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Updated: Jun 13, 2026

Bone Marrow Transplantation Platform to Investigate the Role of Dendritic Cells in Graft-versus-Host Disease
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Chronic graft-versus-host disease.

Yishan Ye1,2, Bipin Savani3, Florent Malard2

  • 1Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Nature Reviews. Disease Primers
|June 11, 2026
PubMed
Summary

Chronic graft-versus-host disease (cGVHD) is a serious complication after transplants. New treatments show promise, but challenges like drug resistance and varied patient responses persist, requiring better supportive care and research.

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Published on: August 29, 2012

Area of Science:

  • Immunology
  • Oncology
  • Transplantation Medicine

Background:

  • Chronic graft-versus-host disease (cGVHD) is a significant complication following allogeneic haematopoietic cell transplantation (allo-HCT), affecting 30-70% of recipients.
  • It leads to substantial morbidity, impairs quality of life, and is a leading cause of non-relapse mortality in allo-HCT survivors.
  • The condition involves complex immune dysregulation, including T and B cell activation, regulatory T cell dysfunction, and fibrosis mediated by macrophages and fibroblasts.

Purpose of the Study:

  • To review the current landscape of cGVHD treatment, highlighting challenges and future directions.
  • To discuss approved and emerging therapies targeting specific pathways involved in cGVHD pathogenesis.
  • To emphasize the need for improved biomarkers, antifibrotic strategies, and multidisciplinary care.

Main Methods:

  • Literature review of cGVHD pathogenesis, current treatments, and emerging therapies.
  • Analysis of approved second-line treatments (ibrutinib, ruxolitinib, belumosudil, axatilimab) and their targeted pathways.
  • Discussion of persistent challenges including disease heterogeneity, drug resistance, and supportive care.

Main Results:

  • Glucocorticoids are first-line, but ~50% of patients are steroid-refractory or dependent, requiring alternative immunosuppression.
  • Four FDA-approved second-line treatments target distinct pathways: B cell signaling, JAK-STAT, ROCK2, and CSF1R.
  • Emerging therapies like rovadicitinib show potential, yet significant challenges in treatment resistance and managing manifestations like lung and skin sclerosis remain.

Conclusions:

  • Despite advances, cGVHD treatment faces challenges due to its heterogeneous nature, drug resistance, and the need for better supportive care.
  • Further research into mechanistic insights, antifibrotic therapies, and organ-specific interventions is crucial.
  • Biomarker development for early diagnosis and personalized medicine, alongside multidisciplinary care, is essential for improving patient outcomes.