Chronic Graft Versus Host Disease

Reviewed and revised 29 August 2014

OVERVIEW

• Chronic Graft vs Host Disease is organ dysfunction occurring > 100 days post transplantation
• distinct clinical syndrome from acute GVHD
• pathophysiology poorly understood
• there can be an overlap period, where patients have both acute and chronic GVHD
• affects 50% of HSCT recipients

CLINICAL FEATURES

• chronic GVHD resembles spontaneously occurring autoimmune disorders, e.g. scleroderma
• Organs typically  affected: skin (lichenoid and sclerotic rashes), mouth, joints, liver, eyes, gastrointestinal tract, and occasionally lungs

RISK FACTORS

• older patient
• CMV seropositive
• male who receives a stem cell transplant from a multiparous woman

INVESTIGATIONS

• tissue biopsies of skin, liver and stomach: apoptosis, infiltration of lymphocytes
• investigations to exclude other conditions in the differential diagnosis

MANAGEMENT

• Therapy relies on many of the same medications used to treat acute GVHD
• patients require prolonged immunosuppressive treatment for an average of 2 to 3 years from the initial diagnosis
• Glucocorticoids +/- calcineurin inhibitors (i.e., cyclosporine or tacrolimus) remain the standard initial treatment of chronic GVHD, but the outcomes are often not satisfactory, particularly for patients with high-risk features
• Secondary options unproven: extracorporeal photopheresis, rituximab, sirolimus, mycofenolate mofetil, imatinib, pentostatin and infusion of mesenchymal stem cells

PROGNOSIS

• can worsen survival due to more transplant-related mortality
• infection from immunosuppression and disease-associated immune dysfunction accounts for most deaths
• prolonged treatment is often required (e.g. months-to-years)
• can also have a graft versus tumour effect

References and Links

LITFL

• CCC — Acute GVHD

Journal articles

• Carpenter PA. How I conduct a comprehensive chronic graft-versus-host disease assessment. Blood. 2011 Sep 8;118(10):2679-87. PubMed PMID: 21719600.
• Inamoto Y, Flowers ME. Treatment of chronic graft-versus-host disease in 2011. Curr Opin Hematol. 2011 Nov;18(6):414-20. PMC3276600.