两性霉素B胆固醇硫酸酯复合物治疗恶性血液病合并侵袭性真菌病研究

Study of amphotericin B cholesterol sulfate complex in the treatment of malignant hematological diseases complicated with invasive mycosis

目的探讨两性霉素B胆固醇硫酸酯复合物(ABCD)治疗恶性血液病合并侵袭性真菌病(IFD)的疗效及安全性。方法回顾性分析2021年6月至2022年7月就诊于南方医科大学南方医院血液科的34例恶性血液病合并IFD患者应用ABCD的疗效及不良反应。结果34例恶性血液病患者,白血病28例(82.4%),骨髓增生异常综合征4例(11.8%),淋巴瘤2例(5.9%);其中异基因造血干细胞移植13例。31例诊断肺部真菌感染,6例合并其他部位真菌感染。8例采用高通量测序技术(NGS)检测到真菌病原体,其中仅3例血培养显示阳性,提示NGS在诊断中具有较好的灵敏度和特异度。随访时间97.5(6.0~121.0)d,疗效评判有效22例,无效12例,总有效率64.7%,有效组与无效组对比,患者的原发病缓解情况差异具有统计学意义(P=0.001),患者是否接受移植、粒细胞缺乏程度、持续时间等差异无统计学意义(P>0.05)。30 d、100 d累积生存率分别为79%、71%。31例(91.2%)出现输液相关反应(IRRs),最常见为发热(93.5%)和寒战(35.5%)。7例(20.6%)发生肾功能损害,减停药物后好转。18例(52.9%)发生低钾血症,血钾水平2.95(2.34~3.38)mmol/L。结论ABCD在治疗恶性血液病合并侵袭性真菌病中有较好的疗效,且毒副反应小,早期应用患者获益可能更大。

Objective To explore the efficacy and safety of amphotericin B colloidal dispersion(ABCD)in patients with hematologic malignancies complicated with invasive fungal disease(IFD).Methods Retrospectively analyzed the efficacy and adversein 34 patients with hematologic malignancies complicated with IFD in Nanfang Hospital of Southern Medical University from June 2021 to July 2022.Results Among the 34 patients,there were 28(82.4%)patients with leukemia,4(11.8%)patients with myelodysplastic syndrome and 2(5.9%)patients with lymphoma.31 patients were diagnosed with pulmonary fungal infection,and 6 patients combined with other organs fungal infection.The median follow-up was 97.5(6.0-121.0)days,and the overall responserateof 64.7%.The efficacy was related to the remission of the primary disease(P=0.001),but not to whether the patient received a transplant,thedegree or duration of agranulocytosis(P>0.05).The 30-day and 100-day cumulative survival rates were 79%and 71%.Infusion-related reactions(IRRs)were the most common adverse reactions(31/34,91.2%).Only 7 patients(20.6%)with a nephrotoxicity.18 patients(52.9%)developed hypokalemia during treatment,and the median serum potassium level was 2.95(2.34-3.38)mmol/L.Conclusion Due to broader antibacterial spectrum and less drug resistance,ABCD is safe and effective for hematologic malignancies complicated withIFD.