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含聚乙二醇化大肠埃希菌 asparaginase 方案与不含该方案治疗成人急性淋巴细胞白血病的静脉血栓栓塞发生率及危险因素。

Venous thromboembolism incidence and risk factors in adults with acute lymphoblastic leukemia treated with and without pegylated E. coli asparaginase-containing regimens.

机构信息

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

出版信息

Cancer Chemother Pharmacol. 2021 Jun;87(6):817-826. doi: 10.1007/s00280-021-04252-y. Epub 2021 Mar 7.

Abstract

PURPOSE

Asparaginases, key agents in treatment of acute lymphoblastic leukemia (ALL), are associated with venous thromboembolism (VTE). While risks of short-acting asparaginase-related VTE is well-known, we studied VTE incidence and risk factors in adult ALL patients treated with and without long-acting pegylated asparaginase (PegA).

METHODS

Single-center, retrospective analysis of 89 ALL patients treated with (n = 61) or without (n = 28) PegA at Greenebaum Comprehensive Cancer Center. Reviewed patient and disease characteristics, treatment, and VTE incidence.

RESULTS

VTE during treatment occurred in 31 patients (35%), and was associated with PegA (p = 0.001) and Philadelphia chromosome negativity (p = 0.002). Among PegA recipients, VTE was associated with a significantly higher mean body mass index (BMI) of 31.3 kg/m (p = 0.037), and was more common with pre-T/T cell compared to pre-B/B cell ALL (68.2% vs. 33.3%, p = 0.009). Antithrombin-III (ATIII) levels were measured for 26 patients; 16 (61.5%) were < 50%. Of those, 8 (50%) experienced VTE, while 3 of 10 (30%) patients with ATIII levels ≥ 50% experienced VTE. VTE occurred in 7 of 13 (54%) of patients who received ATIII repletion. There was a trend toward a higher incidence of VTE in the PegA group among patients with non-O compared to O blood type (55.9% vs. 33.3%, p = 0.079) as well as those with a higher hemoglobin at diagnosis (9.3 vs 8.1 g/dL, p = 0.056).

CONCLUSION

This study confirms PegA as a risk factor for VTE in patients with ALL. Risk factors among those receiving PegA include higher BMI and pre-T/T cell ALL. ATIII repletion was not shown to be protective against VTE. There was a higher incidence of VTE in patients who received PegA with non-O compared to O blood type, but the precise correlation is uncertain.

摘要

目的

天冬酰胺酶是治疗急性淋巴细胞白血病(ALL)的关键药物,与静脉血栓栓塞症(VTE)有关。虽然短期作用的天冬酰胺酶相关 VTE 的风险众所周知,但我们研究了在使用和不使用长效聚乙二醇化天冬酰胺酶(PegA)治疗的成人 ALL 患者中的 VTE 发生率和危险因素。

方法

对 Greenebaum 综合癌症中心 89 例 ALL 患者进行了单中心回顾性分析,其中接受(n=61)或未接受(n=28)PegA 治疗。回顾患者和疾病特征、治疗和 VTE 发生率。

结果

治疗期间发生 VTE 的患者有 31 例(35%),与 PegA(p=0.001)和费城染色体阴性(p=0.002)有关。在接受 PegA 治疗的患者中,VTE 与更高的平均体重指数(BMI)31.3kg/m(p=0.037)相关,且前 T/T 细胞型 ALL 比前 B/B 细胞型 ALL 更常见(68.2%比 33.3%,p=0.009)。对 26 例患者进行了抗凝血酶-III(ATIII)水平检测;其中 16 例(61.5%)<50%。其中,8 例(50%)发生 VTE,而 ATIII 水平≥50%的 10 例患者中有 3 例发生 VTE。在接受 ATIII 补充的 13 例患者中,有 7 例发生 VTE。在非 O 型血与 O 型血相比,PegA 组患者的 VTE 发生率更高(55.9%比 33.3%,p=0.079),以及诊断时血红蛋白更高的患者(9.3 比 8.1g/dL,p=0.056)。

结论

本研究证实 PegA 是 ALL 患者 VTE 的危险因素。接受 PegA 治疗的患者的危险因素包括更高的 BMI 和前 T/T 细胞 ALL。ATIII 补充并未显示出对 VTE 的保护作用。与 O 型血相比,接受 PegA 治疗的非 O 型血患者的 VTE 发生率更高,但确切的相关性尚不确定。

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