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

Area of Science:

• Gastroenterology
• Oncology
• Pharmacology

Background:

• Cytotoxic chemotherapy for acute myeloid leukaemia (AML) can damage the intestinal mucosa.
• Intestinal barrier dysfunction is linked to chemotherapy-related toxicities and infections.
• Lisofylline was investigated for its potential to mitigate these effects.

Purpose of the Study:

• To prospectively evaluate intestinal barrier function during AML chemotherapy.
• To correlate objective measures of gut permeability with clinical toxicities and infection rates.
• To assess the efficacy and safety of lisofylline in reducing chemotherapy-induced intestinal damage.

Main Methods:

• A clinical trial involving adult AML patients receiving idarubicin plus cytarabine.
• Weekly measurements of D-Xylose absorption and lactulose:mannitol ratio to assess intestinal permeability.
• Correlation of permeability markers with non-haematologic toxicities (nausea, vomiting, diarrhoea, stomatitis) and infection rates.

Main Results:

• Intestinal permeability increased significantly in the first few weeks of chemotherapy, then recovered.
• Increased gut permeability correlated with higher rates of infection, nausea, vomiting, and diarrhoea.
• Lisofylline treatment was associated with increased intestinal permeability and infection-related morbidity, despite reduced neutropenia duration.

Conclusions:

• Objective measures of intestinal barrier function (D-Xylose, lactulose:mannitol ratio) are valuable surrogates for chemotherapy-induced mucosal damage.
• These permeability markers correlate well with clinical outcomes like infection and toxicity.
• Lisofylline did not demonstrate efficacy in reducing chemotherapy-related intestinal morbidity in this trial, highlighting the need for effective interventions.