Table 5.

Plasma Biomarkers for Chronic GVHD

Name	Study	(n)	Associations/Timepoints in cGVHD (D0 = HCT date)	Framework steps completed	Potential clinical implementation	Ref
Diagnostic Biomarkers
sBAFF	Sarantopoulos 2007	104	Increased levels in active cGVHD	Step 1: Discovery	• Improve diagnostic accuracy • Differentiate GVHD vs other complications	39
	Ahmed 2015	115	Increased levels at 6 and 12 months	Step 1: Previous discovery		41
	Kariminia 2016	283	Increased levels around time of diagnosis	Step 1: Previous discovery Step 2: 2 cohorts		42
	Rozmus 2019	107	Increased levels around onset of symptoms	Step 1: Previous discovery		43
CXCL9	Kitko 2014	320	Increased levels at diagnosis	Step 1: Discovery Step 2: 2 cohorts		44
	Kariminia 2016	85	Increased levels in 1 replication cohort	Step 1: Previous discovery Step 2: 2 cohorts		42
	Hakim 2016	95	Increased levels and upregulation of gene expression	Step 1: Previous discovery		45
CXCL10	Ahmed 2015	115	Increased levels at 6 and 12 months	Step 1: Hypothesis		41
	Kariminia 2016	283	Increased levels in both replication cohorts	Step 1: Previous discovery Step 2: 2 cohorts		43
	Hakim 2016	95	Increased levels and upregulation of gene expression	Step 1: Hypothesis		45
Biomarker panel: ST2, MMP3, CXCL9, OPN	Yu 2016	172	Increased levels at diagnosis	Step 1: Discovery Step 2: 2 cohorts		47
MMP3	Liu 2016	112	Increased levels in BOS patients	Step 1: Discovery		48
DKK3	Inamoto 2020	186	Increased levels at diagnosis	Step 1: Discovery		50
Reg3α	DePriest 2021	289	Increased levels associated with GI-cGVHD	Step 1: Previous discovery Step 2: 2 cohorts		51
Predictive Biomarkers
No validated cGVHD predictive biomarker exists					• Intensify for high risk group • Reduce immunosuppression for low/standard risk group
Response Biomarkers
sBAFF	Whittle 2011	46	Increased levels 1 month after ECP predicted response of cutaneous cGVHD	Step 1: Previous discovery	• Monitoring treatment response • Guide GVHD management • Future: Clinical efficacy endpoint	58
ST2	Dunavin 2018	16	ST2 levels declined after 2-, 4- and 6-months of ECP	Step 1: Previous discovery		57
Prognostic Biomarkers
CXCL9	Giesen 2020	480	Increased levels at symptom onset associated with severe cGVHD	Step 1: Previous discovery	• Anticipate course of disease • Adjust immunosuppression	60
DKK3	Inamoto 2020	186	Increased levels at diagnosis associated with NRM	Step 1: Discovery		50
MMP-9	Inamoto 2021	33	Increased levels at BOS diagnosis associated with OS	Step 1: Discovery		61
Reg3α	DePriest 2021	289	Increased levels at GI-cGVHD diagnosis associated with nrm	Step 1: Previous discovery Step 2: 2 cohorts		51
Risk Biomarkers
Biomarker panel: ST2, MMP3, CXCL9, OPN	Yu 2016	172	Levels D+100 associated with cGVHD development	Step 1: Discovery Step 2: 2 cohorts	• Implement preemptive strategies	47
CXCL9	Abu Zaid 2017	211	Increased levels D+100 or D+180 associated with cGVHD development	Step 1: Previous discovery Step 2: Clinical trial cohorts		26
	Dai 2021	287	Increased levels D+28 associated with severe cGVHD development	Step 1: Previous discovery		64
CD163	Inamoto 2017	167	Increased levels D+80 associated with de-novo cGVHD	Step 1: Previous discovery		66