{"entity":{"id":"gvhd-chronic-overview","kind":"technology","name":"Chronic graft-versus-host disease","aka":["chronic GvHD","chronic GVHD","cGVHD","cGvHD","chronic graft versus host disease"],"tldr":"After a donor transplant the new immune system can treat the body it has landed in as foreign. When that goes on past the first few months it is called chronic graft-versus-host disease, and it affects roughly four in ten adults. It is treatable and often improves, and the same donor immunity also keeps the leukaemia away, so the aim is to control it rather than abolish it.","summary":"Chronic graft-versus-host disease is an alloimmune and autoimmune syndrome in which donor-derived lymphocytes, and the fibrosis and tissue damage that follow them, injure the recipient's skin, mouth, eyes, gut, liver, lungs, joints and genital tract. It is the leading cause of late non-relapse illness and death after allogeneic transplant, and unlike most complications of cancer treatment it can last for years and need treatment for years.\n\nHow common it is depends on who is counted and when. A European multicentre analysis of 317 patients transplanted in 2017 found a cumulative incidence of chronic GvHD of 43.0 per cent in all adult recipients and 50.2 per cent in the adult at-risk cohort by the end of the study, with late acute GvHD in a further 10.5 per cent of adults and 4.8 per cent of children. Onset was de novo in 42.0 per cent, quiescent after resolved acute disease in 52.1 per cent and progressive from unresolved acute disease in 5.9 per cent. The CIBMTR looked at the direction of travel across 26,563 patients transplanted for acute leukaemia, chronic myeloid leukaemia or myelodysplastic syndrome over twelve years and found the incidence rising, not falling: odds ratio 1.19 for more recent years, a trend that persisted after adjusting for donor type, graft type and conditioning intensity, while non-relapse mortality among those who developed it fell.\n\nThe reason it is not simply a complication to be eliminated is the graft-versus-leukaemia effect that travels with it. In the 2017 European cohort, overall survival in the adult at-risk group was higher in patients who developed chronic GvHD than in those who did not, 78.9 per cent against 66.2 per cent, because relapse was less common, 14.5 per cent against 27.2 per cent. The survival advantage was present for mild and moderate disease and not for severe disease. That single finding explains the shape of the whole field: prophylaxis and treatment aim at the severe end, and a person with limited skin or mouth disease is not in a worse position overall than a person with none.\n\nThe syndrome is also wider than the eight organs the consensus criteria score. A single-centre review of 623 transplants applied the NIH task force's provisional criteria for atypical manifestations and found them in 102 patients, 16.4 per cent of the whole cohort and a quarter of all chronic GvHD cases, with 14 patients having only atypical disease. The commonest were immune-mediated cytopenias in 24.5 per cent, renal involvement in 13.7 per cent and serositis in 13.7 per cent. Prior acute GvHD and donor lymphocyte infusion were risk factors for both classic and atypical disease; total body irradiation was an independent risk factor for atypical manifestations only. Non-relapse mortality was significantly increased by atypical disease, driven by a few manifestations such as renal involvement, restrictive lung disease and peripheral neuropathy, and not by others such as thyroid or pancreatic involvement.\n\nWhat a reader should take from this: chronic GvHD is common, it is scored in a defined way, most of it is mild or moderate, it is usually treatable, and the people who do worst are those with severe disease, lung involvement or disease that does not respond to steroids. Each of those has its own record below.","status":"established","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Graft-versus-host_disease","links":[{"label":"Jagasia et al., NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.12.001"},{"label":"Langer et al., Retrospective analysis of the incidence and outcome of late acute and chronic graft-versus-host disease: an analysis from transplant centers across Europe (Front Transplant 2024)","url":"https://doi.org/10.3389/frtra.2024.1332181"},{"label":"Arai et al., Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the CIBMTR (Biol Blood Marrow Transplant 2015)","url":"https://doi.org/10.1016/j.bbmt.2014.10.021"},{"label":"Doering et al., Incidence and outcome of atypical manifestations of chronic graft-versus-host disease (Transplant Cell Ther 2023)","url":"https://doi.org/10.1016/j.jtct.2023.09.016"},{"label":"Inamoto and Lee, Late effects of blood and marrow transplantation (Haematologica 2017)","url":"https://doi.org/10.3324/haematol.2016.150250"}],"tags":["rejuvenation","survivorship","transplant","gvhd","immune"],"related":["gvhd-nih-consensus-criteria","gvhd-organ-by-organ","gvhd-lung-bronchiolitis-obliterans","gvhd-prophylaxis","gvhd-ruxolitinib-steroid-refractory","gvhd-belumosudil-axatilimab-ibrutinib","gvhd-photopheresis","rejuv-tx-late-effects-overview","rejuv-tx-what-to-ask-for"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct"],"targets":[],"drugs":["ruxolitinib","belumosudil","ibrutinib"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","late-effects","conditioning-regimen","secondary-malignancy"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Donor