cGVHD is the most serious and common long-term complication of this allogeneic transplantation, occurring in 30-70% of patients surviving more than 100 days. cGVHD is associated with a high degree of morbidity and mortality and remains a major cause of late death. Initial therapy involves systemic corticosteroids which can contribute to further complications. In cases where steroids are ineffective or poorly tolerated, effective therapeutic options are limited. Anecdotal reports of myeloma patients treated with bortezomib after transplantation have shown improvement in cGVHD. We have begun a trial of bortezomib in patients with steroid-refractory cGVHD. Patients receive 1.6 mg/m2 q wk x 4 followed by one week of rest, for up to six cycles. To date 9 patients have been entered on trial and 5 have completed between 2 and 4 cycles. The treatment has been well tolerated with no grade 3 or higher adverse events (AE). AE have been grade 1-2 nausea (3), grade 1-2 diarrhea (6) grade 1-2 fatigue (4), one grade 2 transient neuropathy has been reported. There have been 3 treatment delays (1 patient) and dose reduction due to decreased hemoglobin and one due to transient neuropathy. Subjective improvement has reported in 6 of the first 8 patients, Improvement in general well-being has been noted as early as the first treatment. Two patients have had improvement in severe long standing sclerotic changes, including the ability to extend fingers that had long been contracted. Average Rodnan scores on 5 patients with sclerosis completing 2 or more cycles of therapy decreased from (31±9.6 to 13.8±7.5) One patient with non-healing suppurating lesions of his lower extremities has shown marked healing, another has significant decrease in chronic diarrhea. Weekly bortezomib for cGVHD appears to be well tolerated and results in early improvement in long standing refractory disease. Our plan is to enroll twenty-five patients to determine if these encouraging findings are sustainable.