Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

PRIMARY OBJECTIVES:

I. To determine whether mixed hematopoietic chimerism can be safely established using a
non-myeloablative conditioning regimen in patients with non-Hodgkin lymphoma (NHL), chronic
lymphocytic leukemia (CLL) and multiple myeloma.

II. To determine whether mixed chimerism, established with non- myeloablative conditioning
regimens, can be safely converted to full donor hematopoietic chimerism by infusions of donor
lymphocytes (DLI).

OUTLINE:

CYTOREDUCTION: If necessary, patients with advanced malignancies undergo cytoreductive
chemotherapy to reduce tumor size at discretion of primary physician and study investigators.

CONDITIONING REGIMEN: Patients undergo low-dose total-body irradiation followed by allogeneic
peripheral blood stem cell (PBSC) transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine intravenously (IV) twice daily (BID) on days
-1 to 0 and then orally (PO) BID on days 1-35 with taper to day 56. Patients also receive
mycophenolate mofetil PO BID on days 0-27.

POST-TRANSPLANT DLI: Patients with mixed chimerism on day 56 and no evidence of graft-vs-host
disease (GVHD) undergo DLI over 30 minutes on day 65 and may receive up to 3 additional
infusions in the absence of GVHD and disease progression or persistence. Patients who have
not achieved mixed chimerism at day 56 undergo DLI if complete response is not obtained after
a 2 month monitoring period.

After completion of study treatment, patients are followed up at 4, 6, 12, 18, and 24 months
and then annually thereafter.

Inclusion Criteria:

- Patients aged > 49 years and < 66 years with NHL, CLL and multiple myeloma who are not
eligible for autologous transplantation or have failed prior autologous
transplantation; patients with NHL and CLL must have failed prior therapy with an
alkylating agent and/or fludarabine; patients with multiple myeloma must have stage II
or III disease and received prior chemotherapy

- Patients < 50 years of age with NHL, CLL and multiple myeloma at high risk of regimen
related toxicity through prior autologous transplant or through pre-existing chronic
disease affecting kidneys, liver, lungs, and heart will be considered on a case by
case basis and presented to professional clinical counselor (PCC)

- Patients < 66 years of age with other diseases treatable by allogeneic bone marrow
transplant (BMT) whom through pre-existing chronic disease affecting kidneys, liver,
lungs, and heart are considered to be at high risk for regimen related toxicity using
standard high dose regimens; autografting must also be contraindicated in these
patients and they must be approved for this protocol by both PCC and by the principal
investigator; the following diseases are the likely candidates but other less common
diseases may be considered and approved by PCC:

- Myelodysplastic syndromes

- Myeloproliferative syndromes

- Acute leukemia in remission

- Chronic myelogenous leukemia (CML) in 2nd chronic phase

- Hodgkin's disease

- Selected patients with any of the above diagnosis who are (a) older than 65 years and
< 75 years with a Karnofsky score >= 70 and who, apart from age, fulfill eligibility
criteria, or (b) < 66 years but ineligible solely because of renal dysfunction; these
patients must be approved for transplant by both PCC and the principal investigator

- DONOR: Human leukocyte antigen (HLA) genotypically identical sibling

- DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis

- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of
central venous catheter (femoral, subclavian)

- DONOR: Age < 75

Exclusion Criteria:

- Eligible for autologous transplantation

- Patients with rapidly progressive high grade NHL

- History of central nervous system (CNS) involvement with disease

- Fertile men or women unwilling to use contraceptive techniques during and for 12
months following treatment

- Females who are pregnant

- Patients with a creatinine clearance < 50 ml/min

- Cardiac ejection fraction < 40% or cardiac failure requiring therapy

- Severe defects in pulmonary function testing (defects are currently categorized as
mild, moderate and severe) as defined by the pulmonary consultant, or receiving
supplementary continuous oxygen

- Total bilirubin > 2 x the upper limit of normal

- Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic
transaminase (SGOT) 4 x the upper limit of normal

- Karnofsky score < 50

- Patients with poorly controlled hypertension

- DONOR: Identical twin

- DONOR: Age less than 12 years

- DONOR: Pregnancy

- DONOR: Infection with human immunodeficiency virus (HIV)

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to G-CSF

- DONOR: Current serious systemic illness

- DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for
donation as described in the Standard Practice Guidelines