T cells that survive conditioning and thymic selection in a recipient whose thymus has been damaged by conditioning and by acute GvHD encounter host antigens without the usual central tolerance. The resulting alloreactive and autoreactive T and B cell responses drive a three-phase process: early tissue injury and inflammation, chronic dysregulated T and B cell activation with germinal-centre and follicular helper T cell involvement, and finally aberrant tissue repair with macrophage-driven and TGF-beta-driven fibrosis. The three phases are why drugs as different as a JAK inhibitor, a ROCK2 inhibitor, a BTK inhibitor and a CSF1R antibody all have activity: each hits a different phase.","strengths":["Defined by published consensus criteria, so severity can be scored and compared","Most disease is mild or moderate and most patients improve on treatment","The donor immunity that causes it also suppresses relapse, and in a European cohort mild and moderate disease carried better overall survival than no chronic GvHD at all","Several licensed drugs now exist for disease that does not respond to steroids, where before 2017 there were none"],"limitations":["Incidence has risen over time rather than fallen","Severe disease, and lung involvement in particular, remains hard to treat","Treatment runs for years and the immunosuppression it requires carries its own infection risk","A quarter of cases include manifestations outside the eight scored organs, which are easy to miss"]},"route":"/technologies/gvhd-chronic-overview/","neighbours":{"technology":[{"id":"rejuv-tx-what-to-ask-for","kind":"technology","name":"After a transplant or cell therapy: what to ask for","route":"/technologies/rejuv-tx-what-to-ask-for/"},{"id":"gvhd-belumosudil-axatilimab-ibrutinib","kind":"technology","name":"After ruxolitinib: belumosudil, axatilimab and ibrutinib in chronic GvHD","route":"/technologies/gvhd-belumosudil-axatilimab-ibrutinib/"},{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"gvhd-organ-by-organ","kind":"technology","name":"Chronic GvHD organ by organ: skin, mouth, eyes, gut, liver, joints and genital tract","route":"/technologies/gvhd-organ-by-organ/"},{"id":"gvhd-photopheresis","kind":"technology","name":"Extracorporeal photopheresis for graft-versus-host disease","route":"/technologies/gvhd-photopheresis/"},{"id":"gvhd-nih-consensus-criteria","kind":"technology","name":"How chronic GvHD is diagnosed and scored: the NIH consensus criteria","route":"/technologies/gvhd-nih-consensus-criteria/"},{"id":"rejuv-tx-infection-by-phase","kind":"technology","name":"Infection risk after transplant and cell therapy, phase by phase, and the prophylaxis that follows it","route":"/technologies/rejuv-tx-infection-by-phase/"},{"id":"rejuv-tx-late-effects-overview","kind":"technology","name":"Late effects after a stem cell transplant","route":"/technologies/rejuv-tx-late-effects-overview/"},{"id":"gvhd-prophylaxis","kind":"technology","name":"Preventing graft-versus-host disease, and what prevention costs","route":"/technologies/gvhd-prophylaxis/"},{"id":"rejuv-tx-quality-of-life","kind":"technology","name":"Quality of life after transplant and cell therapy","route":"/technologies/rejuv-tx-quality-of-life/"},{"id":"rejuv-tx-second-cancers","kind":"technology","name":"Second cancers after allogeneic transplant","route":"/technologies/rejuv-tx-second-cancers/"},{"id":"rejuv-tx-survival-after-transplant","kind":"technology","name":"Survival after transplant, and why the curve never quite rejoins the population","route":"/technologies/rejuv-tx-survival-after-transplant/"},{"id":"gvhd-lung-bronchiolitis-obliterans","kind":"technology","name":"The lungs after transplant: bronchiolitis obliterans syndrome","route":"/technologies/gvhd-lung-bronchiolitis-obliterans/"},{"id":"gvhd-ruxolitinib-steroid-refractory","kind":"technology","name":"When steroids fail: ruxolitinib for steroid-refractory GvHD","route":"/technologies/gvhd-ruxolitinib-steroid-refractory/"}],"section":[{"id":"rejuvenation","kind":"section","name":"Recovery & Rejuvenation","route":"/fronts/rejuvenation/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"drug":[{"id":"belumosudil","kind":"drug","name":"Belumosudil","route":"/drugs/belumosudil/"},{"id":"ibrutinib","kind":"drug","name":"Ibrutinib","route":"/drugs/ibrutinib/"},{"id":"ruxolitinib","kind":"drug","name":"Ruxolitinib","route":"/drugs/ruxolitinib/"}],"term":[{"id":"conditioning-regimen","kind":"term","name":"Conditioning regimen (myeloablative, reduced-intensity)","route":"/terms/conditioning-regimen/"},{"id":"gvhd","kind":"term","name":"Graft-versus-host disease (GVHD) and graft-versus-leukaemia","route":"/terms/gvhd/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"},{"id":"secondary-malignancy","kind":"term","name":"Secondary malignancy (therapy-related cancer)","route":"/terms/secondary-malignancy/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}]}}