI S，et al. Development and validation of multivariable predictive model for thromboembolic events in lymphoma patients［J］. Am J Hematol，2016，91（10）：1014-1019. DOI：10.1002/ajh.24466.
［4］YOKOYAMA K. Thrombosis in lymphoma patients and in myeloma patients［J］. Keio J Med，2015，64（3）：37-43. DOI：10.2302/kjm.2014-0017-RE.
［5］KEKRE N，CONNORS J M. Venous thromboembolism incidence in hematologic malignancies［J］. Blood Rev，2019，33：24-32. DOI：10.1016/j.blre.2018.06.002.
［6］GOLDSCHMIDT N，LINETSKY E，SHALOM E，et al. High incidence of thromboembolism in patients with central nervous system lymphoma［J］. Cancer，2003，98（6）：1239-1242. DOI：10.1002/cncr.11623.
［7］BYUN J M，HONG J，YOON S S，et al. Incidence and characteristics of venous thromboembolism in Asian patients with primary central nervous system lymphoma undergoing chemotherapy［J］. Thromb Res，2019，183：131-135. DOI：10.1016/j.thromres.2019.10.002.
［8］ZHOU X，TEEGALA S，HUEN A，et al. Incidence and risk factors of venous thromboembolic events in lymphoma［J］. Am J Med，2010，123（10）：935-941. DOI：10.1016/j.amjmed.2010.05.021.
［9］FARGE D，BOUNAMEAUX H，BRENNER B，et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer［J］. Lancet Oncol，2016，17（10）：e452-466. DOI：10.1016/S1470-2045（16）30369-2.
［10］AY C，VORMITTAG R，DUNKLER D，et al. D-dimer and prothrombin fragment 1+2 predict venous thromboembolism in patients with cancer：results from the Vienna Cancer and Thrombosis Study［J］. J Clin Oncol，2009，27（25）：4124-4129. DOI：10.1200/JCO.2008.21.7752.
［11］LEKOVIC D，MILJIC P，MIHALJEVIC B. Increased risk of venous thromboembolism in patients with primary mediastinal large B-cell lymphoma［J］. Thromb Res，2010，126（6）：477-480. DOI：10.1016/j.thromres.2010.08.017.
［12］SAMUELSON BANNOW B T，KONKLE B A. Laboratory biomarkers for venous thromboembolism risk in patients with hematologic malignancies：a review［J］. Thromb Res，2018，163：138-145. DOI：10.1016/j.thromres.2018.01.037.
［13］NEGAARD H F S，IVERSEN P O，?STENSTAD B，et al. Hypercoagulability in patients with haematological neoplasia：no apparent initiation by tissue factor［J］. Thromb Haemost，2008，99（6）：1040-1048. DOI：10.1160/TH07-09-0541.
［14］RUPA-MATYSEK J，GIL L，BARANSKA M，et al. Mean platelet volume as a predictive marker for venous thromboembolism in patients treated for Hodgkin lymphoma［J］. Oncotarget，2018，9（30）：21190-21200. DOI：10.18632/oncotarget.25002.
［15］RUPA-MATYSEK J，GIL L，KROLL-BALCERZAK R，et al. Mean platelet volume as a predictive marker for venous thromboembolism and mortality in patients treated for diffuse large B-cell lymphoma［J］. Hematol Oncol，2017，35（4）：456-464. DOI：10.1002/hon.2321.
［16］RIEDL J，KAIDER A，REITTER E M，et al. Association of mean platelet volume with risk of venous thromboembolism and mortality in patients with cancer. Results from the Vienna Cancer and Thrombosis Study（CATS）［J］. Thromb Haemost，2014，111（4）：670-678. DOI：10.1160/TH13-07-0603.
［17］YILDIZ A，ALBAYRAK M，PALA ?，et al. The incidence and risk factors of thrombosis and the need for thromboprophylaxis in lymphoma and leukemia patients：a 9-year single-center experience ［J］. J Oncol Pharm Pract，2020，26（2）：386-396. DOI：10.1177/1078155219851540.
