Department of Pharmacy, Iowa City Veterans Affairs Health Care System, Iowa City, Iowa.
Corresponding Author: Delaney R. Brainerd, PharmD, Iowa City VA Health Care System (Mailstop 119), 601 Hwy 6 W, Iowa City, IA 52246 (
J Clin Psychiatry. 2024 May 15;85(2):23m15149. doi: 10.4088/JCP.23m15149.
The objective of this study was to examine the relationship between clozapine use and hematologic malignancies, using national administrative data from the United States Veterans Health Administration (VHA). This case-control study of veterans with schizophrenia matched cases with incident hematologic malignancy to 10 controls without hematologic malignancy by gender, age, and time since first schizophrenia diagnosis from October 1999, the beginning of VHA data archives, to June 2022. Schizophrenia diagnoses were identified using , code 295.x and codes F20.x and F25.x from inpatient hospitalization and outpatient encounter data. Additional inclusion criteria were age 18-85 years, no prior history of malignancy, and at least 1 year of antipsychotic exposure. Clozapine exposure was assessed using 3 metrics: any exposure, years of exposure, and cumulative defined daily doses (DDD). Conditional multivariable logistic regression was used to adjust for nonmatched confounding variables. A total of 2,306 veterans with schizophrenia were identified with an incident diagnosis of hematologic malignancy and matched to 23,043 controls. Any prior clozapine exposure was more commonly observed among cases (5.3%) than controls (4.1%) and was significantly different after adjustment (odds ratio [OR], 1.31; 95% CI, 1.08-1.60). Risk was dose-dependent, where cumulative clozapine exposures from 3,000 to 4,999 DDD (OR, 1.78; 95% CI, 1.13-2.79) and ≥5,000 DDD (OR, 1.81; 95% CI, 1.24-2.64) were significantly associated with malignancy risk. Similarly, clozapine exposure of 5 or more years was associated with malignancy risk (OR, 1.88; 95% CI, 1.43-2.47). Consistent with prior report, this study observed an increased risk of hematologic malignancy associated with clozapine exposure. These findings suggest patients receiving clozapine use, particularly those with long-term use, should be closely monitored for hematologic malignancy.
这项研究的目的是利用美国退伍军人健康管理局（VHA）的国家行政数据，研究氯氮平使用与血液系统恶性肿瘤之间的关系。这项针对患有精神分裂症的退伍军人的病例对照研究，根据性别、年龄和从 1999 年 10 月 VHA 数据档案开始到 2022 年 6 月首次诊断为精神分裂症后的时间，将血液系统恶性肿瘤的发病病例与 10 名无血液系统恶性肿瘤的对照进行匹配。精神分裂症的诊断是通过住院和门诊就诊数据中的 295.x 和 F20.x 及 F25.x 代码确定的。其他纳入标准为年龄 18-85 岁、无恶性肿瘤病史和至少 1 年的抗精神病药物暴露史。氯氮平的暴露情况通过 3 个指标进行评估：任何暴露、暴露年限和累积限定日剂量（DDD）。采用条件多变量逻辑回归来调整非匹配的混杂变量。共确定了 2306 名患有精神分裂症的退伍军人患有血液系统恶性肿瘤，将他们与 23043 名对照进行匹配。在病例中更常见到有任何先前的氯氮平暴露（5.3%），而对照中则较少见（4.1%），且调整后差异有统计学意义（比值比[OR]，1.31；95%置信区间[CI]，1.08-1.60）。风险呈剂量依赖性，累积氯氮平暴露量在 3000-4999 DDD（OR，1.78；95% CI，1.13-2.79）和≥5000 DDD（OR，1.81；95% CI，1.24-2.64）时与恶性肿瘤风险显著相关。同样，氯氮平暴露≥5 年也与恶性肿瘤风险相关（OR，1.88；95% CI，1.43-2.47）。与先前的报告一致，本研究观察到氯氮平暴露与血液系统恶性肿瘤的风险增加相关。这些发现表明，接受氯氮平治疗的患者，特别是长期使用的患者，应密切监测血液系统恶性肿瘤。
