Safety and Potential Efficacy of Low Dose Methotrexate for Treatment of Chronic Graft-Versus-Host Disease.

Low dose methotrexate (MTX) is widely used for treatment of autoimmune diseases because of its anti-inflammatory activity. Encouraged by this practice, we have administered low dose MTX for treatment of refractory chronic GVHD, with the goal of reducing the amount of prednisone needed to control the disease. Fourteen patients with refractory chronic GVHD were treated with MTX at a dose of 7.5 mg/m² per week for 3–50 weeks. All patients had involvement of the oral cavity and 11 of the 14 (78%) had skin involvement, often with scleroderma or fasciitis. The median duration of chronic GVHD at the start of MTX therapy was 38 (range 1–135) months. In this retrospective review, we found no grade 3–4 toxicities, and none of the patients required blood transfusion or treatment with hematopoietic growth factors. In 10 patients (71%), chronic GVHD could be adequately controlled with prednisone at doses below 1 mg/kg every other day without the addition of other immunosuppressive agents. Four patients decreased the amount of concomitant immunosuppressive treatment, 5 continued with the same regimen, 4 required an increase in immunosuppressive treatment, and one decided to discontinue all treatment. Improvement or resolution was observed most frequently in the gastrointestinal tract (80%) and skin (50%). From this preliminary analysis, MTX appears to be a well tolerated, inexpensive and possibly steroid-sparing immunosuppressive agent that is worthy of further evaluation in prospective trials for treatment of chronic GVHD.