As much as one-third of patients develop fever and flu-like symptoms after fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) for yet unknown reasons. The aim of the present study was to investigate factors mediating these side effects. Fifty consecutive patients with various pulmonary diseases who underwent FOB without further interventions (n = 30) or combined with BAL (n = 20) were enrolled. Serum levels of the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha were determined directly prior to (t0), directly after (t1), and 6 h after (t2) the procedures by ELISA. In parallel, blood cultures were drawn at t2. At to and t1, generally only low cytokine concentrations could be detected. At t2, however, significant increases of cytokine levels were found. IL-6 and TNF-alpha were significantly higher in patients after BAL than in patients after FOB. Comparing patients who developed fever (n = 12) with those who did not (n = 38), irrespective of the endoscopic procedures performed, dramatic increases of all three cytokines were detected in febrile patients that were significantly higher than in patients without fever. In the FOB group only patients who received local anesthesia by prilocaine bolus injection into the airways via the working channel of the bronchoscope developed fever and increases of IL-6 and IL-beta, whereas patients anaesthetized by inhalation of a prilocaine aerosol remained afebrile and had slight IL-6 increases only. There was a highly significant correlation between IL-6 values at t2 and the number of BAL alveolar macrophages (r = 0.98). All blood cultures remained sterile. These results indicate that fever after FOB and BAL is induced by proinflammatory cytokines derived from alveolar macrophages activated by instillation of fluid into the airways.
28 patients with high-risk acute lymphoblastic (ALL) or acute myelogenous leukemia (AML) underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors because of one or several contraindications against myeloablative conditioning. Out of 28 patients, nine (32%) had pulmonary or hepatosplenic infiltrates due to invasive fungal infections (IFI) before NST. Out of a total of 28 patients, 17 (61%) had uncontrolled leukemia before NST. Conditioning was performed with fludarabine 180 mg/m(2), busulfan 8 mg/kg and antithymocyte globulin 40 mg/kg. After NST, fever of unknown origin, sepsis or pneumonia developed in 18/28 patients (64%) overall. IFI reactivated in 3/9 patients after NST. Out of, 28 patients, 13 (46%) had late onset of acute graft-versus-host disease (GvHD), which developed at a median of 83 days after NST. GvHD frequently developed after donor lymphocyte infusions. After a median follow-up of 8 months (2-46 months), 14/28 patients (50%) have died from relapse and 1/28 patients (4%) has died from sepsis. Among 28 patients, 13 (46%) are alive in complete remission (CR). Six of 17 patients (35%) with uncontrolled disease and 7/11 patients (63%) with CR before NST are alive in CR. Probability of overall survival at 2 years is 38%. In summary, NST offers a therapeutic alternative to patients with high-risk ALL or AML, who have contraindications against conventional high-dose conditioning. Low NRM was encountered despite high morbidity, but relapse rate was high. Therefore, controlled studies are necessary to elucidate the place of NST in the therapy of high-risk acute leukemias.
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