Fecal Calprotectin as a Diagnostic and Prognostic Biomarker for Gastrointestinal Graft Versus Host Disease: A Systematic Review of Literature

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.

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Chronic graft-versus-host disease presenting as acute polymyositis: A case series and systematic review

Transplant Immunology ◽

10.1016/j.trim.2021.101520 ◽

2021 ◽

pp. 101520

Author(s):

Moazzam Shahzad ◽

Sibgha Gull Chaudhary ◽

Abdul Basit ◽

Connor Thellman ◽

Liza Rodriguez ◽

...

Keyword(s):

Systematic Review ◽

Graft Versus Host Disease ◽

Case Series ◽

Host Disease ◽

Graft Versus Host

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Extracorporeal photopheresis for chronic graft-versus-host disease: a systematic review and meta-analysis

Blood Research ◽

10.5045/br.2014.49.2.100 ◽

2014 ◽

Vol 49 (2) ◽

pp. 100 ◽

Cited By ~ 25

Author(s):

Mohsin Ilyas Malik ◽

Mark Litzow ◽

William Hogan ◽

Mrinal Patnaik ◽

Mohammad Hassan Murad ◽

...

Keyword(s):

Systematic Review ◽

Graft Versus Host Disease ◽

Meta Analysis ◽

Extracorporeal Photopheresis ◽

Host Disease ◽

Graft Versus Host

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Adverse events in second- and third-line treatments for acute and chronic graft-versus-host disease: systematic review

Therapeutic Advances in Hematology ◽

10.1177/2040620720977039 ◽

2020 ◽

Vol 11 ◽

pp. 204062072097703

Author(s):

Vladica M. Velickovic ◽

Emily McIlwaine ◽

Rongrong Zhang ◽

Tim Spelman

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Graft Versus Host Disease ◽

Chronic Gvhd ◽

Hematopoietic Stem ◽

Host Disease ◽

Pharmaceutical Management ◽

Graft Versus Host ◽

Increased Risk ◽

Third Line

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of graft- versus-host disease (GvHD), a strong prognostic predictor of early mortality within the first 2 years following allo-HSCT. The objective of this study was to describe the harm outcomes reported among patients receiving second- and third-line treatment as part of the management for GvHD via a systematic literature review. Methods: A total of 34 studies met the systematic review inclusion criteria, reporting adverse events (AEs) across 12 different second- and third-line therapies. Results: A total of 14 studies reported AEs across nine different therapies used in the treatment of acute GvHD (aGvHD), 17 studies reported AEs of eight different treatments for chronic GvHD (cGvHD) and 3 reported a mixed population. Infections were the AE reported most widely, followed by haematologic events and laboratory abnormalities. Reported infections per patient were lower under extracorporeal photopheresis (ECP) for aGvHD (0.267 infections per patient over 6 months) relative to any of the therapies studied (ranging from 0.853 infections per patient per 6 months under etanercept up to 1.998 infections per patient on inolimomab). Conclusion: The reported incidence of infectious AEs in aGvHD and grade 3–5 AEs in cGvHD was lower on ECP compared with pharmaceutical management.

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Preclinical Studies of MSC-Derived Extracellular Vesicles to Treat or Prevent Graft Versus Host Disease: a Systematic Review of the Literature

Stem Cell Reviews and Reports ◽

10.1007/s12015-020-10058-x ◽

2020 ◽

Author(s):

Manika Gupta ◽

Alvin Tieu ◽

Mitchell Slobodian ◽

Risa Shorr ◽

Dylan Burger ◽

...

Keyword(s):

Systematic Review ◽

Extracellular Vesicles ◽

Graft Versus Host Disease ◽

Preclinical Studies ◽

Review Of The Literature ◽

Host Disease ◽

Graft Versus Host

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Management of oral Graft versus Host Disease with topical agents: A systematic review

Medicina Oral Patología Oral y Cirugia Bucal ◽

10.4317/medoral.20968 ◽

2016 ◽

pp. e72-e81 ◽

Cited By ~ 6

Author(s):

R Albuquerque ◽

Z Khan ◽

A Poveda ◽

J Higham ◽

A Richards ◽

...

Keyword(s):

Systematic Review ◽

Graft Versus Host Disease ◽

Host Disease ◽

Graft Versus Host

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Effectiveness of immunosuppression minimisation, conversion or withdrawal strategies in paediatric solid organ and haematopoietic stem cell transplantation: a protocol of a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-037721 ◽

2020 ◽

Vol 10 (12) ◽

pp. e037721

Author(s):

Carlos Martin Saborido ◽

Alberto M Borobia ◽

Javier Cobas ◽

Lorenzo D'Antiga ◽

Esteban Frauca ◽

...

Keyword(s):

Quality Of Life ◽

Systematic Review ◽

Blood Pressure ◽

Clinical Trials ◽

Graft Versus Host Disease ◽

Graft Rejection ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

IntroductionPaediatric transplantation is the only curative therapeutic procedure for several end-stage rare diseases affecting different organs and body systems, causing altogether great impact in European children’s health and quality of life. Transplanted children shift their primary disease to a chronic condition of immunosuppression to avoid rejection. Longer life expectancy in children poses a greater risk of prolonged and severe side effects related to long-term immunosuppressive (IS) disabilities and secondary cancer susceptibility. The goal remains to find the best combination of IS agents that optimises allograft survival by preventing acute rejection while limiting drug toxicities. This systematic review will aim to determine the optimal IS strategy within the so-called minimisation, conversion or withdrawal strategies.Methods and analysisWe will search the following databases with no language restrictions: Cochrane Central Register of Controlled Trials in the Cochrane Library, OvidSP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; OvidSP Embase Classic+Embase; Ebsco CINAHL Plus, complete database; WHO International Clinical Trials Registry Platform search portal. We will include controlled and uncontrolled clinical trials along with any prospective or retrospective study that includes a universal cohort (all participants from a centre/region/city over a certain period). Cases series and cross-sectional studies are excluded. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. The outcomes included in this review are: patient survival, acute graft rejection, chronic graft rejection, diabetes, graft function, graft loss, chronic graft versus host disease, acute graft versus host disease, surgical complications, infusion complications, post-transplant lymphoproliferative disease, liver function, renal function, cognition, depression, health-related quality of life, hospitalisation, high blood pressure, low blood pressure, cancer—other, cancer—skin, cardiovascular disease, bacterial infection, Epstein-Barr infection, cytomegalovirus infection, other viral infections and growth.

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