Diagnostic and Prognostic Role of Fecal Calprotectin As a Biomarker for Gastrointestinal Graft Versus Host Disease: A Systematic Review of Literature
Authors: Rafae Abdul , Malik Mustafa Nadeem , Khan Ali Younas , Qureshi Anum , Abu Zar Muhammad , Durer Ceren , Durer Seren , Kamal Ahmad , Selene Insija Ilyas , Jose Jemin Aby , Khalil Muhammad Jahanzeb , Fazeel Hafiz Muhammad , Usman Muhammad , Ijaz Awais , Anwer Faiz 
Published: October 2019

Abstract
Introduction:
Graft versus host disease (GVHD) is the most significant complication after allogeneic hematopoietic stem cell transplantation (HSCT) and a leading cause of morbidity and mortality. The incidence of acute gastrointestinal graft versus host disease (GI-GVHD) in HSCT patients is reported between 40% to 50%. Fecal calprotectin (FC) has an established role as a diagnostic modality and a biomarker of disease activity in patients with inflammatory bowel disease (IBD). It has been suggested that FC may also play an important role in diagnosing and assessing the severity of GVHD and in determining resistance and response to corticosteroid treatment.
Methods:
To study the diagnostic and prognostic role of FC in GVHD patients, we performed a systematic review, 19 articles published after 2004 were selected from following four databases (PubMed, Embase, Cochrane Library and Web of Science). Numeric data were summarized using means, medians, and ranges. Categorical data were summarized using absolute values and percentages.
Results:
A total of 494 patients were included. Two hundred fifty two patients (51%) developed acute GVHD. Hundred seventy nine patients (71%) had GI-GVHD and 73 patients (29%) had non GI-GVHD. In one of the cohorts (n=21), median FC (mFC) levels were 198.9 mg/kg [range(r) =58.4-500] in patients with GVHD versus 32.2 mg/kg (r=15.6-89) in patients without GVHD (p=0.0005). In a similar cohort (n=23), mFC levels were 504 mg/kg in patients with GVHD and 107.4 mg/kg in patients without GVHD (p=<0.001). Five cohorts compared mFC level in GI-GVHD vs. non GI-GVHD patients and the results were as follows: 318 mg/kg (r=36-596) vs. 38 mg/kg (r=35.5-56), p=0.003 (61 patients); 595 mg/kg vs. 51.7 mg/kg, p=<0.001 (64 patients); 396.6 mg/kg (r=142.1-500) vs. 115.2 mg/kg (r=58.4-292.3), p=0.02 (14 patients); 500 mg/kg vs. 95 mg/kg , p=0.0229; 56 mg/kg vs. 121 mg/kg, p=0.67 (31 patients). In another cohort (n=40), mFC level was 193.9 mg/kg in patients with GI-GVHD as compared to mFC level of 53.1 mg/kg in patients with CMV colitis (p=0.017). In another cohort (n=14), mFC level was 134.9 mg/kg (r=58.4-292.3) in patients with grade I-II GVHD as compared to mFC level of 396.6 mg/kg (95.2-500) in patients with grade III-IV GVHD (p=0.029). In another cohort (n=54) with GI-GVHD, corticosteroids responsive patients had mFC level of 64 mg/kg (range 17-360) at onset and 49 mg/kg (range 12-238) at 1 week of treatment while corticosteroid resistant patients had mFC level of 488 mg/kg (range 65-835) at onset and 542 mg/kg (range 121-1080) at 1 week of treatment (p=0.028 at onset and p=0.038 at one week). In another cohort (n=7), mean FC level was 24 mg/kg (r=16-31) in steroid responsive patients as compared to mean FC level of 449 mg/kg (r=116-1111) in steroid resistant patients (p=0.032).
Conclusions:
Our analysis demonstrates that FC levels are higher in patients with GI-GVHD. Furthermore, a linear correlation is present between FC levels and severity of GVHD. FC levels are higher in patients with steroid-resistant GVHD and can be useful to determine treatment response. Data on FC levels in these patients seem promising and future randomized prospective trials are needed.

Disclosures
No relevant conflicts of interest to declare.