• Rate of relapse [ Designated as safety issue: No ]
• Incidence of grade II-IV acute graft-versus-host disease (GVHD) [ Designated as safety issue: Yes ]
• Incidence of grade II-IV chronic GVHD [ Designated as safety issue: Yes ]

• Rate of relapse
• Incidence of grade II-IV acute graft-versus-host disease (GVHD)
• Incidence of grade II-IV chronic GVHD

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system 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.

PURPOSE: This phase II trial is studying how well giving low-dose fludarabine and total-body irradiation before donor stem cell transplant works in treating patients with refractory chronic lymphocytic leukemia.

OBJECTIVES:

Primary

• Compare the 18-month survival rate of patients with fludarabine-refractory chronic lymphocytic leukemia treated with nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors with that observed in historical controls.

Secondary

• Compare the rate of relapse in patients treated with this regimen with that of historical controls.
• Determine the incidence of grade 2-4 acute and chronic graft-versus-host disease in patients treated with low-dose total body irradiation, fludarabine, peripheral blood stem cell infusion, and immunosuppression with cyclosporine and mycophenolate mofetil.
• Determine the rate and types of infections in patients treated with this regimen.
• Determine the rate of transplant-related mortality in the first 200 days in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients may receive cytoreductive therapy before beginning treatment.

• Conditioning regimen: Patients receive fludarabine IV on days -4 to -2. Patients then undergo total body irradiation (TBI) on day 0.
• Allogeneic stem cell transplantation: After TBI, patients undergo hematopoietic stem cell infusion on day 0.
• Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 180 (with tapering beginning on day 56 in the absence of graft-versus-host disease [GVHD]). Patients also receive oral mycophenolate mofetil twice daily on days 0-27 (may continue if GVHD occurs).
• Donor lymphocyte infusion (DLI): Post transplant DLI may given on a separate DLI protocol or treatment plan.

After completion of study treatment, patients are followed at 6, 12, and 18 months, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 3 years.

• Drug: cyclosporine
• Drug: fludarabine phosphate
• Drug: mycophenolate mofetil
• Procedure: peripheral blood stem cell transplantation
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) defined by the following criteria:

  • Absolute peripheral lymphocytosis greater than 5,000/mm^3 that persisted for at least 4 weeks
  • Mature lymphocytes with less than 55% cells comprising atypical lymphocytes, prolymphocytes, or lymphoblasts in peripheral blood
  • Normal cellular or hypercellular bone marrow aspirate and biopsy with greater than 30% of the nucleated cells of lymphoid origin
  • Flow cytometric evidence of more than one B-cell marker (CD19, CD20, or CD23) plus CD5 in peripheral blood or bone marrow
• CLL that progresses to prolymphocytic leukemia (PLL) and CLL/small lymphocytic lymphoma is allowed

• Patients with B-Cell CLL or PLL meeting the following criteria:

  • Failure to meet NCI Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog [e.g., cladribine or pentostatin]) or disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
  • Failed FCR combination chemotherapy at any time point
  • De novo of acquired "17p deletion" cytogenetic abnormality

• Availability of a suitable HLA-matched related donor

  • Related donor who is phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1
  • No identical twins
• No active CNS involvement

PATIENT CHARACTERISTICS:

Age

• 21 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• No chronic viral hepatitis with total serum bilirubin > 3 mg/dL
• No alcoholic hepatitis
• No bacterial or fungal liver abscess
• No ascites related to portal hypertension
• No cirrhosis with evidence of portal hypertension
• No uncorrectable hepatic synthetic dysfunction as evidenced by PT prolongation
• No fulminant liver failure
• No hepatic encephalopathy
• No biliary obstruction
• No symptomatic biliary disease

Renal

• Not specified

Cardiovascular

• Cardiac ejection fraction at least 40%
• No poorly controlled hypertension despite antihypertensive therapy

Pulmonary

• DLCO at least 40%
• Total lung capacity at least 40%
• FEV1 at least 40%
• No requirement for continuous supplementary oxygen
• No severe deficits in pulmonary function

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study treatment
• No esophageal varices OR history of bleeding esophageal varices
• HIV negative
• HTLV-1 and HTLV-2 negative
• No active bacterial infection unresponsive to medication
• No fungal infection with radiological progression unresponsive to amphotericin B or active triazole for > 1 month

• No other non-hematologic malignancy within the past 5 years except nonmelanoma skin cancer

  • Patients with a history of cancer more than 5 years ago must have ≤ 20% chance of recurrence

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent growth factors during mycophenolate mofetil administration

Chemotherapy

• See Disease Characteristics
• More than 3 weeks since cytotoxic agents for cytoreduction except imatinib mesylate, cytokine therapy, hydroxyurea, chlorambucil, or rituxan

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified