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接受低甲基化药物治疗患者感染的发生率及易感因素

Incidence and predisposing factors of infection in patients treated with hypomethylating agents.

作者信息

Kirkizlar Tugcan Alp, Kirkizlar Onur, Demirci Ufuk, Umut Aytug, Iflazoglu Huseyin, Umit Elif Gulsum, Demir Ahmet Muzaffer

机构信息

Trakya University Medical Faculty, Department of Hematology, Edirne, Turkey.

Trakya University Medical Faculty, Department of Internal Medicine, Edirne, Turkey.

出版信息

Leuk Res. 2023 Apr;127:107043. doi: 10.1016/j.leukres.2023.107043. Epub 2023 Feb 15.

Abstract

OBJECTIVE

Hypomethylating agents may have adverse effects such as cytopenias, cytopenia associated infections and fatality due to infections despite their favorable effects in the treatment of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The infection prophylaxis approach is based on expert opinions and real-life experiences. Hence, we aimed to reveal the frequence of infections, predisposing factors of infection and to analyse infection attributable mortality in patients with high-risk MDS, CMML and AML who received hypomethylating agents in our center where routine infection prophylaxis is not applied.

MATERIAL-METHOD: 43 adult patients with AML or high-risk MDS or CMML who received HMA ≥ 2 consecutive cycles from January 2014 to December 2020 were enrolled in the study.

RESULTS

43 patients and 173 treatment cycles were analyzed. The median age was 72 years and 61.3 % of patients were males. The distribution of the patients' diagnoses was; AML in 15 patients (34.9 %), high risk MDS in 20 patients (46.5 %), AML with myelodysplasia-related changes in 5 patients (11.6 %) and CMML in 3 patients (7 %). 38 infection events (21.9 %) occurred in 173 treatment cycles. 86.9 % (33 cycles) and 2.6 % (1 cycle) of infected cycles were bacterial and viral infections, respectively and 10.5 % (4 cycles) were bacterial and fungal concurrently. The most common origin of the infection was respiratory system. Hemoglobin count was lower and CRP level was higher at the beginning of the infected cycles significantly (p values were 0.002 and 0.012, respectively). Requirement of red blood cell and platelet transfusions were found to be significantly increased in the infected cycles (p values were 0.000 and 0.001, respectively). While > 4 cycles of treatment and increased platelet count were found to be protective against infection, > 6 points of Charlson Comorbidity Index (CCI) were found to increase the risk of infection. The median survival was 7.8 months in non-infected cycles while 6.83 months in infected cycles. This difference was not statistically significant (p value was 0.077).

DISCUSSION

The prevention and management of infections and infection-related deaths in patients treated with HMAs is crucial. Therefore, patients with a lower platelet count or a CCI score of > 6 may be candidates for infection prophylaxis when exposed to HMAs.

摘要

目的

尽管去甲基化药物在治疗急性髓系白血病(AML)、骨髓增生异常综合征(MDS)和慢性粒单核细胞白血病(CMML)方面具有良好疗效,但可能会产生诸如血细胞减少、血细胞减少相关感染以及因感染导致的死亡等不良反应。感染预防方法基于专家意见和实际经验。因此,我们旨在揭示在我们中心接受去甲基化药物治疗且未进行常规感染预防的高危MDS、CMML和AML患者的感染频率、感染的诱发因素,并分析感染所致死亡率。

材料与方法

纳入2014年1月至2020年12月期间连续接受≥2个周期去甲基化药物治疗的43例成年AML或高危MDS或CMML患者。

结果

分析了43例患者和173个治疗周期。中位年龄为72岁,61.3%的患者为男性。患者诊断分布为:AML 15例(34.9%),高危MDS 20例(46.5%),伴有骨髓增生异常相关改变的AML 5例(11.6%),CMML 3例(7%)。173个治疗周期中发生了38次感染事件(21.9%)。感染周期中86.9%(33个周期)为细菌感染,2.6%(1个周期)为病毒感染,10.5%(4个周期)为细菌和真菌混合感染。最常见的感染源是呼吸系统。感染周期开始时血红蛋白计数显著较低,CRP水平显著较高(p值分别为0.002和0.012)。发现感染周期中红细胞和血小板输注需求显著增加(p值分别为0.000和0.001)。虽然发现>4个周期的治疗和血小板计数增加对感染有保护作用,但Charlson合并症指数(CCI)>6分则增加感染风险。未感染周期的中位生存期为7.8个月,感染周期为6.83个月。这种差异无统计学意义(p值为0.077)。

讨论

去甲基化药物治疗患者的感染预防及管理至关重要。因此,血小板计数较低或CCI评分>6的患者在接受去甲基化药物治疗时可能是感染预防的候选对象。

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