Invasive aspergillosis in haematological malignancies: Clinical findings and management for intensive chemotherapy completion

Abstract

Sixty-one cases of Aspergillus infection (35 acute myeloid leukemia, 15 acute lymphoid leukemia, one myelodysplastic syndrome, two aplastic anemia, eight non-Hodgkin's lymphoma) seen in our department between January 1989 and July 1999 were studied retrospectively to evaluate the clinical characteristics, to ascertain the factors that influenced the outcome from mycotic infections, and whether early diagnosis and prolonged therapy permitted completion of scheduled intensive chemotherapy and bone marrow transplantation (BMT) without fungal recurrence. The patients were divided into three diagnostic categories: proven aspergillosis (autoptic or histologic diagnosis) n = 39, probable aspergillosis (radiological diagnosis with positive microbiology) n = 9, and possible aspergillosis (radiological diagnosis alone) n = 13. In the same period among 675 acute leukemia patients the incidence of proven or probable aspergillosis was 7.1%. At onset of infection 92% of patients were neutropenic (< 0.5 3 10 9 /L). The most frequent site of infection was the lung (90%); disseminated disease was present in 20 patients. Among 44 assessable patients, 12 (27%) failed to respond to early antifungal therapy and died. Thirty-two patients were cured with antifungal treatment, three of five nonneutropenic with only itraconazole, the others with amphotericin B 1 mg/Kg/day with or without itraconazole subsequently or with liposomal amphotericin, Ambisome, if renal toxicity occurred. Twenty-four of 29 neutropenic responders, all affected by acute leukemia, continued scheduled intensive chemotherapies. Pulmonary lobectomy was successfully combined with medical treatment in two cases before scheduled BMT. After infection nine patients were submitted to BMT (six allo, one marrow unrelated donor (MUD), two auto) with Ambisome or itraconazole as secondary prophylaxis without fungal relapse (followup: 25---99 months). The median time from fungal infection to transplant was five months, range 3---10. Thirteen of 29 surviving patients had leukemia relapse, but only three (23%) of these showed also fungal infection recurrence. In conclusion, a high index of suspicion and careful clinical and radiological examinations are the key to identifying infected patients early and to programming the following therapeutic steps. Above all in leukemia patients, prompt and aggressive administration of antifungal agents seems to improve the outcome of invasive fungal disease and to permit intensive chemotherapy completion and transplant. Am.

Voriconazole in the management of invasive aspergillosis in two patients with acute myeloid leukemia undergoing stem cell transplantation

“…What is universally agreed is that a history of IA is not an absolute contraindication to further chemotherapy and SCT. 10,[17][18] Ideally, patients needing further treatment for leukemia should undergo surgical excision of the pulmonary lesions, but this is often impossible due to the impending risk of leukemia relapse or the presence of multiple, bilateral lesions. In any case, even surgical excision does not guarantee complete cure, since aspergillosis is usually a multifocal disease, at least at microscopic level.…”

“…8 have also suggested the possible efficacy of oral itraconazole (ITR) and liposomal amphotericin B (L AmB) for this indication. [9][10][11] In any case, even with prophylaxis, the relapse rate remains very high (33%), with a mortality rate among relapsed patients of 88%. 12 Therefore, there is a clear need for new strategies for patients undergoing SCT who have a history of IA.…”

Use of Bronchoalveolar Lavage To Detect Galactomannan for Diagnosis of Pulmonary Aspergillosis among Nonimmunocompromised Hosts

“…At present, lung biopsies are the diagnostic "gold standard" but are limited by sensitivity and complications (13). While the isolation of Aspergillus species from the respiratory tracts of high-risk patients is predictive of pulmonary aspergillosis (6,21), culture is limited by poor sensitivity.…”

Isobolographic Analysis of Pharmacodynamic Interactions between Antifungal Agents and Ciprofloxacin against Candida albicans and Aspergillus fumigatus

“…are the most common pathogens causing life-threatening invasive fungal infections in immunocompromised patients (22,25,41). Patients at risk for these invasive fungal infections are also at risk of developing other opportunistic infections, for which a wide range of nonantifungal therapeutic agents is used for prophylactic and therapeutic purposes concomitantly with antifungal agents (2).…”