Going beneath the skin: A closer look at serositis in cGVHD

Chronic graft-versus-host disease (cGVHD) is a complex immune complication of allogeneic hematopoietic stem cell transplantation (HCT), in which donor immune cells turn against the recipient’s healthy tissues. While it’s often visible in the skin, eyes, and mouth, cGVHD can also strike deeper—sometimes inflaming the thin membranes around vital organs, a condition known as serositis. This inflammation can cause discomfort from swelling, fluid buildup, and breathing difficulties, yet it remains an under-recognized challenge in cGVHD care.

While 10-30% of patients receiving HCT develop cGVHD, only a small subset are further afflicted by serositis, making this condition difficult for clinicians to study due to a lack of data. A new study published in Transplantation and Cellular Therapy from Dr. Stephanie Lee’s group is attempting to overcome this barrier by leveraging the largest reported cohort to date of serositis cases linked to cGVHD, providing a detailed view of who gets this complication, how it unfolds, and what happens next.

Among 4,322 adults who underwent HCT at Fred Hutch between 1998 and 2021, 50 patients (1%) developed cGVHD-associated serositis. Fluid build-up around the lungs was the most common (76%), followed by the pericardium, which surrounds the heart (62%), and ascites within the abdomen (12%), with nearly half of patients experiencing more than one type of fluid build-up. The median onset was 1.3 years post-transplant, though ascites occurred later (median 3.8 years). Most patients (96%) had received peripheral blood grafts and over 60% had pre-existing cGVHD prior to serositis onset.

“Serositis is a rare late complication of transplantation but causes a lot of symptoms for the people affected by it,” says Dr. Lee. “Because of its rarity, we don’t know much about this complication and treatment varies a lot. Using our long-term follow-up database, we were able to look back and identify a group of affected patients and look at their courses. Most people responded to increased immunosuppression but about 30% died within three years of developing serositis.”

While immunosuppression was often employed—with prednisone used in three-quarters of cases—there were some other therapeutic avenues. Surgical methods were used to physically drain the fluids in 32% of patients. Complete or partial responses were achieved in most cases, but the study reported recurrence in 26% of patients. Survival after diagnosis was favorable for many, with 86% of patients surviving past one year and 66% surviving past three years. Compared with prior reports, the timing of onset and affected organ patterns were similar, and treatment remained centered on corticosteroids and conventional immunosuppressants rather than newer FDA-approved agents.

“It will be hard to do prospective studies because of the rarity of this complication,” Dr. Lee notes, “but I am hoping to use our network of collaborating transplant centers to gather enough cases to study why people get serositis.” That next step—identifying the risk factors and biological drivers—could help clinicians not only recognize serositis earlier but also tailor prevention and treatment strategies for those most at risk. While this study offers the most comprehensive look yet at cGVHD-associated serositis, it also highlights just how much remains unknown about this rare but impactful complication.

Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Member Dr. Stephanie Lee contributed to this research.

The spotlighted research was funded by the National Institutes of Health.

Te C, Elahi T, Samples K, Onstad L, Lee SJ. 2025. Serositis Associated with Chronic Graft-Versus-Host Disease. Transplantation and Cellular Therapy. DOI: 10.1016/j.jtct.2025.07.002.