[Clinical analysis of 14 cases with childhood acute lymphoblastic leukemia complicated with tropical candidemia]

Zhonghua Er Ke Za Zhi. 2020 Oct 2;58(10):813-817. doi: 10.3760/cma.j.cn112140-20200323-00298.
[Article in Chinese]

Abstract

Objective: To investigate the clinical feature, diagnosis, treatment and prognosis of childhood acute lymphoblastic leukemia (ALL) complicated with candida tropicalis bloodstream infection (CTBI), so as to improve the understanding of this disease. Methods: The general information, clinical manifestation, auxiliary examination, treatment and outcome of 14 childhood ALL who were diagnosed with tropical candidemia between January 2015 and December 2018 in 6 hospitals were analyzed retrospectively. Clinical data of non invasive fungal disease (IFD) ALL (28 cases) and other IFD children (9 cases) admitted in the same period were collected as control group. Logistic regression model was used to analyze the risk factor of CTBI. Results: Among 14 cases, there were 7 males and 7 females, with the age ranged from 17 months to 13 years. All the cases had fever, 9 cases had digestive system symptoms and stool fungal culture were positive in 3 of them; 7 cases had respiratory system symptoms and sputum fungal culture was positive in 1 of them; 2 cases had central nervous system symptoms and 10 cases progressed into septic shock. All 14 cases had neutropenia and the neutropenia duration was 1 to 53 days. Among 14 cases, the C-reactive protein was>50 mg/L in 8 cases, in which the proportion was significantly higher than that in other invasive fungal disease(IFD) (8/14 vs. 1/9, P<0.05), meanwhile the 1, 3-β-D-glucan detection, galactomannan detection and pulmonary imaging were not remarkable in all 14 cases. The blood culture results of 14 cases were all candida tropicalis, among which 13 cases finished drug susceptibility tests, the isolates of all cases were sensitive to flucytosine and amphotericin B, and the isolates of 4 cases were sensitive to fluconazole, voriconazole and itraconazole. Among 14 cases, 1 case lost to follow-up after giving up treatment, 1 case died before antifungal therapy and the remaining 12 cases received antifungal therapy; 7 of the 14 cases died. Univariate analysis showed that between ALL with CTBI group (14 cases) and ALL without invasive fungal disease (IFD) group (28 cases), the differences in variables such as ALL not in remission (χ²=37.847, P<0.01), length of hospital stay>15 days (χ2=8.351, P=0.004), neutropenia (χ²=14.280, P<0.01), neutropenia duration>10 days (χ²=10.254, P=0.001), use of broad-spectrum antibiotics (χ²=13.888, P<0.01), skin and mucous membrane damage (χ²= 5.923, P=0.015) were statistically significant. Conclusions: In childhood ALL complicated with tropical candidemia, the drug resistance rate and mortality rate were high. For azole-resistant tropical candida, amphotericin B liposome or echinocandins(caspofungin) -fluorocytosine combined therapy was recommended to reduce treatment-related deaths.

目的: 探讨儿童急性淋巴细胞白血病(ALL)合并热带念珠菌血症(CTBI)的临床特征、诊疗与预后,提高对该病的认识。 方法: 回顾性分析2015年1月至2018年12月在6家医院诊断的14例ALL合并CTBI患儿的一般资料、临床表现、辅助检查、治疗及转归情况。收集同期入院的无侵袭性真菌病(IFD)的ALL患儿(28例)及其他IFD患儿(9例)的临床资料作为对照组。采用Logistic回归分析探讨CTBI发生的危险因素。 结果: 14例患儿中男7例、女7例,年龄1岁5月龄~13岁。14例均有发热,9例有消化系统症状,3例粪培养有真菌;7例有呼吸系统症状,1例痰培养为真菌;2例有中枢神经症状;10例发生休克。14例患儿均有中性粒细胞缺乏,中性粒细胞缺乏持续时间1~53 d。C反应蛋白>50 mg/L的比例明显高于其他IFD病例(8/14比1/9,P<0.05),(1, 3)-β-D-葡聚糖、半乳甘露聚糖检测及肺部影像学无特异性。14例患儿血培养均可见热带念珠菌,13例完善药敏,均对氟胞嘧啶、两性霉素B敏感,4例对氟康唑、伏立康唑、伊曲康唑敏感。14例患儿中,1例放弃治疗后失访,1例在抗真菌治疗前死亡,余12例予抗真菌治疗;14例患儿中死亡7例。ALL合并CTBI组(14例)与ALL未发生IFD组(28例)在ALL未缓解(χ²=37.847,P<0.01)、住院时间>15 d(χ²=8.351,P=0.004)、中性粒细胞缺乏(χ²=14.280,P<0.01)、中性粒细胞缺乏时间>10 d(χ²=10.254,P=0.001)、应用广谱抗菌药物(χ²=13.888,P<0.01)、皮肤黏膜破损(χ²=5.923,P=0.015)方面差异有统计学意义。 结论: CTBI耐药率及病死率高,针对耐唑类热带念珠菌,推荐使用两性霉素B或棘白菌素+氟胞嘧啶联合治疗,降低治疗相关死亡风险。.

Keywords: Candida tropicalis; Child; Fungi; Leukemia.

MeSH terms

  • Adolescent
  • Antifungal Agents / therapeutic use
  • Candida
  • Candidemia* / complications
  • Candidemia* / drug therapy
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Retrospective Studies

Substances

  • Antifungal Agents