Internal Medicine and Pediatrics.
Department of Medicine, Section of Hematology/Oncology, and.
Blood Adv. 2022 Sep 13;6(17):5146-5151. doi: 10.1182/bloodadvances.2022007699.
Patients with acute lymphoblastic leukemia (ALL) are at increased risk of thrombotic and/or bleeding events during early chemotherapy, especially when receiving asparaginase. D-dimer is a marker of fibrinolysis that has been associated with thrombotic risk in solid cancers and acute myeloid leukemia; however, to date, no ALL-based study has assessed D-dimer level and risk for thrombosis. We sought to examine D-dimer as a biomarker for risk of thrombosis or bleeding during ALL treatment in a retrospective cohort study at The University of Chicago. We identified 61 consecutive adult patients with ALL, gathering demographic characteristics, treatment regimens, initial biomarkers including D-dimer, and assessing occurrence of venous or arterial thrombosis and bleeding in the first 100 days after diagnosis (index). The 100-day cumulative incidence (95% confidence interval [CI]) of venous or arterial thrombosis in patients with high D-dimer (≥4 µg/mL) was 52.9% (95% CI, 26.4-73.8) compared with 13.8% (95% CI, 5.5-25.7) in patients with low to moderate D-dimer (<4 µg/mL), corresponding with a hazard ratio of 5.04 (95% CI, 1.79-14.22). When testing for potential confounders in a series of bivariate logistic regression models, the association between D-dimer and thrombosis remained after adjusting for body mass index, age, sex, asparaginase treatment, disseminated intravascular coagulation score, initial platelet level, and ALL phenotype. In conclusion, D-dimer levels at ALL diagnosis are associated with venous or arterial thrombosis at 100 days. Future studies should include D-dimer collated with other known risk factors to build a risk assessment model for thrombosis in patients with newly diagnosed ALL.
急性淋巴细胞白血病 (ALL) 患者在早期化疗期间发生血栓形成和/或出血事件的风险增加,尤其是在接受门冬酰胺酶治疗时。D-二聚体是纤维蛋白溶解的标志物,与实体瘤和急性髓系白血病的血栓形成风险相关;然而,迄今为止,尚无基于 ALL 的研究评估 D-二聚体水平与血栓形成风险的关系。我们试图在芝加哥大学的一项回顾性队列研究中,检查 D-二聚体作为 ALL 治疗期间血栓形成或出血风险的生物标志物。我们确定了 61 例连续的成人 ALL 患者,收集了人口统计学特征、治疗方案、初始生物标志物,包括 D-二聚体,并评估了诊断后 100 天内静脉或动脉血栓形成和出血的发生情况(索引)。D-二聚体水平较高(≥4 µg/mL)的患者在 100 天内发生静脉或动脉血栓形成的累积发生率(95%置信区间[CI])为 52.9%(95%CI,26.4-73.8),而 D-二聚体水平较低至中度(<4 µg/mL)的患者为 13.8%(95%CI,5.5-25.7),相应的风险比为 5.04(95%CI,1.79-14.22)。在一系列二变量逻辑回归模型中进行潜在混杂因素检验时,在调整了体重指数、年龄、性别、门冬酰胺酶治疗、弥散性血管内凝血评分、初始血小板计数和 ALL 表型后,D-二聚体与血栓形成之间的关联仍然存在。总之,ALL 诊断时的 D-二聚体水平与 100 天时的静脉或动脉血栓形成相关。未来的研究应包括 D-二聚体与其他已知危险因素相结合,以建立新诊断为 ALL 的患者的血栓形成风险评估模型。