You have graft-versus-host disease (GVHD). You are being asked to take part in this research study because there has been no improvement with steroid treatment. There is no standard treatment for your situation. This research study will test the safety and effectiveness of VELCADE® in the treatment of acute GVHD that has not responded to steroids or has worsened when the steroid dose was decreased.

A maximum number of 27 patients will be enrolled in this study. GVHD is a serious complication after bone marrow transplantation from another donor. GVHD is caused by certain cells called lymphocytes. Normally these cells make immune reactions that help protect the body from foreign substances that cause infection. Here, these cells attack the normal tissues of the body as if they were foreign substances. This interferes with the normal function of vital organs and results in their damage. In GVHD these cells attack the skin, liver and bowel. GVHD also increases the chances of infection.

VELCADE® is a drug that inhibits certain immune reactions that happen when lymphocytes encounter foreign substances. We are doing this research to determine if VELCADE® may be useful in treating GVHD.

VELCADE® is approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on their last therapy. Its effectiveness is also being tested in other cancers. The dose of the drug being used in this research study is the same as what is used for the treatment of multiple myeloma. It has not been approved by the FDA for use in GVHD. Therefore, using VELCADE® for GVHD is experimental in this research study.

Inclusion Criteria: (All criteria must be met)

1. Patients must have undergone an allogeneic HSCT
2. Clinical or histological evidence of AGVHD

3. Has been treated with a minimum of 2mg/kg of methylprednisolone per day or equivalent dose of steroids and either one of the following:

   1. Has had a minimum of 3 days of steroids including the day of assignment and has progressive disease.
   2. Has had a minimum of 7 days of steroids including the day of assignment and has had no response.
   3. AGVHD progresses at anytime when steroids are tapered to less than 2mg/kg/day of methylprednisolone or its equivalent.
4. Performance status ECOG 0-2
5. Patients must be willing to use contraception if they have childbearing potential
6. Able to give informed consent
7. Patients must be > 18 years of age, with no upper age limit.

Exclusion Criteria: (Any one criteria will exclude patient)

1. Performance status of ECOG >2.
2. >Grade3 peripheral neuropathy at the time of enrollment
3. Patient has a creatinine clearance (calculated or measured) of <30mL/min at the time of enrollment.
4. Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry , any ECG abnormality at Screening has to be documented by the investigator/co-investigator as not medically relevant.
5. Patient has hypersensitivity to bortezomib, boron or mannitol.
6. Female subject is pregnant or breast-feeding.
7. Patient has received other investigational drug within 14 days prior to enrollment.
8. Serious medical or psychiatric illness likely to interfere with participation in this clinical study or to obtain informed consent.