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

Sixty-one cases of Aspergillus infection (35 acute myeloid leukemia, 15 acu te lymphoid leukemia, one myelodysplastic syndrome, two aplastic anemia, ei ght non-Hodgkin's lymphoma) seen in our department between January 1989 and July 1999 were studied retrospectively to evaluate the clinical characteri stics, to ascertain the factors that influenced the outcome from mycotic in fections, and whether early diagnosis and prolonged therapy permitted compl etion of scheduled intensive chemotherapy and bone marrow transplantation ( BMT) without fungal recurrence. The patients were divided into three diagno stic categories: proven aspergillosis (autoptic or histologic diagnosis) n = 39, probable aspergillosis (radiological diagnosis with positive microbio logy) n = 9, and possible aspergillosis (radiological diagnosis alone) n = 13. In the same period among 675 acute leukemia patients the incidence of p roven or probable aspergillosis was 7.1%. At onset of infection 92% of pati ents were neutropenic (<0.5 x 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 the rapy and died. Thirty-two patients were cured with antifungal treatment, th ree of five nonneutropenic with only itraconazole, the others with amphoter icin B 1 mg/Kg/day with or without itraconazole subsequently or with liposo mal amphotericin, Ambisome, if renal toxicity occurred. Twenty-four of 29 n eutropenic responders, all affected by acute leukemia, continued scheduled intensive chemotherapies. Pulmonary lobectomy was successfully combined wit h 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 infect ion to transplant was five months, range 3-10. Thirteen of 29 surviving pat ients had leukemia relapse, but only three (23%) of these showed also funga l infection recurrence. In conclusion, a high index of suspicion and carefu l clinical and radiological examinations are the key to identifying infecte d patients early and to programming the following therapeutic steps. Above all in leukemia patients, prompt and aggressive administration of antifunga l agents seems to improve the outcome of invasive fungal disease and to per mit intensive chemotherapy completion and transplant. (C) 2001 Wiley-Liss, Inc.