Intestinal mucosal dysfunction and infection during remission-induction therapy for acute myeloid leukaemia

Abstract

Intestinal barrier function was prospectively examined in the course of a clinical trial evaluating the efficacy and safety of lisofylline for reducing cytotoxic therapy-induced intestinal epithelial damage-related infectious morbidity in patients receiving standard remission-induction therapy for acute myeloid leukaemia. The absorption and permeation of oral D-Xylose, lactulose and mannitol were measured weekly from baseline until marrow recovery in adult recipients of idarubicin plus cytarabine for untreated acute myeloid leukaemia. These studies were correlated with non-haematologic chemotherapyrelated toxicities reflecting mucosal damage, including nausea, vomiting, stomatitis, diarrhoea, abdominal pain and systemic infection. D-xylose absorption decreased and lactulose:mannitol ratio reflecting intestinal permeability increased from baseline until the second and third week after the beginning of the treatment followed by recovery. These measures correlated with infection rates, nausea, vomiting, diarrhoea and increased blood product utilization. Lisofylline was associated with increased intestinal permeability, nausea, vomiting and infection-related morbidity despite a reduction in the duration of neutropaenia. These surrogates of intestinal barrier function correlated well with clinically important outcomes despite the failure to demonstrate reduced morbidity with lisofylline and represent useful objective outcome measurements for future clinical trials of products for the amelioration of the effects of cytotoxic therapy on the intestinal mucosa.

Ciprofloxacin versus colistin prophylaxis during neutropenia in acute myeloid leukemia: two parallel patient cohorts treated in a single center

“…Both factors are potential ports of entry for bacterial invasion into the bloodstream and have been described previously. 4 However, only mucositis emerged as an independent predictor of a higher infection rate, particularly in patients receiving consolidation therapies.…”

“…In addition to disease-and therapy-induced myelosuppression, disease-related conditions, such as alteration of the host defenses secondary to infiltration of the bone marrow and therapy-induced side effects (such as mucositis or diarrhea after breakdown of the mucosal barrier), further contribute to the high risk of infections. 4 Fluoroquinolone has partially replaced the previous use of non-absorbable antibiotics, such as colistin/polymyxin B and oral vancomycin, for the prophylaxis of neutropenia-related infections. Initially, this was based on better tolerance for fluoroquinolone rather than on a proven decrease in the infection rate.…”

Changes in Intestinal Permeability and Nutritional Status After Cytotoxic Therapy in Patients with Cancer

“…Based on data from previous studies (28), we expected that the patient group would have an increase of 0.029 in the L/M ratio after cytotoxic therapy. Using a power of 80% and a 2-sided significance level of 5%, a sample size of 16 was considered adequate to detect a difference in the L/M ratio after cytotoxic therapy.…”

The Diagnostic Approach to the Febrile Neutropenic Patient: Clinical Considerations

“…The nadir of cytotoxic therapy-induced myelosuppression typically occurs at the end of the second week, between day 10 and 14, from the fi rst day of cytotoxic therapy [ 21 ]. This is, coincidentally, the time of the maximum cytotoxic effect of the anticancer chemotherapies on the intestinal mucosa [ 20 , 21 , 65 ] and the time of maximal oral and gastrointestinal mucositis [ 9 , 11 , 21 , 85 , 93 , 95 ].…”