TABLE 1.
Protein | Study | No. of patients in the study | Association direction | Diagnosis timepoint (median day post-HCT) | Prognostic timepoint (median day post-HCT) | References |
Plasma aGVHD | ||||||
4 biomarker panel: IL-2-receptor-α, hepatocyte growth factor (HGF), IL-8 tumor necrosis factor receptor-1 | Paczesny 2009 | 42+282†+142† | Increased | 28 | ND | 52 |
Interleukin-6 (IL-6) | McDonald 2015 | 74†+76 † | Increased | 28 | Not significant | 53 |
Kennedy 2014 | 53 | Increased (3–14), then decreased | 30 | 7–14 | 54 | |
Stimulation 2 (ST2) | Vander Lugt 2013 | 20+381†+673*+75* | Increased | 28 | 14 | 55 |
Levine 2015 | 328+164†+300† | Increased | 28 | ND | 56 | |
Abu Zaid 2017 | 211 patients (independent cohort post-validation) | Increased | 28 | ND | 58 | |
McDonald 2015 | 74†+76† | Increased | 28 | Not significant | 53 | |
Hartwell 2017 | 620+309†+358† | Increased | ND | 7 | 59 | |
Major-Monfried 2018 | 236+142†129† | Increased | ND | 7 | 64 | |
McDonald 2017 | 165 | Increased | ND | 14 | 65 | |
T cell immunoglobulin domain and mucin domain (TIM3) | McDonald 2015 | 74†+76†+167* | Increased | 28 | 14 | 53 |
Abu Zaid 2017 | 211 patients (independent cohort post-validation) | Increased | 28 | ND | 58 | |
AREG/EGF ratio | Holtan 2016 | 105+50† | Increased | 160 | ND | 66 |
Skin specific | ||||||
Elafin | Paczesny 2010 | 522+492† | Increased | 28 | ND | 67 |
Bruggen 2015 | 59 | Increased | 28 | ND | 68 | |
Liver specific | ||||||
REG3 α, HGF, and Keratin 18 (KRT18) | Harris 2012 | 954, 3 centers | Increased | 14 | 28 | 69 |
GI specific | ||||||
Regenerating islet-derived 3-α (REG3 α) | Ferrara 2011 | 20+871†143† | Increased | 28 | ND | 71 |
T cell immunoglobulin domain and mucin domain (TIM3) | Hansen 2013 | 20+127†+22† | Increased | 28 | ND | 73 |
Cellular aGVHD | ||||||
Regulatory T cells | Magenau 2010 | 215 | Decreased | 3–14 | 28 | 19 |
CD146+ T cells | Li 2016 | 20+214† | Increased | ND | 14 | 28 |
CD30 | Chen 2012 | 53 | Increased | ND | ND | 80 |
Chen 2017 | 34 | Increased | ND | NA | 81 | |
Invariant natural killer T cells (iNKT) | Chaidos 2012 | 57 | Increased | ND | NA | 82 |
Plasma chronic GVHD | ||||||
sBAFF | Sarantopoulos 2007 | 104 | Increased | 480 | NA | 93 |
Fujii 2008 | 80 | Increased | 171 (early&), 429 (late&) | NA | 94 | |
Kitko 2014 | 35+109†+211† | Increased, and not validated in independent cohort | 154+, 256 (early&), 619 (late&) | NA | 95 | |
Kariminia 2016 | 23+198†+83† | Increased | 203,174 | NA | 96 | |
Saliba 2017 | 341 | Increased/decreased # | 189 | NA | 98 | |
CXCL9 | Kitko 2014 | 35+109†+211† | Increased | 154+, 256 (early&), 619 (late&) | NA | 95 |
Yu 2016 | 53+211†+180† | Increased | 210+,203& | 100 | 99 | |
Kariminia 2016 | 23+198†+83† | Increased, and not validated in independent cohort | 203+,174& | NA | 96 | |
Hakim 2016 | 26+83† | Increased | 132 | NA | 42 | |
Abu 2017 | 211 | Increased | NA | 100, 180, 365 (time dependent analysis) | 58 | |
CXCL10 | Kariminia 2016 | 23+198†+83† | Increased | 203+,174& | NA | 96 |
Hakim 2016 | 26+83† | Increased | 132 | NA | 42 | |
Ahmed 2016 | 78+37 | Increased | 132 | NA | 97 | |
Four protein panel (CXCL9, ST2, OPN, MMP3) | Yu 2016 | 53+211†+180† | Increased | 210,203 | 100 | 99 |
MMP3 | Liu 2016 | 76 (BOS) | Increased | 531 | NA | 100 |
CCL15 | Du 2018 | 211†+792† | Increased at onset, but not prognostic | 203 | 100 | 101 |
Cellular chronic GVHD | ||||||
CD163 | Inamoto 2017 | 40+127† | Increased | NA | 80 | 102 |
B cells | ||||||
TLR9+ | She 2007 | 54 | Increased | 171 (early), 429 (late) | NA | 103 |
CD21low | Greinix 2008 | 70 | Increased | 1428 | NA | 104 |
Kuzmina 2013 | 136 | Increased | 143 | NA | 105 | |
BAFF/B cell ratio | Sarantopoulos 2009 | 57 | Increased | 180 | NA | 23 |
Tregs | Zorn 2005 | 57 | Decreased | 720 | NA | 20 |
CD4+CD146+CCR5+ | Forcade 2017 | 40 | Increased | 942 | NA | 29 |
TFH | Forcade 2016 | 66 | Decreased | 867 | NA | 25 |
ND, not done; NA, not applicable; †Patient number in validation cohort 1 and cohort 2; +cohort 1 and &cohort 2.