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奥曲肽作为化学保护剂成功用于预防聚乙二醇天冬酰胺酶诱导的胰腺炎。

Successful use of octreotide as a chemoprotectant for prevention of PEG-asparaginase-induced pancreatitis.

作者信息

Buie Larry W, Moore Joseph, van Deventer Hank

机构信息

Department of Pharmacy, University of North Carolina Health Care, Chapel Hill, North Carolina; Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina.

出版信息

Pharmacotherapy. 2014 Aug;34(8):e149-51. doi: 10.1002/phar.1460.

Abstract

l-asparaginase is an aminohydrolase that deprives leukemia cells of l-asparagine required for protein synthesis. Although studies in patients with acute lymphoblastic leukemia have shown that the addition of l-asparaginase improved the overall remission rate, life-threatening acute pancreatitis has occurred in 0.5-4% of patients. We describe the first adult case report, to our knowledge, of the successful use of octreotide as a chemoprotectant for the prevention of recurrent pegylated asparaginase (PEG-ASP)-induced pancreatitis in a 21-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukemia. After recurrent PEG-ASP administration during induction chemotherapy, he developed necrotizing pancreatitis, confirmed by abdominal computed tomography, and further asparaginase therapy was withheld. Currently, there are no specific treatment recommendations for the management of asparaginase-induced pancreatitis other than drug discontinuation. After disease relapse, a pediatric PEG-ASP-containing regimen was initiated, and PEG-ASP therapy was resumed due to its potential clinical benefit. Octreotide 100 μg subcutaneously 3 times/day, utilized as a chemoprotectant, was found to prevent pancreatitis recurrence. The patient completed therapy and was able to receive a bone marrow transplant without further complications from PEG-ASP therapy. Based on this patient's experience, we believe it is reasonable to reincorporate PEG-ASP after an episode of pancreatitis with use of octreotide as a chemoprotectant; however, this conclusion will need to be substantiated in a randomized clinical trial with a larger group of patients.

摘要

L-天冬酰胺酶是一种氨基水解酶,可使白血病细胞缺乏蛋白质合成所需的L-天冬酰胺。尽管对急性淋巴细胞白血病患者的研究表明,添加L-天冬酰胺酶可提高总体缓解率,但0.5%-4%的患者发生了危及生命的急性胰腺炎。据我们所知,我们描述了首例成功使用奥曲肽作为化学保护剂预防一名21岁费城染色体阴性急性淋巴细胞白血病男性复发性聚乙二醇化天冬酰胺酶(PEG-ASP)诱导的胰腺炎的成人病例报告。在诱导化疗期间反复给予PEG-ASP后,他出现了坏死性胰腺炎,经腹部计算机断层扫描证实,随后停止了进一步的天冬酰胺酶治疗。目前,除停药外,对于天冬酰胺酶诱导的胰腺炎的治疗尚无具体的治疗建议。疾病复发后,启动了含儿科PEG-ASP的方案,由于其潜在的临床益处,恢复了PEG-ASP治疗。发现每天皮下注射3次100μg奥曲肽作为化学保护剂可预防胰腺炎复发。患者完成了治疗,并且能够接受骨髓移植,而没有PEG-ASP治疗带来的进一步并发症。基于该患者的经验,我们认为在胰腺炎发作后使用奥曲肽作为化学保护剂重新使用PEG-ASP是合理的;然而,这一结论需要在更大规模患者的随机临床试验中得到证实。

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