Recognizing the Toll of Oral Damage From Graft-Versus-Host Disease After Stem Cell Transplant

Posted in News Release  |  Tagged cancer, Graft-Versus-Host Disease

WASHINGTON (August 20, 2019) — Too little has been done to understand and effectively treat chronic graft-versus-host disease (cGVHD) that occurs very commonly in the mouth following a stem cell transplant, says a team of investigators.

Their review of cGVHD, in which donor cells can push the patient’s immune system (host) to attack what it recognizes as “foreign” cells (graft) in the oral cavity, presents the state of the science through an in-depth review of the scientific and clinical importance of this disease, the critical importance of accurate assessment, current pathobiological model, evidence gaps in our understanding of this disease and treatment effects, and strategies to advance the science.

The review by researchers from Georgetown University Medical Center, the National Cancer Institute, the National Institute of Dental and Craniofacial Research, and the Fred Hutchinson Cancer Research Center is published in the August 2019 Journal of the National Cancer Institute (JNCI) Monograph.

Stem cell transplantation has been a major advance in treatment of numerous blood and immune system cancers. Thousands of patients’ lives have been saved with the use of donor stem cells through “allogeneic” transplants. This kind of transplant gives the patient closely immunologically matched donor stem cells to replace those cells lost from the high doses of chemotherapy and the radiation therapy used before the stem cell transplant.

But long-term negative health consequences may occur from stem cell transplant, including the serious complication cGVHD. The risk of developing this disease is often dependent on how well “matched” donor stem cells are to the recipient. Chronic GVHD can occur in many body sites, such as the lungs, GI tract, skin and, very commonly, the oral cavity.

“Currently there is no optimum treatment for oral cGVHD. The majority of treatments have not been evidence-based, and conducting clinical research is challenging,” says the paper’s senior author, Jane M. Fall-Dickson, PhD, RN, in the Department of Professional Nursing Practice at Georgetown’s School of Nursing & Health Studies and a member of Georgetown Lombardi Comprehensive Cancer Center.

Clinical trials are needed to test novel targeted agents, but before these drugs can be developed and tested in randomized clinical trials, investigators need to decode the immunobiology of cGVHD, the authors say.

Oral cGVHD affects from 45% to 83% of patients post allogeneic stem cell transplant, the researchers say. The difficulty in calculating the actual percentage illustrates the lack of information available on this frequent and serious oral side effect, says Fall-Dickson.

Symptoms related to oral cGVHD may often be severe. For example, pain related to oral ulcerations and sensitivity to food and drink is frequently reported. Additionally, dry mouth is common, which can reduce ability to speak, swallow and chew.

“These significant symptoms may lead to dramatically decreased caloric intake, leading to weight loss and malnutrition, and increased use of health care services,” Fall-Dickson explains. “These issues often affect health-related quality of life, and in some cases, survival, as when oral ulcers become infected.”

The most commonly used therapies for oral cGVHD are topical high-dose, potent corticosteroids and calcineurin inhibitors.

But there has been some progress, Fall-Dickson says. “The last decade of focused clinical research effort by the National Institutes of Health cGVHD Consensus Development Project and other U.S. and international groups has resulted in more defined treatment outcomes, a valid and reliable oral cGVHD assessment tool, and increasing elucidation of a model for studying this oral disease in the lab.”

And the future may be brighter still. “There has been a recent increase in interest in conducting preclinical and clinical studies in oral cGVHD as seen through the testing of novel topical therapeutics and therapeutics approved for other conditions,” she says. “The success of stem cell transplantation is well recognized, and now I think the need to focus on this serious side effect is being recognized.”

Co-authors of this state-of-the-science paper are Steven Z. Pavletic, MD, MS, from NIH’s National Cancer Institute, and Jacqueline W. Mays, DDS, MHSc, PhD, from NIH’s National Institute of Dental and Craniofacial Research; and Mark M. Schubert, DDS, MSD, from Fred Hutchinson Cancer Research Center.

The paper was originally presented at a conference that was funded in part by a grant (R13 DE19330) from the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH). 

The authors report having no personal financial interests related to this paper.