Graft-Versus-Host Disease in Hematopoietic Stem Cell Transplantation

Graft-versus-host disease (GVHD) remains the principal complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT), arising when donor immune cells mount an attack on recipient tissues. Acute GVHD (aGVHD) typically presents within the first 100 days post-transplant, most commonly affecting skin, liver and gastrointestinal tract, whereas chronic GVHD (cGVHD) emerges later and can involve multiple organs in a pattern reminiscent of autoimmune disorders. The pathophysiology of GVHD is initiated by tissue damage from conditioning regimens, which promotes activation of donor T cells that recognise host antigens and release pro-inflammatory cytokines. This cascade leads to further antigen presentation, target-organ injury and impaired thymic recovery. In parallel, the graft-versus-leukaemia (GvL) effect leverages the capacity of donor T cells to eradicate residual malignant cells, underscoring the delicate balance between therapeutic benefit and toxicity. Standard prophylaxis combines calcineurin inhibitors with methotrexate or mycophenolate mofetil, while first-line treatment of established GVHD centres on high-dose corticosteroids. However, approximately half of patients with aGVHD become steroid-refractory, prompting exploration of targeted agents, cellular therapies and predictive biomarkers. Advances in the understanding of immune reconstitution, T-cell subsets and tissue-specific homing have paved the way for novel interventions designed to mitigate GVHD without abrogating GvL, thereby improving long-term survival and quality of life across diverse patient populations.

Research from Nature Portfolio

Recent phase III data demonstrate that adding a gut-selective anti-α4β7 integrin monoclonal antibody to standard calcineurin inhibitor-based prophylaxis significantly reduces the incidence of lower-gastrointestinal aGVHD. In a randomised, double-blind trial, recipients of unrelated donor allo-HSCT who received the integrin inhibitor exhibited markedly higher rates of lower-GI aGVHD-free survival at six months compared with placebo, without an increase in non-relapse mortality or serious adverse events. This approach offers a targeted strategy to inhibit lymphocyte trafficking to the gut, attenuating local inflammation while preserving systemic immunity.

Graft-Versus-Host Disease in Hematopoietic Stem Cell Transplantation publication trend

The graph below shows the total number of articles in graft-versus-host disease in hematopoietic stem cell transplantation across all publications each year (not limited to Nature Index journals).

Technical terms

Allogeneic haematopoietic stem cell transplantation (allo-HSCT): Transfer of donor-derived blood-forming stem cells into a recipient following myeloablative or reduced-intensity conditioning.

Acute graft-versus-host disease (aGVHD): Early immune-mediated tissue injury by donor T cells, generally occurring within 100 days post-transplant.

Chronic graft-versus-host disease (cGVHD): Late-onset immune-driven fibrotic and inflammatory processes involving one or more organs, resembling autoimmune phenomena.

Graft-versus-leukaemia effect (GvL): Beneficial donor T-cell activity directed against residual malignant cells, contributing to disease control.

Steroid-refractory: Failure to achieve adequate clinical response following standard systemic corticosteroid therapy.

Janus kinase (JAK) inhibitor: Small-molecule agent that blocks JAK1/JAK2 signalling to modulate cytokine-driven immune activation.

Anti-α4β7 integrin monoclonal antibody: Biologic therapeutic that prevents migration of gut-homing lymphocytes, reducing intestinal inflammation.

References

1. Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial. Nature Medicine (2024).
2. Pathophysiology of GvHD and Other HSCT-Related Major Complications. Frontiers in Immunology (2017).
3. Treatment and unmet needs in steroid-refractory acute graft-versus-host disease. Leukemia (2020).
4. Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study. Bone Marrow Transplantation (2019).