米卡芬净预防诱导化疗的急性白血病患者。
Micafungin prophylaxis for acute leukemia patients undergoing induction chemotherapy.
机构信息
Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
出版信息
BMC Cancer. 2019 Apr 16;19(1):358. doi: 10.1186/s12885-019-5557-9.
BACKGROUND
Micafungin is a well-tolerated and effective prophylactic antifungal agent used in hematologic diseases. In this prospective trial, we evaluated the efficacy and safety of prophylactic micafungin during first induction chemotherapy in patients with acute leukemia. We also compared outcomes of prophylactic micafungin with those of prophylactic posaconazole in acute myeloid leukemia (AML).
METHODS
Medically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity ( Clinicaltrials.gov number, NCT02440178). The primary end point was incidence of invasive fungal infection, and the secondary end points were adverse events of prophylactic micafungin and mortality during induction therapy.
RESULTS
The 65 patients (median age = 51 years, male:female = 34:31) enrolled in this study had diagnoses of AML (33, 50.8%), acute lymphoblastic leukemia (31, 47.7%), and acute biphenotypic leukemia (1, 1.5%). Median duration of micafungin treatment was 24 days (range 1-68), with proven invasive fungal disease in one patient (1.5%) and possible fungal infection in two patients (3.1%). Three of the patients (4.6%) experienced the following adverse events, but all events were tolerable: liver function abnormality (Grade 2, n = 1; Grade 3, n = 1) and allergic reaction (Grade 2, n = 1). Three patients died during induction therapy, and invasive aspergillosis pneumonia was the cause of death for one of those patients. Overall, 19 patients (29.2%) discontinued prophylactic micafungin, and 18 (27.7%) patients switched to another antifungal agent. We observed no fungal infections caused by amphotericin B-resistant organisms. In AML patients, outcomes of prophylactic micafungin during induction chemotherapy did not differ significantly with those of prophylactic posaconazole with regard to incidence of fungal infections, rate of discontinuation, or safety.
CONCLUSIONS
Our study demonstrates that prophylactic micafungin is safe and effective in patients with acute leukemia undergoing induction chemotherapy. Outcomes in patients with AML were similar to those of prophylactic posaconazole, indicating the usefulness of micafungin as a prophylactic antifungal agent during induction chemotherapy for AML.
TRIAL REGISTRATION
Clinicaltrials.gov NCT02440178, registered May 12th 2015.
背景
米卡芬净是一种耐受性良好且有效的预防用抗真菌药物，用于血液系统疾病。在这项前瞻性试验中，我们评估了米卡芬净在急性白血病患者首次诱导化疗中的预防效果和安全性。我们还比较了米卡芬净预防与泊沙康唑预防在急性髓系白血病（AML）中的效果。
方法
新诊断为急性白血病且身体状况适宜的患者在首次诱导化疗开始时接受 50mg 米卡芬净静脉注射，每天一次，直至中性粒细胞计数恢复、疑似真菌感染或出现不可接受的药物相关毒性（Clinicaltrials.gov 编号：NCT02440178）。主要终点为侵袭性真菌感染的发生率，次要终点为米卡芬净预防的不良事件和诱导治疗期间的死亡率。
结果
这项研究共纳入 65 例患者（中位年龄 51 岁，男：女=34:31），诊断为 AML（33 例，50.8%）、急性淋巴细胞白血病（31 例，47.7%）和急性双表型白血病（1 例，1.5%）。米卡芬净治疗的中位持续时间为 24 天（范围 1-68 天），1 例（1.5%）患者发生确诊的侵袭性真菌感染，2 例（3.1%）患者发生可能的真菌感染。3 例（4.6%）患者出现以下不良事件，但所有事件均耐受：肝功能异常（2 级 1 例，3 级 1 例）和过敏反应（2 级 1 例）。3 例患者在诱导治疗期间死亡，其中 1 例患者的死因是侵袭性曲霉菌肺炎。总体而言，19 例（29.2%）患者停止了米卡芬净预防，18 例（27.7%）患者改用了另一种抗真菌药物。我们未观察到由两性霉素 B 耐药菌引起的真菌感染。在 AML 患者中，米卡芬净预防在诱导化疗期间的真菌感染发生率、停药率或安全性方面与泊沙康唑预防均无显著差异。
结论
我们的研究表明，米卡芬净在接受诱导化疗的急性白血病患者中是安全且有效的。AML 患者的结局与泊沙康唑预防相似，表明米卡芬净作为 AML 诱导化疗期间的预防用抗真菌药物是有用的。
试验注册
Clinicaltrials.gov NCT02440178，于 2015 年 5 月 12 日注册。
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