Graft-versus-Host Disease — Transplant Complication

Graft-versus-host disease arises following an allogeneic haematopoietic stem cell transplantation, wherein the donor's immune system reconstitutes inside the recipient's body. The fundamental driver of this condition is the activation of mature donor T-lymphocytes, which perceive host human leukocyte antigens (HLAs) and minor histocompatibility antigens as non-self, initiating widespread immune-mediated tissue destruction.

GVHD is conventionally categorised into acute and chronic forms based on clinical presentation, timing, and immunopathology. Acute GVHD typically manifests within the initial months following transplantation, predominantly targeting the epithelial surfaces of the skin, gastrointestinal tract, and hepatic system. Chronic GVHD can arise later, presenting as a multisystem, auto-immune-like disorder characterised by fibrosis, tissue sclerosis, and dysfunction across numerous organs, including the oral mucosa, eyes, lungs, and neuromuscular structures.

For transplant recipients, GVHD is a double-edged sword that requires careful clinical management. Mild forms of GVHD can be beneficial because donor immune cells also attack residual leukaemia or lymphoma cells, lowering relapse risk. However, severe or unmanaged GVHD can lead to organ failure, secondary infections, and long-term morbidity. Being vigilant about emerging symptoms—such as unexplained skin redness, intestinal cramping, jaundice, or dry mucous membranes—allows clinical teams to introduce immunosuppressive therapies promptly, mitigating tissue damage while preserving the curative benefits of the allogeneic stem cell graft.

Diagnosis is primarily clinical, supported by targeted diagnostic tests. Doctors assess donor-recipient HLA compatibility prior to transplant via high-resolution genetic typing. Following transplantation, tissue biopsies—such as punch biopsies of the skin, endoscopic biopsies of the stomach or colon, or liver biopsies—confirm GVHD histologically. Blood tests, including liver function panels (measuring bilirubin and alkaline phosphatase) and complete blood counts, track systemic involvement, organ inflammation, and overall recovery.

GVHD occurs almost exclusively in people undergoing allogeneic stem cell or bone marrow transplantation. This intensive treatment is predominantly utilised for haematological malignancies, including acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), myelodysplastic syndromes (MDS), and severe forms of myelofibrosis. It is also encountered in individuals receiving donor transplants for refractory non-Hodgkin lymphoma, Hodgkin lymphoma, and certain severe non-malignant marrow failure syndromes.

Preventing and treating GVHD involves targeted immunosuppression. Prophylactic regimens often combine calcineurin inhibitors (such as tacrolimus or ciclosporin) with methotrexate or mycophenolate mofetil. When acute or chronic GVHD develops, high-dose corticosteroids represent the standard first-line treatment. For steroid-refractory cases, targeted therapies including Janus kinase (JAK) inhibitors (like ruxolitinib), BTK inhibitors (such as ibrutinib), or extracorporeal photopheresis are utilised to dampen donor T-cell activity while managing infection risks.