Invasive pulmonary aspergillosis in patients with hematologic malignancies: survival and prognostic factors

Abstract

Background and objectives: Despite improvements made in its early diagnosis and effective treatment, invasive pulmonary aspergillosis (IPA) remains a devastating opportunistic infection. In this retrospective study we have reviewed all consecutive cases of IPA diagnosed in adult patients with hematologic malignancies in our center from 1995 to 2000 to determine survival and prognostic factors.

Design and methods: Forty-one patients were included in the study. Ante-mortem classification of cases of IPA were: 4 definite, 10 highly probable, 19 probable and 8 possible cases; all these last eight patients were later upgraded to definite IPA at post-mortem examination. Clinical charts were reviewed and factors possibly affecting the outcome of IPA were analyzed.

Results: All but two patients received chemotherapy and/or immunosuppresive therapy before the onset of IPA (conventional chemotherapy = 24, allogeneic stem cell transplantation [SCT] = 12, autologous SCT = 3). At IPA diagnosis 28 patients were neutropenic (< 0.5 x 10(9)/L) for a median of 25 days (range 7-135), and 10 allogeneic SCT patients were receiving corticosteroids for graft-versus-host-disease. All but two patients received antifungal treatment for IPA. The median delay from diagnosis to start of therapy was two days (range 0-20). The median follow-up after the first symptom or sign of IPA was 42 days with a maximum follow-up of 61 months. The actuarial 4-month infection-free survival was 40% (95% CI 25% to 55%). Thirty-three patients died during follow-up and IPA was implicated in the patients' death in 24 cases (75%). In multivariate analysis prolonged survival was associated with recovery of neutropenia during treatment (p = 0.001) and not having received an allogeneic SCT (p = 0.003).

Interpretation and conclusions: Despite prompt initiation of antifungal therapy, survival of patients with a hematologic malignancy and IPA is currently low. Perhaps the introduction of more sensitive diagnostic methods will allow the onset of intensive therapy prior to the appearance of more advanced clinical symptoms and/or radiological signs, and the time will come to test whether earlier and more intensive therapy will improve survival.