Paraplegia and Paraparesis From Intrathecal Methotrexate and Cytarabine Contaminated With Trace Amounts of Vincristine in China During 2007

Author:

Zeng Guang1,Ma Huilai1,Wang Xiangbo1,Yan Huifang1,Wan Xinhua1,Jiang Bin1,Fontaine Robert E.1,Wu Zhenglai1,Lin Shaobin1,Ruan Feng1,Liu Huihui1

Affiliation:

1. From the Chinese Center for Disease Control and Prevention, Chinese Field Epidemiology Training Program; National Institute for Occupational Health and Poison Control; National Institute for Environmental Health and Related Product Safety; Xuan Wu Hospital, Capital Medical University; Peking Union Medical College; Peking University People's Hospital, Beijing, China; and Centers for Disease Control and Prevention, Atlanta, GA.

Abstract

Purpose The production and administration of drugs used intrathecally requires special care to prevent contamination with neurotoxic agents. In 2007, we investigated a widespread outbreak of paraplegia and paraparesis among Chinese patients who received intrathecal drugs to identify the presumed contaminant and its source to prevent further cases. Patients and Methods We defined a case as onset from January 1 to October 31, 2007, of bilateral flaccid paraparesis or paraplegia or retention and incontinence of stool or urine, in a patient receiving intrathecal drugs. Using a retrospective cohort approach, we selected 12 hospitals from all hospitals that had reported cases. In these hospitals, we identified all 448 patients (including 107 cases) who received intrathecal chemotherapy or chemoprophylaxis in 2007. We calculated attack rates and Mantel-Haenszel adjusted risk ratios for intrathecal drug type and lot. Results All 12 hospitals used intrathecal methotrexate or cytarabine produced by one pharmaceutical plant. Only two lots of each drug were associated with cases. Lot-specific attack rates ranged from 42% to 100% (risk ratio, ∞; lower confidence bounds, 1.8 to 7.3). Vincristine production had immediately preceded production of the implicated lots on the same equipment. By using ultra performance liquid chromatography, we detected vincristine (0.28 to 18 μg) in unused vials from implicated lots of methotrexate and cytarabine. Conclusion Trace amounts of vincristine that contaminated intrathecal drugs caused a large outbreak of severe neurologic damage. Vincristine and other neurotoxic drugs should not be produced on any equipment that is also used for producing drugs that are to be administered intrathecally.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Building Global Epidemiology and Response Capacity with Field Epidemiology Training Programs;Emerging Infectious Diseases;2017-12

2. Methotrexate;Critical Care Toxicology;2017

3. Methotrexate;Critical Care Toxicology;2016

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