• Survival at 18 months [ Designated as safety issue: No ]
  

• 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 ]
  

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.

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