Glucagon-like peptide-1 (GLP-1) may serve as a predictive biomarker of inflammation in patients undergoing high-dose chemotherapy and autologous stem cell transplantation (ASCT), according to research published in Biology of Blood and Marrow Transplantation.
Adverse effects of ASCT can include veno-occlusive disease of the liver, interstitial pneumonia syndrome, and graft failure, among others; these side effects might be exacerbated by chemotherapy-induced mucositis that could result in bacterial translocation and systemic inflammation.
Because gastrointestinal damage could be an early event precipitating mucositis and other adverse effects, researchers assessed whether markers of intestinal barrier damage were early predictive biomarkers of toxicity. Specifically, they examined plasma levels of GLP-1, which has been found to promote intestinal growth and repair in animal studies.
In this study, researchers prospectively examined fasting plasma levels of GLP-1 in 66 adult patients (age range, 20-72 years) undergoing chemotherapy and ASCT for lymphoma and multiple myeloma at a hospital in Denmark. Levels of the inflammatory marker C-reactive protein (CRP) were regularly monitored as well.
Levels of GLP-1 increased significantly following chemotherapy and reached maximum levels 7 days after transplant. Before conditioning, the median level of GLP-1 was 8 pmol/L (interquartile rage [IQR], 4-12), compared with 10 pmol/L (IQR, 6-17) at 7 days post-transplant (P =.007). The magnitude of GLP-1 increase was associated with the intensity of the conditioning regimen that patients underwent.
Of the 48 patients in whom day 0 CRP levels were available, 44 (92%) had CRP levels within the normal range of 10 mg/L or less. Median CRP increased post-transplantation and reached a maximum 9 days after ASCT. From day 2 post-transplantation onward, daily median levels of CRP were significantly higher than at day 0 (all P <.0017).
GLP-1 levels at day 0 were positively associated with both CRP levels (46 mg/L increase per doubling of GLP-1; P =.00018) and increased number of days with fever (32% increase per doubling of GLP-1; P =.0058).
Patients whose GLP-1 levels were higher than the median at day 0 experienced significantly higher CRP levels from day 3 to day 10 post-transplantation and had a peak value of 238 mg/L, compared with patients with lower GLP-1 levels (P ≤.041) who had a peak value of 129 mg/L.
The authors concluded that these results showed a relationship between fasting GLP-1 and high-dose chemotherapy and also supported a role for GLP-1 in mucosal health. Moreover, baseline levels of GLP-1 might predict subsequent systemic inflammation.
1. Ebbesen MS, Kissow H, Hartmann B, et al. Glucagon-like peptide-1 is a marker of systemic inflammation in patients treated with high-dose chemotherapy and autologous stem cell transplantation [published online February 4, 2019]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2019.01.036