Abstract
Graft-versus-host disease (GVHD) is a major complication following hematopoietic cell transplantation. While prophylaxis of GVHD has improved, treatment for GVHD remains unsatisfactory. PG490–88, a semi-synthetic derivative of a novel compound purified from a Chinese herb, is very effective in prevention of both acute and chronic GVHD. In this study, we tested whether PG490–88 is effective in treating established GVHD. The study was performed in a clinically relevant MHC-matched and minor mismatched model (B10.D2 to BALB/c). BALB/c (H2d, Mls-2a, Mls-3a) mice were lethally irradiated (8.5 Gy) and transplanted with 1x107 bone marrow cells and 1x108 spleen cells obtained from B10D.2 (H2d, Mls-2b, Mls-3b) mice. PG490–88 was administered intraperitoneally (i.p.) daily at a dose of 0.0535 mg/kg/day starting on day +15 post transplantation when the clinical signs of GVHD were first observed. Therefore, all animals in both vehicle control and PG490–88-treated groups developed GVHD before the treatment was started. After treatment, there was no difference in the severity of clinical GVHD between the treated and the control groups. However, PG490–88-treated mice survived significantly longer than the mice in the vehicle control group (Figure, median survival time: 50 vs. 65 days, P<0.0001). These data suggest that PG490–88 as a single agent is active in the therapy of established GVHD. Further preclinical studies will determine optimal schedules and combinations that could be utilized in clinical studies.
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