Venous thromboembolism in adolescents and young adults with acute lymphoblastic leukemia treated on a pediatric-inspired regimen

IF 12.9 1区 医学 Q1 HEMATOLOGY
Shai Shimony, Hari S. Raman, Yael Flamand, Julia Keating, Jonathan D. Paolino, Yannis K. Valtis, Andrew E. Place, Lewis B. Silverman, Stephen E. Sallan, Lynda M. Vrooman, Andrew M. Brunner, Donna S. Neuberg, Ilene Galinsky, Jacqueline S. Garcia, Eric S. Winer, Martha Wadleigh, Richard M. Stone, Jean M. Connors, Daniel J. DeAngelo, Marlise R. Luskin
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Abstract

Asparaginase (ASP)-containing regimens for acute lymphoblastic leukemia (ALL) are associated with venous thromboembolism (VTE). We evaluated the prevalence, risk factors, role of prophylaxis and clinical impact of VTE among adolescents and young adult (AYA) patients (15–50 years) treated on Dana-Farber Cancer Institute (DFCI) ALL protocols. The 1- and 2-year cumulative incidence of VTE were 31.9% (95% CI: 27.0%, 36.9%) and 33.5% (95% CI: 28.5%, 38.5%) respectively, with most events occurring during ASP-based consolidation phase (68.6%). VTE was more frequent in patients with overweight/obese vs. normal BMI (39.2% vs. 29.0%, p = 0.048). In a 1-year landmark analysis, the 4-year overall survival was 91.5%, without difference between patients with vs. without VTE (93.8% vs. 90.0%, p = 0.93). Relapse and non-relapse mortality rates were also similar. Among patients treated at Dana-Farber/Harvard Cancer Center, cerebral sinus vein thrombosis occurred in 3.6% of patients (8.5% of VTE events) in comparison to pulmonary embolism (32.9%) and deep vein thromboses (58.6%, 24.4% line-associated). In a Cox regression model for VTE free-time, elevated BMI was associated with shorter VTE free-time (HR 1.94 [95% CI 1.13-3.35], p = 0.018), while low molecular weight heparin (LMWH) prophylaxis as time-varying covariate was not. In conclusion, we found that VTE was frequent in AYAs treated on DFCI ALL protocols but did not impact survival outcomes. Overweight/obese BMI increased risk for VTE.

Abstract Image

采用儿科启发疗法治疗急性淋巴细胞白血病的青少年和年轻成人的静脉血栓栓塞症
含有天冬酰胺酶(ASP)的急性淋巴细胞白血病(ALL)治疗方案与静脉血栓栓塞(VTE)有关。我们评估了接受丹娜法伯癌症研究所(DFCI)ALL 方案治疗的青少年和年轻成人(AYA)患者(15-50 岁)中 VTE 的发病率、风险因素、预防作用和临床影响。VTE的1年和2年累计发生率分别为31.9%(95% CI:27.0%, 36.9%)和33.5%(95% CI:28.5%, 38.5%),其中大部分发生在以ASP为基础的巩固治疗阶段(68.6%)。超重/肥胖患者的 VTE 发生率高于体重指数正常者(39.2% 对 29.0%,P = 0.048)。在为期1年的标志性分析中,4年总生存率为91.5%,有VTE的患者与无VTE的患者之间没有差异(93.8% vs. 90.0%,p = 0.93)。复发和非复发死亡率也相似。在丹娜-法伯/哈佛癌症中心接受治疗的患者中,有3.6%的患者发生了脑窦静脉血栓(占VTE事件的8.5%),而肺栓塞(32.9%)和深静脉血栓(58.6%,24.4%与管路相关)则没有发生。在 VTE 自由时间的 Cox 回归模型中,BMI 升高与 VTE 自由时间缩短相关(HR 1.94 [95% CI 1.13-3.35],p = 0.018),而低分子量肝素 (LMWH) 预防作为时变协变量则不相关。总之,我们发现在接受 DFCI ALL 方案治疗的亚健康人群中,VTE 的发生率很高,但并不影响生存结果。超重/肥胖的体重指数会增加 VTE 风险。
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来源期刊
CiteScore
16.70
自引率
2.30%
发文量
153
审稿时长
>12 weeks
期刊介绍: Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as: Preclinical studies of new compounds, especially those that provide mechanistic insights Clinical trials and observations Reviews related to new drugs and current management of hematologic malignancies Novel observations related to new mutations, molecular pathways, and tumor genomics Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.
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