Mucormycosis in hematologic malignancies: an emerging fungal infection

Background and Objectives, In recent years pulmonary mucormycosis has been reported in patients with leukemia and lymphoma and bone marrow plant recipients. It carries an extremely poor prognosis. We report our experience of clinical findings, diagnostic procedures, treatment and outcome mucormycosis diagnosed in neutropenic patients affected by hematologic neoplasms admitted to our departments. Design and Methods. From November 1987 to July 1999 we observed 13 patients with mucormycosis. 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 tall with leukemia) were receiving induction-consolidation therapy, 7 had progressive hematologic disease. At the onset 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. Results. 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 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 cerebellar abscess. In the remaining 10 cases diagnosis was made post-mortem. Five patients were :treated, 2 because of poor clinical condition and because fungal infection was not suspected. Amphotericin B (1 mg/kg/day) was given empirically 6 patients and 2 responded to treatment. remaining 2 patients with neurologic symptoms le onset of infection were treated with liposomal amphotericin, Ambisome(R), one with 3 and one with 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(R): 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. Interpretation and Conclusions. Mucormycosis in neutropenic hematologic patients 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(R)) 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.