FK506 TREATMENT OF GRAFT-VERSUS-HOST DISEASE DEVELOPING OR EXACERBATING DURING PROPHYLAXIS AND THERAPY WITH CYCLOSPORINE AND OR OTHER IMMUNOSUPPRESSANTS/

A phase II study of the efficacy and safety of FK506, a new potent imm unosuppressant, has been conducted in 49 patients with GVHD after allo geneic BMT. Eighteen patients with acute GVHD and 31 with chronic GVHD entered the study, FK506 was administered at an initial dose of 0.05 mg/kg i.v. or 0.15 mg/kg orally twice a day to those whose GVHD had be come uncontrollable with cyclosporin and/or other immunosuppressants, The response to FK506 was evaluated in 13 patients with acute and 26 w ith chronic GVHD, A marked response was observed in 5 and a good respo nse in 2 of 13 patients with acute GVHD, For those with chronic GVHD, the response was marked in 2 patients, good in 10 and poor in 8, The m ost common adverse effects were renal toxicity (53.1%), followed by na usea and vomiting (30.6%) and a feeling of warmth (18.4%), There was a correlation between renal toxicity and whole blood levels of FK506. T he dose should be adjusted to keep a trough level between 15 and 25 ng /ml, FK506 is promising in the treatment of both acute and chronic GVH D, even if it is intractable with other immunosuppressants, and may be most effective if administered early in the course of GVHD.