Plasma biomarkers of lower gastrointestinal and liver acute GVHD

Abstract

The lower gastrointestinal tract (LGI) and liver are the GVHD target organs most associated with treatment failure and nonrelapse mortality. We recently identified regenerating islet-derived 3-␣ (REG3␣) as a plasma biomarker of LGI GVHD. We compared REG3␣ with 2 previously reported GI and liver GVHD diagnostic biomarkers, hepatocyte growth factor (HGF) and cytokeratin fragment 18, in 954 hematopoietic cell transplantation patients. All 3 biomarkers were significantly elevated in LGI GVHD compared with non-GVHD diarrhea; REG3␣ discerned LGI GVHD from non-GVHD diarrhea better than HGF and cytokeratin fragment 18. Although all 3 biomarkers predicted nonresponse to therapy at day 28 in LGI GVHD patients, only REG3␣ and HGF concentrations predicted 1-year nonrelapse mortality (P ‫؍‬ .01 and P ‫؍‬ .02, respectively). Liver GVHD without GI involvement at GVHD onset and non-GVHD liver complications were uncommon; all 3 biomarkers were elevated in liver GVHD, but did not distinguish GVHD from other causes of hyperbilirubinemia. (Blood. 2012;119(12): 2960-2963)

Allogeneic hematopoietic SCT for adults AML using i.v. BU in the conditioning regimen: outcomes and risk factors for the occurrence of hepatic sinusoidal obstructive syndrome

“…This was also suggested in other studies. [21][22][23][40][41][42] Acute GVHD is related in part to tissue injury and cytokine release, 43,44 and limitation of tissue injury with this regimen may have contributed to this observation. However, severe acute GVHD remains a major obstacle to transplant success and better methods for GVHD prevention with preservation of antileukemic effects need to be explored.…”

High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation

“…The ultimate aim of these studies is to ameliorate severe GVHD and further improve survival in CBT recipients. (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) …”

“…The biomarkers interleukin2 receptor a (IL2Ra), tumor necrosis factor receptor 1 (TNFR1), hepatocyte growth factor (HGF), interleukin-8 (IL-8), elafin, and regenerating islet-derived protein 3-a (REG3a) are associated with the diagnosis of aGVHD and are significantly associated with the subsequent risk of day 180 TRM in unmodified allograft recipients. [8][9][10][11][12] Furthermore, levels of the biomarker suppressor of tumorigenicity 2 (ST2) obtained at the time of onset of aGVHD are associated with the risk of treatment-resistant aGVHD and 6-month TRM after aGVHD onset independent of aGVHD clinical grade. 13 Whether GVHD biomarkers are informative in CBT recipients has not been investigated, and such biomarkers could have significant clinical utility.…”

18F-FDG PET/CT for the assessment of gastrointestinal GVHD: results of a pilot study

“…1 Of note, severe acute gastrointestinal GVHD (GI-GVHD) occurring early after allo-SCT is likely the most serious complication and is a major determinant of long-term survival. 2,3 The gold standard method for the diagnosis of GI-GVHD remains based on clinical symptoms. 4 The current procedure to confirm GI-GVHD is based on endoscopic examination and histology, mainly to exclude differential diagnosis.…”