Early Positive Biopsy in Asymptomatic Post-Allogenic Hematopoietic Stem Cell Transplant Recipients Is Not Associated with the Development of Clinical Chronic Graft-Versus-Host Disease

Abstract

Background Histopathology is the gold standard for diagnosis of chronic graft-versus-host disease (cGVHD). The phenomenon of a positive early oral biopsy in the absence of clinical symptoms (asymptomatic positive biopsy [APB]) has been previously noted in the literature. but the diagnostic and prognostic value of this finding has not been investigated. The purpose of this study was to investigate the diagnostic and prognostic value of this phenomenon. Methods Oral buccal mucosal biopsies were taken near day 90 post-transplant from patients who had undergone allogeneic hematopoietic stem cell transplantation (alloHSCT) at the NIH Clinical Center (NCT00391170), and who were free of clinical oral GVHD. Scanned, de-identified images of hematoxylin and eosin (H&E)-stained slides of baseline oral biopsies were evaluated by four oral pathologists experienced in evaluating oral GVHD. The incidence of APB and the individual histopathologic features most common in the APB samples were calculated. Pathology data were combined with clinical and demographic data, including pre-transplant conditioning, incidence of acute GVHD, and incidence of mucositis, to determine clinical significance and predictive value of the histopathologic findings. Results At baseline, based on agreement of three of four pathologists' reads, 17 of the 38 biopsies (45%) analyzed were classified as possible or likely oral GVHD. All cases (100%) exhibited inflammation in the lamina propria, and most of this was lymphocytic (94%), while acanthosis was frequently noted (82%). This pathological assessment was not predicted by type of transplant (myeloablative or not), prior acute GVHD or prior mucositis. Patients with cGVHD at more than one site within one year post alloHSCT were likely to also have clinical oral GVHD (Fishers exact test, p Conclusions Oral mucosal biopsies taken early after transplant (