A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD.

In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.

Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.

You will receive 3 drugs for your GVHD prophylaxis:

Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.

Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.

Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.

Inclusion Criteria:

• Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies
• HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor
• ECOG performance status 0-2
• Adequate organ function
• Able to understand and willing to sign a written informed consent document
• Agrees to practice adequate contraception per study requirements

Exclusion Criteria:

• Pregnant or breastfeeding
• Recipient of prior allogeneic or autologous stem cell transplantation
• Prior abdominal radiation therapy
• HIV-positive on combination antiretroviral therapy
• Seropositive for hepatitis B or C
• Allergies to bortezomib, boron, or mannitol
• Myocardial infarction within last 6 months, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias
• Uncontrolled bacterial, viral or fungal infections
• Seizures or history of seizures
• History of another non-hematologic malignancy unless disease-free for at least 5 years
• Uncontrolled intercurrent illness

One participant signed consent and was enrolled onto study, however, was immediately taken off study because it became evident that the participant needed further therapy and was not ready to proceed to transplant.

All adverse events experienced by participants will be collected from the time of the first dose of study treatment, through the study and until the final study visit. Participants continuing to experience toxicity at the off study visit may be contacted for additional assessments until the toxicity has resolved or is deemed irreversible.Participants will be followed for 1 year after transplantation or until death, whichever occurs first.

AEs grade 3-5 & SAEs whether reported by the participant, discovered during questioning, directly observed, or detected by physical examination, laboratory test or other means, will be recorded in the participant's medical record and on the appropriate study-specific case report forms. Participants removed from study treatment for unacceptable AEs will be followed until resolution or stabilization of the AE. One participant was enrolled but immediately taken off study for alternative therapy.