［18］LI J S，TIAN X D，WANG M J，et al. A primary retroperitoneal anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor thrombosis［J］. Onco Targets Ther，2018，11：9007-9011. DOI：10.2147/OTT.S183298.
［19］PARK H，KIM J W，YOUK J，et al. Serum free light chain difference and β2 microglobulin levels are risk factors for thromboembolic events in patients with AL amyloidosis［J］. Clin Lymphoma Myeloma Leuk，2018，18（6）：408-414. DOI：10.1016/j.clml.2018.03.005.
［20］RUPA-MATYSEK J，GIL L，KAZMIERCZAK M，et al. Prediction of venous thromboembolism in newly diagnosed patients treated for lymphoid malignancies：validation of the Khorana Risk Score［J］. Med Oncol，2017，35（1）：5. DOI：10.1007/s12032-017-1065-4.
［21］JACCARD A，GACHARD N，MARIN B，et al. Efficacy of L-asparaginase with methotrexate and dexamethasone（AspaMetDex regimen）in patients with refractory or relapsing extranodal NK/T-cell lymphoma，a phase 2 study［J］. Blood，2011，117（6）：1834-1839. DOI：10.1182/blood-2010-09-307454.
［22］DE STEFANO V，ZA T，CIMINELLO A，et al. Haemostatic alterations induced by treatment with asparaginases and clinical consequences［J］. Thromb Haemost，2015，113（2）：247-261. DOI：10.1160/TH14-04-0372.
［23］LEE J H，LEE J，YHIM H Y，et al. Venous thromboembolism following L-asparaginase treatment for lymphoid malignancies in Korea［J］. J Thromb Haemost，2017，15（4）：655-661. DOI：10.1111/jth.13636.
［24］SANFILIPPO K M，WANG T F，GAGE B F，et al. Incidence of venous thromboembolism in patients with non-Hodgkin lymphoma［J］. Thromb Res，2016，143：86-90. DOI：10.1016/j.thromres.2016.05.008.
［25］ZANGARI M，SIEGEL E，BARLOGIE B，et al. Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide：implications for therapy［J］. Blood，2002，100（4）：1168-1171. DOI：10.1182/blood-2002-01-0335.
［26］PAREDES N，XU L，BERRY L R，et al. The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces［J］. Br J Haematol，2003，120（2）：315-324. DOI：10.1046/j.1365-2141.2003.03971.x.
［27］DAVID R J，BARAN A，LOH K P，et al. Complications associated with dose-adjusted EPOCH-rituximab therapy for non-Hodgkin lymphoma［J］. Clin Lymphoma Myeloma Leuk，2018，18（12）：781-787. DOI：10.1016/j.clml.2018.08.014.
［28］ARORA M，GOWDA S，TUSCANO J. A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma［J］. Ther Adv Hematol，2016，7（4）：209-221. DOI：10.1177/2040620716652861.
［29］NOWAKOWSKI G S，LAPLANT B，MACON W R，et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma：a phase Ⅱstudy［J］. J Clin Oncol，2015，33（3）：251-257. DOI：10.1200/JCO.2014.55.5714.
［30］ALBERTSSON-LINDBLAD A，KOLSTAD A，LAURELL A，et al.
Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma［J］. Blood，2016，128（14）：1814-1820. DOI：10.1182/blood-2016-03-704023.
［31］NOWAKOWSKI G S，LAPLANT B，HABERMANN T M，et al. Lenalidomide can be safely combined with R-CHOP（R2CHOP）in the initial chemotherapy for aggressive B-cell lymphomas：phase I study［J］. Leukemia，2011，25（12）：1877-1881. DOI：10.1038/leu.2011.165.
［32］PAL R，MONAGHAN S A，HASSETT A C，et al. Immunomodulatory derivatives induce PU. 1 down-regulation，myeloid maturation arrest，and neutropenia［J］. Blood，2010，115（3）：605-614. DOI：10.1182/blood-2009-05-221077.
［33］YAMSHON S，CHRISTOS P J，DEMETRES M，et al. Venous thromboembolism in patients with B-cell non-hodgkin lymphoma treated with lenalidomide：a systematic review and meta-analysis［J］. Blood Adv，2018，2（12）：1429-1438. DOI：10.1182/bloodadvances.2018016683.
［34］KEY N S，KHORANA A A，KUDERER N M，et al. Venous thromboembolism prophylaxis and treatment in patients with cancer：ASCO clinical practice guideline update［J］. J Clin Oncol，2020，38（5）：496-520. DOI：10.1200/JCO.19.01461.
［35］SANTI RM，CECCARELLI M，BERNOCCO E，et al. Khorana score and histotype predicts incidence of early venous thromboembolism in non-Hodgkin lymphomas. A pooled-data analysis of 12 clinical trials of Fondazione Italiana Linfomi（FIL）［J］. Thromb Haemost，2017，10.1160/TH16-11-0895. DOI：10.1160/TH16-11-0895.
［36］HOHAUS S，TISI M C，BARTOLOMEI F，et al. Risk factors for venous thromboembolism in patients with lymphoma requiring hospitalization［J］. Blood Cancer J，2018，8（6）：54. DOI：10.1038/s41408-018-0096-1.
［37］LOUZADA M L，CARRIER M，LAZO-LANGNER A，et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism［J］. Circulation，2012，126（4）：448-454. DOI：10.1161/CIRCULATIONAHA.111.051920.
［38］DEN EXTER P L，KOOIMAN J，HUISMAN M V. Validation of the Ottawa prognostic score for the prediction of recurrent venous thromboembolism in patients with cancer-associated thrombosis［J］. J Thromb Haemost，2013，11（5）：998-1000. DOI：10.1111/jth.12192.
［39］ALATRI A，MAZZOLAI L，FONT C，et al. Low discriminating power of the modified Ottawa VTE risk score in a cohort of patients with cancer from the RIETE registry［J］. Thromb Haemost，2017，117（8）：1630-1636. DOI：10.1160/TH17-02-0116.
［40］CHOPRA V，KAATZ S，CONLON A，et al. The Michigan Risk Score to predict peripherally inserted central catheter-associated thrombosis［J］. J Thromb Haemost，2017，15（10）：1951-1962. DOI：10.1111/jth.13794.
［41］LUND J L，?STG?RD L S，PRANDONI P，et al. Incidence，determinants and the transient impact of cancer treatments on venous thromboembolism risk among lymphoma patients in Denmark［J］. Thromb Res，2015，136（5）：917-923. DOI：10.1016/j.thromres.2015.09.001.
［42］JASTI N，STREIFF M B. Prevention and treatment of thrombosis associated with central venous catheters in cancer patients［J］. Expert Rev Hematol，2014，7（5）：599-616. DOI：10.1586/17474086.2014.954541.
［43］RUPA-MATYSEK J，BRZEZNIAKIEWICZ-JANUS K，GIL L，et al. Evaluation of the ThroLy score for the prediction of venous thromboembolism in newly diagnosed patients treated for lymphoid malignancies in clinical practice ［J］. Cancer Med，2018，7（7）：2868-2875. DOI：10.1002/cam4.1540.
［44］KHORANA A A，FRANCIS C W，CULAKOVA E，et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy ［J］. J Thromb Haemost，2007，5（3）：632–634. DOI：10.1111/j.1538-7836.2007.02374.x.
［45］MAHAJAN A，BRUNSON A，WHITE R，et al. The epidemiology of cancer-associated venous thromboembolism：an update［J］. Semin Thromb Hemost，2019，45（4）：321-325. DOI：10.1055/s-0039-1688494.

[1]	WANG Xu, WEI Xu, ZHU Liguo, FENG Tianxiao, WANG Zhipeng, SHI Bin. Research Ideas of the Efficacy Mechanism and Prospect Analysis of Traditional Chinese Manipulative Therapy on Treating Spinal Degenerative Diseases with Combination of Medicine and Industry [J]. Chinese General Practice, 2023, 26(33): 4118-4124.
[2]	XIN Gongkai, CONG Xin, YUAN Lei, CHENG Yuetong, NI Cuiping, ZHANG Weiwei, ZHANG Pingping, LIU Yu. Research Progress on Comprehensive Assessment Tools for the Elderly with Dementia [J]. Chinese General Practice, 2023, 26(33): 4103-4109.
[3]	ZHANG Siyu, ZHOU Yuqiu, DU Xiaohui, WANG Zhengjun. Advances in Duration of Untreated Psychosis and Its Early Intervention [J]. Chinese General Practice, 2023, 26(33): 4110-4117.
[4]	MENG Jiangtao, YANG Siyu, SUN Lei, LEI Ruining, ZHAO Xiaoxia. Advances in the Prognostic Value of Diffusion Tensor Imaging with Motor Evoked Potential for Motor Function in Cerebral Infarction Patients with Hemiplegia [J]. Chinese General Practice, 2023, 26(32): 4098-4102.
[5]	WANG Jiaxin, ZHAO Yali. Domestic and International Assessment Tools for Medical Teamwork: a Systematic Review [J]. Chinese General Practice, 2023, 26(31): 3951-3962.
[6]	WEI Mengyu, WANG Jiajia, ZHANG Yingying, LI Chunyang, LI Jiansheng. Research Status of Patient-reported Outcome Assessment Tools for Obstructive Sleep Apnea [J]. Chinese General Practice, 2023, 26(30): 3725-3733.
[7]	YUAN Xiwei, NAN Yuemin. Research Progress of Structure, Function and Mechanism of Action of Mitofusin 2 in Liver Diseases [J]. Chinese General Practice, 2023, 26(30): 3841-3846.
[8]	XIAO Yuqian, BAI Yanjie, WANG Yan, CHEN Shuying, CHEN Limin, SUN Kexin, WAN Jun. Research Progress of Mitochondrial Transfer in Post-stroke Cognitive Impairment [J]. Chinese General Practice, 2023, 26(30): 3833-3840.
[9]	LIU Yu, YUE Ting, YANG Dongyu, ZHAO Zhongting, YANG Jibo, ZHU Tiantian. Research Progress on Mechanism of Autophagy in the Pathogenesis of Rheumatoid Arthritis [J]. Chinese General Practice, 2023, 26(29): 3710-3714.
[10]	PU Yu, ZHANG Jixiang, DONG Weiguo. Advances in Ferroptosis and Inflammatory Bowel Disease [J]. Chinese General Practice, 2023, 26(29): 3698-3703.
[11]	REN Yanfeng, LIU Shimeng, TAO Ying, CHEN Yingyao. A Systematic Review of Medication Preferences for Patients with Depression Based on Discrete Choice Experiment and Best-worst Scaling [J]. Chinese General Practice, 2023, 26(28): 3559-3564.
[12]	TANG Shilan, XIE Kexin, LIU Lingyu, QI Tiantian, YANG Yansui. Advances in Rehabilitation Outcomes and Care in Patients with Prolonged Disorders of Consciousness [J]. Chinese General Practice, 2023, 26(27): 3342-3348.
[13]	LIANG Xuemei, WANG Rui, ZHAO Yuhuan, XU Tianjiao, WANG Wei, SUN Weidong. Transcranial Low-level Laser Therapy: a Novel Treatment for Depression [J]. Chinese General Practice, 2023, 26(27): 3335-3341.
[14]	CHEN Xiaofen, CHEN Yuhan, MA Juan. Recent Strides in Novel Treatments for Inflammatory Bowel Disease [J]. Chinese General Practice, 2023, 26(27): 3349-3354.
[15]	ZHU Guangyu, CHENG Yuxin, LU Xuejing. Research Progress of Ocular Glymphatic System and Related Ocular Diseases [J]. Chinese General Practice, 2023, 26(26): 3330-3334.