Oxaliplatin-Mediated Increase in Spleen Size As a Biomarker for the Development of Hepatic Sinusoidal Injury
Oxaliplatin-Mediated Increase in Spleen Size As a Biomarker for the Development of Hepatic Sinusoidal Injury
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DOI：
10.1200/jco.2009.27.5701
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发表时间：
2010-05-20
影响因子：
45.3
通讯作者：
Kopetz, Scott
中科院分区：
文献类型：
--
作者：
Overman, Michael J.;Maru, Dipen M.;Kopetz, Scott
目的奥沙利铂化疗可引起肝窦损伤，导致肝窦损伤和门静脉高压症。我们试图探索奥沙利铂诱导的肝窦损伤、脾脏大小增加和随后的血小板减少症之间的关系。患者和方法我们回顾性评估了136例接受氟尿嘧啶和奥沙利铂（FOLFOX）或氟嘧啶辅助治疗的II期或III期结直肠癌患者化疗暴露、脾脏大小变化（通过体积测量确定）和血小板计数之间的关系。对63例转移性结直肠癌患者在肝切除术前接受氟嘧啶和奥沙利铂治疗的肝窦损伤和脾脏大小的变化进行分级。结果接受FOLFOX辅助治疗的患者中，86%的患者脾脏增大（P < 0.001），其中24%的患者的>= 50%增大。使用氟嘧啶辅助治疗的患者脾脏大小没有明显增加。脾脏大小的增加与奥沙利铂累积剂量相关（P = 0.003）。脾肿大患者（>= 50%）化疗结束后第一年血小板减少率较高（27% vs 5%; P = 0.003）。在术前使用氟嘧啶和奥沙利铂治疗的肝转移患者中，脾脏大小的增加在单因素分析（P = 0.03）和多因素分析（P = 0.02）中都是较高组织学级别的窦损伤的预测因子。结论脾脏大小的增加与肝窦损伤程度的增加有关，可以作为识别肝窦毒性危险患者的简单方法。奥沙利铂引起的脾脏增大应被认为是奥沙利铂治疗后持续性血小板减少的潜在病因。
PurposeOxaliplatin-based chemotherapy can cause hepatic sinusoidal injury, with resultant sinusoidal damage and portal hypertension. We sought to explore the relationship between oxaliplatin induced hepatic sinusoidal injury, increases in spleen size, and the subsequent development of thrombocytopenia.Patients and MethodsWe retrospectively assessed the relationship between chemotherapy exposure, changes in spleen size (determined by volumetric measurements), and platelet counts in 136 patients treated with adjuvant fluorouracil and oxaliplatin (FOLFOX) or fluoropyrimidine for stage II or III colorectal adenocarcinoma. Hepatic sinusoidal injury and changes in spleen size were graded in a separate population of 63 patients with metastatic colorectal cancer receiving fluoropyrimidine and oxaliplatin before liver resection.ResultsSpleen size increased in 86% of patients treated with adjuvant FOLFOX (P < .001), with a >= 50% increase in 24% of patients. Spleen size did not significantly increase in patients treated with adjuvant fluoropyrimidine. Increases in spleen size correlated with cumulative oxaliplatin dose (P = .003). Patients with splenic enlargement >= 50% had higher rates of thrombocytopenia in the first year after completion of chemotherapy (27% v 5%; P = .003). In patients with hepatic metastases treated with preoperative fluoropyrimidine and oxaliplatin, increases in spleen size was a predictor of higher histologic grades of sinusoidal injury in both univariate (P = .03) and multivariate (P = .02) analyses.ConclusionIncreases in spleen size correlate with increasing grade of hepatic sinusoidal injury and can serve as a simple method for identifying patients at risk for this toxicity. Oxaliplatin-induced increases in spleen size should be recognized as a potential etiology of persistent thrombocytopenia after oxaliplatin treatment.