Breakthrough Mucormycosis In Two Cases Of Hematological Malignancies Successfully Treated With Amphotericin B Colloidal Dispersion

Yang Xu, Yin Liu, Mingming Hu, B. Song, X. Kong, Zhihong Lin, Jian Zhang, H. Qiu
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Abstract

Background: Patients with hematologic malignancies have poor immunity, and they are more vulnerable to fungal invasion because of disease characteristics and clinical treatment such as chemotherapy. Mucor infections in hematologic malignancies are rare, but once occurred usually lead to high mortality. In this study, we report two cases of hematologic malignancies complicated with breakthrough mucormycosis (BT-MCR), which were treated with amphotericin B colloidal dispersion (ABCD) combined with or without other antifungal agents. Case Presentation: Case 1 shows a patient with natural killer cell leukemia, type 2 diabetes, and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This patient was admitted to the First Affiliated Hospital of Soochow University because of fever with cough and expectoration for a week. Next-generation sequencing (NGS) of alveolar lavage fluid revealed that the patient was infected with Rhizomucor pusillus and Enterococcus faecalis. This patient was infected with fungi although he had taken voriconazole for prevention. Considering the renal toxicity of amphotericin B deoxycholate, the patient received ABCD via intravenous drip combined with posaconazole via oral administration for Rhizomucor pusillus infection and meropenem via intravenous drip for Enterococcus faecalis infection during 45 days of treatment. The patient was free of complaints in the next 2-month follow-up. Case 2 represents a patient with acute myeloid leukemia. During induction chemotherapy, the patient presented with weakness of the left limbs, and head MRI showed multiple cerebral infarctions (MCI). In addition, he had high fever with right-face swelling and pain, and the NGS of blood revealed that he had Mucor circinelloides and Stenotrophomonas maltophilia infection. ABCD and ceftazidime/avibactam were administered to the patients via intravenous drip. The patient also achieved complete remission after later consolidation chemotherapy and successfully underwent allo-HSCT. Conclusion: ABCD shows great efficiency with or without other antifungal agents in treating hematological malignancies complicated with BT-MCR. Despite its infusion-related adverse effects and nephrotoxicity, ABCD shows great application potential for patients with hematologic malignancies, who are often more susceptible to fatal BT-MCR. Furthermore, more valid data should be collected on the combination therapy (ABCD and posaconazole).
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两性霉素B胶状分散体成功治疗血液系统恶性肿瘤2例突破性毛霉病
背景:血液学恶性肿瘤患者自身免疫力较差,由于疾病特点及化疗等临床治疗,更容易受到真菌侵袭。恶性血液病的毛霉菌感染是罕见的,但一旦发生通常导致高死亡率。在这项研究中,我们报告了两例血液系统恶性肿瘤合并突破性毛霉菌病(BT-MCR),这是两性霉素B胶体分散剂(ABCD)联合或不联合其他抗真菌药物治疗。病例介绍:病例1显示了一个在异基因造血干细胞移植(alloo - hsct)后患有自然杀伤细胞白血病、2型糖尿病和移植物抗宿主病的患者。患者因发热咳嗽咳痰一周入住东吴大学第一附属医院。肺泡灌洗液的新一代测序(NGS)显示患者感染了脓疱根瘤菌和粪肠球菌。该患者虽服用伏立康唑预防,但仍感染真菌。考虑到两性霉素B去氧胆酸盐的肾毒性,患者静脉滴注ABCD联合口服泊沙康唑治疗脓疱根瘤菌感染,静脉滴注美罗培南治疗粪肠球菌感染,疗程45天。在接下来的2个月随访中,患者无主诉。病例2为急性髓性白血病患者。在诱导化疗期间,患者表现为左四肢无力,头部MRI显示多发性脑梗死(MCI)。患者高热,右脸肿痛,血液NGS提示为环状毛霉及嗜麦芽窄养单胞菌感染。静脉滴注ABCD和头孢他啶/阿维巴坦。患者在后来的巩固化疗后也获得了完全缓解,并成功接受了同种异体造血干细胞移植。结论:ABCD联合或不联合其他抗真菌药物治疗血液系统恶性肿瘤合并BT-MCR疗效显著。尽管ABCD具有输注相关的不良反应和肾毒性,但它在血液系统恶性肿瘤患者中显示出巨大的应用潜力,这些患者往往更容易发生致命的BT-MCR。此外,应该收集更多有效的联合治疗数据(ABCD和泊沙康唑)。
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