Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer
Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer
This clinical trial studies fludarabine phosphate, low-dose total-body irradiation, and donor
 stem cell transplant followed by cyclosporine, mycophenolate mofetil, and donor lymphocyte
 infusion in treating patients with hematopoietic cancer. Giving low doses of chemotherapy,
 such as fludarabine phosphate, and total body irradiation (TBI) before a donor peripheral
 blood stem cell transplant helps stop the growth of cancer cells. It may also keep the
 patient's immune response from rejecting the donor's stem cells. The donated stem cells may
 replace the patient's immune cells and help destroy any remaining cancer cells
 (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte
 infusion) after the transplant may help increase this effect. Sometimes the transplanted
 cells from a donor can also make an immune response against the body's normal cells. Giving
 cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PRIMARY OBJECTIVES:

 I. To estimate the risk of graft rejection associated with the addition of fludarabine
 (fludarabine phosphate) to a non-myeloablative conditioning regimen for patients with
 malignant diseases treatable by allogeneic stem cell transplantation and compare this rate to
 that observed among patients previously treated without fludarabine.

 II. To estimate the rate of grade acute II/IV graft-vs-host disease (GVHD) and chronic GVHD
 in patients treated with low-dose total-body irradiation (TBI), fludarabine, peripheral blood
 stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.

 OUTLINE:

 CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days - 4
 to -2 and undergo low-dose TBI on day 0. (Note: Patients who have had an autologous
 transplant within 90 days prior to day 0 will not receive fludarabine phosphate.)

 PBSC INFUSION: Patients undergo allogeneic PBSC transplant on day 0.

 IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to
 35 with a taper to day 56. Patients receive mycophenolate mofetil PO BID on days 0-27.

 POST TRANSPLANT DONOR LYMPHOCYTE INFUSION (DLI): Patients with stable mixed chimerism on day
 56, and without evidence of GVHD, undergo DLI IV over 30 minutes on day 65. Patients without
 a complete response, full donor chimerism, and GVHD after 2 months undergo further DLI at
 higher cell numbers. Up to 6 DLIs may be given 65 days apart.

 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 < 75 years with non-Hodgkin lymphoma (NHL), chronic
 lymphocytic leukemia (CLL) and multiple myeloma who are not eligible for a curative
 autologous transplantation or who have failed prior autologous transplantation;
 patients with NHL and CLL must have failed prior therapy with an alkylating agent
 and/or fludarabine, or be at high risk of relapse; patients with multiple myeloma must
 have stage II or III disease and received prior chemotherapy

 -  Patients < 50 years of age with NHL, CLL or multiple myeloma at high risk of regimen
 related toxicity through prior autologous transplant or through pre-existing medical
 conditions

 -  Patients < 75 years of age with other malignant 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; the following diseases are the likely candidates:

 -  Myelodysplastic syndromes

 -  Myeloproliferative syndromes

 -  Acute Leukemia with < 10% blasts

 -  Amyloidosis

 -  Hodgkin's disease

 -  Renal cell carcinoma

 -  Patients with other malignancies declining standard allografts may be approved for
 transplant following presentation and approval by the Fred Hutchinson Cancer Research
 Center (FHCRC) chimerism group

 -  DONOR:

 -  Human leukocyte antigen (HLA) genotypically or phenotypically identical related
 donor

 -  Donor must consent to granulocyte colony-stimulating factor (G-CSF)
 administration and leukopheresis

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

 -  Age < 75 years

 Exclusion Criteria:

 -  Eligible for a high-priority curative autologous transplant

 -  Patients with rapidly progressive aggressive NHL unless in minimal disease state

 -  Active 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 who are human immunodeficiency virus (HIV) positive

 -  Cardiac ejection fraction < 40%

 -  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

 -  Patients with renal failure are eligible, however patients with renal compromise
 (serum creatinine greater than 2.0) will likely have further compromise in renal
 function and may require hemodialysis (which may be permanent) due to the need to
 maintain adequate serum cyclosporine levels

 -  DONOR:

 -  Identical twin

 -  Age less than 12 years

 -  Pregnancy

 -  Infection with HIV

 -  Inability to achieve adequate venous access

 -  Known allergy to G-CSF

 -  Current serious systemic illness