Hydroxychloroquine for the treatment of chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) is a major complication of allogen eic bone marrow transplantation. Both the disease and the medications used to treat it are associated with significant morbidity and mortality. The ma nifestations of chronic GVHD often resemble those of autoimmune disorders. Hydroxychloroquine (HCQ) is a 4-aminoquinoline antimalarial drug used for t he treatment of autoimmune diseases. HCQ interferes with antigen processing and presentation, cytokine production, and cytotoxicity and is synergistic with cyclosporine and tacrolimus in vitro. Forty patients with steroid-res istant or steroid-dependent chronic GVHD were enrolled in a phase 2 trial o f HCQ 800 mg (12 mg/kg) per day. Three complete responses and 14 partial re sponses were seen in 32 evaluable patients (53% response rate). All respond ers tolerated a >50% reduction in their steroid dose while receiving HCQ. C linical response occurred at a median of 8 weeks (range, 4 to 24 weeks). No hematologic, hepatic, renal, or retinal toxicity was associated with HCQ. In light of its mechanisms of action, clinical activity for GVHD, and low t oxicity profile, HCQ may be useful in a multiagent approach for the treatme nt of extensive chronic GVHD.