Nosari A, Oreste P, Montillo M, Carrafiello G, Draisci M, Muti G, Molteni A, Morra E
Department of Hematology, Niguarda Cà Granda Hospital, piazza Ospedale Maggiore 3, 20160 Milan, Italy.
Haematologica. 2000 Oct;85(10):1068-71.
In recent years pulmonary mucormycosis has been reported in patients with leukemia and lymphoma and bone marrow transplant recipients. It carries an extremely poor prognosis. We report our experience of clinical findings, diagnostic procedures, treatment and outcome of mucormycosis diagnosed in neutropenic patients affected by hematologic neoplasms admitted to our Department.
From November 1987 to July 1999 we observed 13 cases of Mucor. Their median age was 61 years (range 20-75), and they were predominantly in the aplastic post-chemotherapy period (12/13), affected by acute myeloid leukemia (11 cases ) or non-Hodgkin's lymphoma (2 cases). Six patients (all with leukemia) were receiving inductionEth consolidation therapy, 7 had progressive hematologic disease. At the onset of infection all patients were neutropenic (N < 0.5x10(9)/L). No patients had diabetes mellitus. Two patients had been receiving steroid therapy for 5 and 7 days.
The lung was involved in all cases (13/13); disseminated disease was present in 8/13 patients. All cultures (blood, sputum, nasal swabs and bronchoalveolar lavage) were negative. In 3 patients a histologic diagnosis was made in vivo: in 1 patient by percutaneous pulmonary biopsy, in 1 patient by pulmonary lobectomy, and in the last patient by percutaneous pulmonary biopsy confirmed by excision of a cerebellar abscess. In the remaining 10 cases diagnosis was made post-mortem. Five patients were not treated, 2 because of poor clinical condition and 3 because fungal infection was not suspected. Amphotericin B (1 mg/kg/day) was given empirically to 6 patients and 2 responded to treatment. The remaining 2 patients with neurologic symptoms at the onset of infection were treated with liposomal amphotericin, Ambisome, one with 3 and one with 5 mg/kg/day; of these two patients the first died in 4 days; the second, with both pulmonary and cerebellar localizations, was treated successfully with 5 mg/kg/day for 4 weeks and then with 3 mg/kg/day, and excision of a brain abscess at neutrophil recovery (total dose of Ambisome: 12,000 mg). The 3 surviving leukemic patients were able to complete subsequent consolidation therapy using amphotericin B or liposomal amphotericin as secondary prophylaxis during aplasia.
In neutropenic hematologic patients Mucor is rarely suspected. In our patients infection was often characterized by disseminated disease and a rapidly fatal course; only early aggressive amphotericin B (or Ambisome) treatment together with neutrophil recovery appeared to improve the outcome. Diagnosis is very important for programming antifungal therapy and secondary prophylaxis with amphotericin B, because Mucor is usually resistant to itraconazole.
近年来，白血病、淋巴瘤患者及骨髓移植受者中已报告发生肺毛霉病，其预后极差。我们报告了在我院血液科住院的血液系统肿瘤所致中性粒细胞减少患者中诊断为毛霉病的临床发现、诊断方法、治疗及转归情况。
1987年11月至1999年7月，我们观察了13例毛霉病患者。他们的中位年龄为61岁（范围20 - 75岁），主要处于化疗后再生障碍期（12/13），其中11例为急性髓系白血病，2例为非霍奇金淋巴瘤。6例患者（均为白血病患者）正在接受诱导及巩固治疗，7例患者患有进展性血液系统疾病。感染发生时所有患者均为中性粒细胞减少（N < 0.5×10⁹/L）。无患者患有糖尿病。2例患者接受了5天和7天的类固醇治疗。
所有病例（13/13）均累及肺部；8/13患者存在播散性疾病。所有培养（血液、痰液、鼻拭子及支气管肺泡灌洗）均为阴性。3例患者在生前做出了组织学诊断：1例通过经皮肺活检，1例通过肺叶切除术，最后1例通过经皮肺活检并经小脑脓肿切除证实。其余10例在死后做出诊断。5。5例患者未接受治疗，2例因临床状况差，3例因未怀疑真菌感染。6例患者经验性给予两性霉素B（1mg/kg/天），2例治疗有效。另外2例感染开始时伴有神经症状的患者接受了脂质体两性霉素（安必素）治疗，1例给予3mg/kg/天，1例给予5mg/kg/天；这2例患者中，第1例在4天内死亡；第2例同时有肺部和小脑病变，接受5mg/kg/天治疗4周，然后3mg/kg/天治疗，并在中性粒细胞恢复时切除脑脓肿（安必素总剂量：12000mg）。3例存活的白血病患者在再生障碍期能够使用两性霉素B或脂质体两性霉素作为二级预防完成后续巩固治疗。
在中性粒细胞减少的血液系统患者中很少怀疑毛霉病。在我们的患者中，感染常以播散性疾病和快速致命病程为特征；只有早期积极的两性霉素B（或安必素）治疗以及中性粒细胞恢复似乎能改善转归。诊断对于规划抗真菌治疗及两性霉素B的二级预防非常重要，因为毛霉通常对伊曲康唑耐药。
