Response to thalidomide therapy in refractory chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) refractory to standard immunosuppr essive therapy remains a major cause of morbidity and mortality after allog eneic bone marrow transplantation (BMT), Thalidomide may be effective in so me patients with high-risk or refractory chronic GVHD. We report a single-i nstitution study of thalidomide in 37 BMT patients with extensive chronic G VHD refractory to standard immunosuppressive therapy. Acute GVHD occurred i n 34 (91%) of patients and evolved progressively into chronic GVHD in 23 (6 2%) patients. Thalidomide was added to standard immunosuppressive therapy a median of 11 months (range 0-105 months) after the diagnosis of chronic GV HD. Fourteen of 37 (38%) patients responded after introduction of thalidomi de (one complete, 13 partial). Ten of 21 (46%) children and four of 16 (25% ) adults responded. Responses were seen in eight of 17 (47%) recipients of related donor marrow and six of 23 (30%) recipients of unrelated donor marr ow. Eight of 23 (34%) patients with progressive onset of chronic GVHD showe d a response. There were no deaths among the responders. The remaining 23 p atients (62%) did not respond and of these only two survive, one with progr essive scleroderma, and the other with bronchiolitis obliterans, Chronic GV HD with associated infection (most commonly disseminated fungal infection) was a major contributor to mortality in all cases. Overall, after initiatio n of thalidomide, the 2-year Kaplan-Meier survival was 41% (95% C,I, 24%-59 %), We conclude that thalidomide is a useful and well-tolerated therapy for patients with previously treated refractory chronic GVHD, including those with progressive onset of chronic GVHD, recipients of unrelated donor marro w, and children. Earlier introduction of thalidomide as an adjunct to stand ard immunosuppressive therapy may lead to more frequent responses and possi ble better survival.