Complex endoscopic diagnosis of the gastrointestinal form of acute graft-versus-host disease in children who underwent allogeneic hematopoietic stem cell transplantation. Single-center study

Background. The gastrointestinal form (GI) is a common variant of acute graft-versus-host disease (aGVHD) in children who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). In Russia, there are no large studies devoted to studying the characteristics of the endoscopic picture and tactics of endoscopic diagnosis of patients with GI aGVHD.

Purpose of the study – to develop an optimal algorithm for conducting endoscopic examination in children with cancer who have undergone allo-HSCT, to compare data on the macroscopic picture of detected changes in the gastrointestinal mucosa in accordance with the Cruzz-Correa classification and the Freiburg criteria, to determine the sensitivity, specificity and diagnostic accuracy of endoscopic examination in conducting a differential diagnosis between GI aGVHD and nonspecific/viral lesions of the gastrointestinal tract, as well as assessing the advantages of a comprehensive endoscopic examination in the diagnosis of GI aGVHD.

Materials and methods. In a retrospective study conducted at the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia in the period from January 2021 to September 2023, data from 100 (100 %) patients diagnosed with acute leukemia, under the age of 18 years, who underwent allogeneic HSCT were analyzed. The main study group consisted of patients with suspected GI aGVHD (n = 27; 27 %), who underwent a complex endoscopic examination – esophagogastroduodenoscopy (EGDS) and colonoscopy. When diarrhea syndrome and/or other manifestations of gastrointestinal disorders appeared after allogeneic HSCT in 60 (60 %) patients, to exclude bacterial, viral infections, fungal infections and toxic effects of drug therapy, patients at the first stage underwent microbiological examination of stool and rectal swab. At the second stage, after excluding the above-described factors and suspicion of the development of GI aGVHD, patients (n = 27; 27 %) underwent a comprehensive endoscopic examination, accompanied by the collection of biopsy material from all altered areas of the gastrointestinal mucosa, as well as unchanged areas of the duodenum and rectum. Intestines for histological examination to exclude GVHD and virological studies to exclude acute intestinal infections (Astrovirus, Norovirus genotype 2, Adenovirus F, Rotavirus A), cytomegalovirus infection (CMV), human herpes virus type 6 (HHV-6) and Epstein–Barr Virus (EBV) in the intestinal wall using Polymerase chain reaction (PCR). The results of a comprehensive endoscopic examination were compared with data from laboratory diagnostic methods.

Results. According to the results of complex morphological, immunohistochemical, microbiological, virological studies of biopsy samples of the gastrointestinal mucosa, as well as PCR methods for diagnosing stool and rectal smear, GI aGVHD was confirmed in 22 (81.5 %) of cases (n = 22), of which in 13.6 % of cases (n = 3) there were no visual changes in the mucous membrane. In 5 (18.5 %) patients from the group of patients with suspected GI aGVHD, a diagnosis of viral enterocolitis was established in 14.8 % of cases (n = 4): 1 (3.7 %) patient – adenoviral, 2 (7.4 %) – cytomegalovirus and in 1 (3.7 %) patient – neutropenic enterocolitis; and in 1 (3.7 %) patient – nonspecific changes in the mucous membrane caused by the use of high-dose polychemotherapy. The diagnostic value of forceps biopsy in the diagnosis of GI aGVHD from altered areas of the mucous membrane was 86.4 % (n = 19), from unchanged areas of the duodenum. – 9.1 % (n = 2) and rectum – 4.5 % (n = 1). Significantly more often (p < 0.05) changes in the mucous membrane were detected in the colon (n = 11; 50 %) and duodenum (n = 5; 22.7 %), less often in the stomach (n = 2; 9.1 %) and esophagus (n = 1; 4.5 %) in the form of hyperemia, pastiness (n = 13; 59.1 %) and multiple erosions (n = 5; 22.7 %). Specific changes in the mucous membrane (n = 6; 27.3 %) were determined in the form of multiple erosions merging with each other, occupying most of the surface of the duodenum and colon (n = 5; 22.7 %), and complete detachment of the mucous membrane 12 – duodenum (n = 1; 4.5 %). According to the Cruz-Correa classification, in 9.1 % of cases (n = 2) grade 0 was established, in 9.1 % (n = 2) – I, in 13.6 % (n = 3) – II, in 9.1 % of observations (n = 2) – III and in 4.5 % of observations (n = 1) – IV degree of GI aGVHD of the upper gastrointestinal tract. According to the Freiburg criteria – I degree GI aGVHD of the lower gastrointestinal tract in 4.5 % of cases (n = 1), II – in 36.4 % (n = 8), III – in 13.6 % (n = 3) and IV – in 0 % (n = 0). The sensitivity and diagnostic accuracy of a complex endoscopic examination (EGDS and colon endoscopy) were higher compared with colon endoscopy alone, and amounted to 88.9 % and 55.6 %, 85.2 % and 68.5 %, respectively, and the specificity was in both cases – 81.5 %. The main clinical manifestations of HI aGVHD included symptoms such as diarrhea that is not controlled by medication (n = 17; 77.3 %), anorexia (n = 19; 86.4 %), epigastric pain (n = 22; 100 %), nausea (n = 12; 54.5 %), vomiting (n = 4; 18.2 %), melena (n = 3; 13.6 %).

Conclusion. The diagnosis of GI aGVHD is made on the basis of a comprehensive examination of patients, including clinical picture data, timing of manifestation of gastrointestinal disorders, results of immunohistochemical, microbiological, virological studies of biopsy samples of the gastrointestinal mucosa. Pediatric patients suspected of developing GI aGVHD require a comprehensive endoscopic examination (EGDS and colonoscopy), which is characterized by greater sensitivity compared to colon endoscopy alone, at the second stage of the diagnostic search after excluding viral, fungal and drug etiologies for the development of gastrointestinal disorders. Endoscopic examination must be accompanied by mandatory collection of morphological material from both changed and unchanged areas of the gastrointestinal mucosa.

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