• Gandhi, Parth
• Hoeschen, Andrea
• Rashidi, Armin
• Khoruts, Alexander
• Gandhi, Isha
• Macmillan, Margaret L.
• Weisdorf, Daniel J.
• Blazar, Bruce R.
• Betts, Brian C.
• Mosher, Wes
• Cao, Qing
• Jurdi, Najla H. El
• Panoskaltsis-Mortari, Angela
• Holtan, Shernan G.
• Chen, Chi

Abstract

Minnesota High Risk and steroid-refractory acute graft-versus-host disease (aGVHD) are life-threatening complications of allogeneic hematopoietic cell transplantation (HCT). Recent data suggests dysbiosis may relate to GVHD outcomes. Bacteria in the lower gastrointestinal tract (LGI) produce short chain fatty acids (SCFAs) as fuel for enterocytes and modulators of mucosal immunity. LGI damage caused by aGVHD and antibiotic administration may be detrimental to SCFAs production and thus intestinal repair. However, limited data exists on how plasma SCFA levels vary between aGVHD patients who respond to treatment and those who do not. This study examined how aGVHD treatment response relates to plasma levels of five common SCFAs: acetate, propionate, butyrate, isovalerate, and valerate.</jats:p><jats:p>Patients and Methods</jats:p><jats:p>Serial plasma samples (n=221) were collected from 49 patients who underwent treatment for Minnesota High Risk or steroid-dependent/refractory aGVHD on NCT02525029 at study baseline and at 7, 14, 28 and 56 days post-treatment initiation. GVHD severity was graded using Minnesota criteria. Patients were categorized by their response to therapy at day 28 (complete/partial response [CR/PR], n=35 versus no response or death [NR], n=14). Plasma SCFA levels were quantified via liquid chromatography and cytokines measured by multiplex cytokine array. Changes in SCFA over time were assessed by repeated measures ANOVA. SCFA levels responders versus non-responders at individual time points were compared using Mann-Whitney testing and principal component analysis (PCA). SCFA, cytokines, and GVHD biomarkers including ST2, REG3a, and AREG were correlated using Spearman's rho with Bonferroni correction for multiple comparisons.</jats:p>

Topics

• refractory
• liquid chromatography