Using multivariate techniques, we studied the relationships of cytotoxic regimen, intestinal mucosal damage, and fungal colonization in the pathogenesis of invasive fungal disease in 138 patients undergoing induction therapy for untreated acute myeloid leukemia (AML) according to three institutional protocols: AML-84 (cytarabine/daunorubicin), AML-87 (high-dose cytarabine/etoposide/daunorubicin), and AML-88 (mitoxantrone/etoposide). Invasive fungal disease occurred in 36%, 6%, and 2.6% of patients participating in protocols AML-87, AML-84, and AML-88, respectively (chi 2 = 23.465; P < .0001). Protocol AML-87 was the strongest independent predictor in the multivariate model (RR = 26.7; P < .0001). Cytotoxic therapy-related epithelial damage in the gut, as measured by D-xylose malabsorption, correlated with invasive fungal disease and protocol AML-87. Fungal colonization, a predictor of invasive fungal disease, correlated with frequent modifications of antibiotic regimens. These results demonstrate the role of cytotoxic regimen-related gut epithelial damage, antibiotic-prescribing behavior, and fungal colonization in the pathogenesis of invasive fungal disease in patients with leukemia.

Serial D-xylose absorption studies in subjects with AML produced a characteristic profile of cytotoxic therapy-related damage to the functional integrity of the intestinal epithelium that was regimen dependent, myelosuppression independent, and predictive for invasive infectious complications. Further study to validate these observations appears warranted.

An open, nonrandomized, phase 2 study of 53 adult patients who had 60 neutropenic episodes was conducted to determine if quinolone antibacterial prophylaxis could reduce the need during febrile episodes for parenteral therapy directed at gram-negative organisms. Suspected infections among recipients of quinolones were treated empirically with vancomycin and ceftazidime; therapy with the latter was discontinued after 24-48 hours in the absence of infection due to gram-negative organisms. In five neutropenic episodes, patients had no fever or infection. An aerobic gram-negative bacillus was isolated during only 1 (1.8%) of 55 febrile episodes. Febrile episodes occurred at a median of day 15 of cytotoxic therapy. Vancomycin monotherapy was successful in 22 (50%) of 44 evaluable cases. Modification of the vancomycin regimen by the addition of metronidazole or rifampin increased the response rate to 40 (91%) of 44. Response occurred after a median of 4.5 days. Parenteral empirical therapy with amphotericin B was required in only 3 (7%) of 44 cases. The study strategy safely permitted a reduction in the amount and duration of antibiotic therapy directed against gram-negative organisms in febrile neutropenic patients.

The histopathology and clinical presentation of 19 cases of primary gastrointestinal lymphoma is described. Our patients are similar to others in the Middle East but have a lower incidence of diarrhoea and malabsorption. All revealed a widespread chronic inflammatory background. Four patients with primary gastric lymphoma had endoscopic biopsies from the duodenum; these biopsies were completely free from tumour but showed a moderate to severe diffuse lymphoplasmacytic infiltrate. Electron microscopy shows that tumour cells penetrate basement membranes and invade the epithelium which becomes thin and attenuated. Substances which inhibit lymphocyte tropism might be useful in preventing intestinal ulceration. The MALT concept has been found useful in classification of the tumours. Two patients with unusual mesenteric node histology are described and it is thought that the appearances may indicate a substantial capacity for differentiation in the group of tumours.