The Relation and Value Of Endoscopy Biopsy In Different Sites For The Diagnosis Of Lower and Upper intestinal Graft-Versus-Host Disease
Authors: Rodrigues Morgani , de Macedo Costa Erika Maria , Almeida Alessandro deMoura , de Assis Reijane Alves , Cardoso Santos Fernanda Nazare , Oliveira Erika Abdon , Pasqualin Denise dacunha , P. S Bezerra Alanna Mara , Esteves Iracema , Nunes Barroso Karine Sampaio , Kerbauy Fabio R. , Kutner Jose Mauro , Feitosa Ribeiro Andreza Alice , Sobrinho Jairo , Torres Margareth Afonso , Hamerschlak Nelson 
Published: October 2019

Abstract

Introduction
Graft-versus-host disease (GvHD) causes morbidity and mortality in recipients of allogeneic hematopoietic stem cell transplantation (ASCT). This study assessed the distribution of GvHD in gastrointestinal (GI) biopsies from the upper and lower GI tract in all patients who had undergone ASCT in our institution between 2005 to 2013 and evaluated the correlation between biopsy of upper and lower GI, possible relation with CMV Infection in GI biopsy and Blood sample, GvHD GI grade and extra-intestinal manifestations of GvHD

Methods
We performed a retrospective pathology records review for all patients diagnosed with positive GI GvHD biopsy, who underwent both upper and lower endoscopy. We also reviewed pathology and clinical reports to determine which biopsy sites were diagnostic of GvHD and to evaluate for the possible presence of extra-intestinal manifestations GvHD at the time of biopsy, CMV Status on the biopsy findings and blood sample.

Results
One hundred eighty nine patients (78 children and 111 adults) received ASCT transplant between 2005 to 2013. Twenty eight patients ( 14,8%) had undergone both upper and lower positive biopsy for acute GvHD diagnosis. Seventeen ( 60,7%) were male. The median age was 28 (1.50- 63.6) years old. Eleven patients had AML (39%), 6 had benign diseases (21.4%); five had ALL (17.9%); 2 lymphomas; 02 (7.1%) CML and 01 (3.1%) MDS. Main stem cell source was bone marrow 14 (50%), followed by PSCB in 7 (25%) and SCUP in 7 (25%). ATG was used in 16 (57, 1%) patients. Extra- intestinal manifestation of GVHD was: skin in 19 (67, 9%); liver in 6 (21,4%) patients. Five (17,9%) had the 3 organ involvement. The GI GvHD grade was: grade I in 7 ( 25%) , grade II in 4 ( 14,3%), grade III in 9 ( 32.1% ) and grade IV in 8 ( 28,6%). Regarding the concordance between the biopsy findings, there is agreement only between Ileum Biopsy Negative plus ileum and Rectum, because both have a higher percentage of positive GvHD. The stomach has a higher percentage of negative GvHD, and therefore there is no agreement with Colon plus ileum and Rectum. The frequency and correlation between involvement of different parts of GI-GVHD are presented in Tables 1,2 and 3. Just 2 ( 11.1%) patients had negative rectal biopsy and positive colon + ileum. Nine (32, 1%) had blood CMV detected. Five ( 17.9%) had positive Biopsy for CMV ( one in stomach, 3 in Colum and on in rectum), and just one patients had both positive.
There is no association between clinical grade of GI-GVHD and the presence of CMV in biopsy and blood (CMV positive X GvHD grade, p=0.885; and biopsy CMV positive X GvHD grade, p= 0.859).
It has no association between clinical grade of GI- GVHD and conditioning (p= 0.070) and use of ATG (p=0.867). HLA disparity was related with higher grades of GI-GVHD (p=0.029). All patients with Grade I are Fullmatch, whereas patients with Grade III and IV had highest percentage of mismatch [grade III= 5 (55.6%); and grade IV= 4 (57.15%) patients].
The median follow up was 7.2 (1.8-90.6) month. Overall survival (OS) was 40% in 60 month and patients with grade IV GVHD had worst OS ( P= 0.004).

Conclusion
Use of sigmoid biopsy for GvHD diagnosis is effective, safe, and less expensive compared to other endoscopic interventions, because it was most frequent site of lower GI-GVHD and only 11% of biopsies were discordant. CMV infection may be underdiagnosted with this approach, where colonocospy study should be considered as most of CMV positivity in biopsy was in Colum.

Disclosures:
No relevant conflicts of interest to declare.