Busulfan, Melphalan, Fludarabine and T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Followed by Post Transplantation Donor Lymphocyte Infusions

Inclusion Criteria:

* Patient must have multiple myeloma that has either relapsed or has high risk cytogenetics.
* Patients with relapsed multiple myeloma following autologous stem cell transplantation must have achieved at least partial response following additional chemotherapy (cohort 1):
* Patients are eligible if relapse occurs with complex/high-risk cytogenetics or occurs with normal cytogenetics but within 15 months following the autologous transplant.
* Patients with high risk cytogenetics at diagnosis must have achieved at least very good partial response following autologous stem cell transplantation (cohort 2):

  * Patients must have complex karyotype, 1q25, del17p, t4;14 and/or t14;16 by FISH and/or del13 by karyotyping.

DONOR: Patients must have a healthy HLA matched or mismatched related or unrelated donor who is willing to receive G-CSF injections and undergo apheresis for PBSC collection, or undergo a marrow harvesting procedure.

1. HLA-matched related and unrelated donors Patients who have an HLA-matched related or unrelated donor are eligible for entry on this protocol. This will include a healthy donor who is genotypically matched at all A, B, C, DRB1 and DQB1 locus, loci, as tested by DNA analysis.
2. HLA- mismatched related and unrelated donors Patients who do not have an HLA-matched donor but have a related or unrelated donor who have one antigen or one allele mismatch at the HLA A, B, C, DRB1 or DQB1 loci; or who have two mismatches, at HLA-DQB1 and at one other locus, will be eligible for entry on this protocol.

The following inclusion criteria are also required:

* Patients should be ≥ 21, \< 73 years old.
* Patients may be of either gender or any ethnic background.
* Patients must have a Karnofsky (adult) or Performance Status ≥ 70%
* Patients must have adequate organ function measured by:

Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 50% and must improve with exercise. Hepatic: \< 3x ULN ALT and ≤ 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.

Renal: serum creatinine \<1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl \> 40 ml/min (measured or calculated/estimated) with dose adjustment of Fludarabine for \<70ml/min.

Pulmonary: asymptomatic or if symptomatic, DLCO \> 50% of predicted (corrected for hemoglobin)

* Each patient must be willing to participate as a research subject and must sign an informed consent form.

Exclusion Criteria:

* Patients achieving \< Partial Response following preceding chemotherapy (cohort 1) or \< Very Good Partial Response following autologous stem cell transplantation (cohort 2).
* Patients with Plasma Cell Leukemia.
* Female patients who are pregnant or breast-feeding
* Active viral, bacterial or fungal infection
* Patient seropositive for HIV-I/II; HTLV -I/II
* Patients who have undergone prior allogeneic hematopoietic stem cell transplantation.
* Patients who have had a previous malignancy that is not in remission.
* Patients with known hypersensitivity to mouse proteins (murine antibodies in ISOLEX) if receiving SBA-E- bone marrow, or chicken egg products.