Association of Day-100 Oral GVHD with subsequent Chronic GVHD Diagnosed by NIH 2005 Consensus Criteria and Treated with Systemic Immunosuppression

Abstract

University of Washington Abstract Association of Day-100 Oral GVHD with subsequent Chronic GVHD Diagnosed by NIH 2005 Consensus Criteria and Treated with Systemic Immunosuppression Niveditha Venkatesh Chair of Supervisory Committee: Mark M. Schubert DDS, MSD Department of Oral Medicine Background: Graft-versus-host disease (GVHD) is a significant cause of morbidity and mortality post hematopoietic transplantation (HCT). The oral cavity is a common site of chronic GVHD and can be one of the first sites of involvement. Clinical and laboratory investigations have been utilized within the allogeneic transplant population to identify or predict chronic GVHD development near the time of departure from the transplant service (approximately Day +70-120 post-HCT). Such investigations routinely include oral examinations to assess for GVHD-related findings; however, there are currently no published studies in the literature that have exclusively examined the specific association between oral GVHD, based solely on clinical findings at departure and the development of future systemic chronic GVHD. Aim: To examine the association between oral mucosal GVHD at the time of departure evaluation (day+ 70-120) in patients without prior evidence of other chronic GVHD activity and the development of subsequent chronic GVHD requiring treatment with systemic immunosuppression. Methods: The electronic medical records (EMRs) of 642 consecutive adult patients (≥ 21 years of age) who received their first allogeneic HCT at Seattle Cancer Care Alliance (SCCA; Seattle, WA, USA) between January 1st 2010- June 30th 2014 were reviewed for inclusion in the study. Oral mucosal GVHD disease status was determined based on review of oral medicine “departure” examination records (departure exams were completed between day +70-120 post-HCT). Demographic data, transplant protocols, and event timeline information were obtained from the Fred Hutchison Cancer Center (FHCRC) optical web library and the Gateway database. In cases where an official oral GVHD diagnosis was not made or when oral examination findings were non-specific, clinical descriptors were independently reviewed by three oral medicine providers and, a discussion was held until a consensus on oral mucosal GVHD status was reached. The diagnosis of oral mucosal GVHD was based on the NIH diagnostic criteria. The FHCRC optical web library gateway database was reviewed to determine the primary outcome variable “future chronic GVHD treated with systemic immunosuppression”. All cases of chronic GVHD were diagnosed based on the 2005 NIH consensus criteria. Univariate and multivariable logistic regression were used to examine the association between a diagnosis of oral mucosal GVHD at and the development of chronic GVHD. All analyses were performed using SAS (Statistical Analysis Software) v9.4. Results: Five hundred and thirty-eight patients met the criteria for inclusion in the study. In both the univariate and multivariable analyses, clinical oral mucosal GVHD at departure without other chronic GVHD activity prior or at departure was associated with an increased risk for subsequent development of chronic GVHD requiring treatment with systemic immunosuppression. In the univariate analysis, those with oral mucosal GVHD at departure were 1.5 times as likely to develop chronic GVHD compared to those without chronic systemic GVHD at departure (odds ratio (OR)=1.5, 95% CI 1.1-2.2, p=0.02). After adjusting for risk factors related to the development of chronic GVHD (specifically recipient age, patient/donor gender, donor relationship, graft source, acute GVHD grades 2-4, conditioning regimen and prednisone treatment at time of departure), the association was similar (OR=1.6, 95% CI 1.2-2.4, p=0.01). Conclusion: A clinical diagnosis of oral mucosal GVHD at the time of departure was found to be associated with increased risk for subsequent development of systemic chronic GVHD. This study highlights the potential value of examining patients 70-120 days’ post HCT to determine the presence of oral GVHD-related changes. With future studies supporting such an association, it would reaffirm the value of diagnosing oral GVHD accurately and in a timely manner to improve not only oral health and patient comfort but perhaps even overall survival. Patients with an oral GVHD diagnosis at departure should be advised of the increased risk of chronic GVHD development and receive appropriate education to allow for early recognition and reporting of chronic GVHD signs and symptoms to their medical team.