Chronic Graft-Versus-Host Disease (cGVHD) Exacerbation after Sars-Cov-2 Covid Vaccination
Authors: Trunk Andrew D. , Shewan Samuel , Lee Catherine J. , Couriel Daniel R. 
Published: November 2021

Abstract
INTRODUCTION:
Allogeneic hematopoietic cell transplant (allo-HCT) exists as a potential cure to a number of different benign and malignant hematologic conditions. About 50% of patient develop cGVHD, the most important long-term complication of allo-HCT with profound effects on immune recovery. This immunocompromised patient population requires careful consideration regarding approach to vaccination. As the SARS-CoV-2 vaccines were developed and made available at an unprecedented rate, we are learning in real-time how specific vulnerable patient populations are affected, particularly as patients with cGVHD were largely excluded from clinical trials for the SARS-CoV-2 mRNA vaccines. Though the immunomodulatory mechanisms of the Pfizer and Moderna vaccines are poorly understood, societies such as ASH and ASTCT recommend that patients with cGVHD receive it. Here, we report our experience in patients with cGVHD who received the mRNA SARS-CoV-2 vaccine.
METHODS:
We performed this retrospective analysis of all Huntsman Comprehensive Cancer Center patients who underwent allo-HCT between 2013 and 2020. Patients who had a diagnosis of cGVHD requiring systemic therapy and were alive in December 2020, (when the SARS-CoV-2 vaccine became available), were included in the analysis. The clinical data was queried from the bone marrow transplant (BMT) database, and medical records were individually reviewed for documentation of SARS-CoV-2 mRNA vaccination. Patients meeting criteria were screened in clinic for symptoms post-vaccination. We define worsening or flare of disease as an organ upstage of at least 1 by NIH Consensus Criteria scale, in addition to requirement of intervention with a systemic or topical therapy. All patients were consented under a University of Utah IRB-approved protocol for participation in this study.
RESULTS:
A total of 52 patients at our institution met the inclusion criteria of being alive with cGVHD at the time Covid mRNA vaccinations became available. Of these 52 patients, 65.4% (n=34) had had two doses of SARS-CoV-2 vaccine. Of these 34 patients, 26.5% (n=9) experienced worsening of their cGVHD manifestations after vaccination. All 9 of these patients (100%) received the Pfizer vaccine. Mean time between transplant day 0 and flare date was 1,222 days (95% CI 511-1,933). At the time of flare, 3/9 patients were on systemic treatment for cGVHD, 6/9 patients had been tapered off systemic therapy, and half of them were on topical therapies. Three patients (33.3%) experienced GVHD flare after SARS-CoV-2 vaccine dose #1. The remaining 6 (66.7%) experienced flare after dose #2, with a median time to flare of 1.5 days. Five of the 9 patients (55.6%) required systemic steroid therapy, with 2 patients (22.2%) requiring &gt;30 days of treatment. The most common organs involved were skin and eyes. Six patients (66.7%) had resolution of flare symptoms. One patient (11.1%) subsequently developed Covid pneumonia and had relapse of AML.
CONCLUSION:
Though reports have emerged highlighting hematologic and other autoimmune disease recrudescence in response to SARS-CoV-2 vaccination, to our knowledge this is the first large case series demonstrating chronic GVHD flare in response to the vaccine. Almost a third of our cGVHD patients experienced disease flare shortly after vaccination, which raises questions of the degree and mechanism of such heightened immunogenicity in an mRNA vaccine. Consistent with prior studies, most of our patients (66.7%) experienced disease flare after receiving the 2 nd mRNA vaccine dose, Although correlation with vaccine administration does not necessary prove causation of GVHD flare, in counseling patients, the possibility of a severe flare should be weighed against risk of Covid infection.
Figure 1 Figure 1.

Disclosures
Lee: Jazz,: Consultancy; Fresensius Kabi: Consultancy; Kite: Membership on an entity's Board of Directors or advisory committees; Kadmon: Membership on an entity's Board of Directors or advisory committees; CareDx: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding.