• Disease-free survival (DFS) > 25% among adult patients at 1 year [ Designated as safety issue: No ]
  
• DFS > 40% among pediatric patients at 1 year [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the 1-year disease-free survival of patients with acute lymphoblastic leukemia in complete remission treated with nonmyeloablative allogeneic peripheral blood stem cell transplantation from HLA-matched unrelated donors.

Secondary

• Determine the day 200 transplant-related mortality in patients treated with this regimen.
• Determine the efficacy of donor lymphocyte infusions (DLI) in patients treated with this regimen.
• Determine the toxicity of DLI in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV on days -4 to -2. Patients undergo total body irradiation on day 0 followed by allogeneic peripheral blood stem cell infusion. Patients also receive oral cyclosporine twice daily on days -3 to 100 with a taper from day 101-177 and oral mycophenolate mofetil 3 times daily on days 0-40 with a taper from day 41-96.

Beginning 1-2 weeks after withdrawal of immunosuppression, patients with no evidence of acute graft-vs-host disease grade 2 or greater and no morphological disease progression may receive up to 3 donor lymphocyte infusions (DLI) IV over 30 minutes.

Patients are followed monthly for 4 months, at 6, 12, 18, and 24 months, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 30 patients (20 adults and 10 children) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of adult or pediatric acute lymphoblastic leukemia (ALL)

  • Age 50 to 75 with high-risk disease in complete remission (CR)1 OR disease in CR2 or greater

  • Age 18 to 49 with high-risk disease in CR1 OR disease in CR2 or greater and ineligible for or refused conventional allogeneic transplantation

    • CR is defined as:

      • Less than 5% blasts by morphology on a bone marrow biopsy and absence of peripheral blasts
    • High-risk adult ALL in CR1 defined as 1 or more of the following:

= 30 years of age or over

• Non-T-cell phenotype
• Cytogenetic abnormalities (e.g., t(9;22), t(4;11), trisomy 8, or monosomy 7)

• Failure to achieve CR after 4 weeks of induction chemotherapy

  • Under 18 years of age with high-risk disease in CR1 OR disease in CR2 or greater and ineligible for conventional allogeneic transplantation

    • High-risk pediatric ALL in CR1 defined as 1 or more of the following:
• Cytogenic abnormalities (e.g., t(9;22) with WBC ≥ 25,000/mm3 at diagnosis, t(4;11) if under 1 year of age or 10 years of age and over, hypodiploidy [< 45 chromosomes])
• Failure to achieve CR after 4 weeks of induction chemotherapy

• Persistent peripheral blasts after 1 week of induction chemotherapy

  • No active CNS disease

  • Must have unrelated donor matched for HLA-DRB1 and -DQB1 by high-resolution typing

    • Single allele disparity allowed for HLA-A, -B, or -C
    • Anti-donor cytotoxic crossmatch negative
    • Patients and donor pairs homozygous at a mismatched allele are considered a 2 allele mismatch (i.e., patient A*0101 and donor A*0102) and therefore not eligible

PATIENT CHARACTERISTICS:

Age:

• See Disease Characteristics
• 75 and under

Performance status:

• Karnofsky 50-100% (17 years of age and over)
• Lansky 40-100% (under 17 years of age)

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• No fulminant liver failure
• No cirrhosis of the liver with evidence of portal hypertension
• No alcoholic hepatitis
• No esophageal varices
• No history of bleeding esophageal varices
• No hepatic encephalopathy
• No uncontrolled hepatic synthetic dysfunction as evidenced by prolongation of PT
• No ascites related to portal hypertension
• No bridging fibrosis
• No bacterial or fungal liver abscess
• No biliary obstruction
• No chronic viral hepatitis AND bilirubin > 3 mg/dL
• No symptomatic biliary disease

Renal:

• Not specified

Cardiovascular:

• Cardiac ejection fraction ≥ 35%* NOTE: *Adults only

Pulmonary:

• No requirement for supplementary continuous oxygen* OR
• DLCO ≥ 40% of predicted* NOTE: *Adults only

Other:

• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study participation

• No active nonhematologic malignancy within the past 5 years except nonmelanoma skin cancer

  • Previous nonhematologic malignancies must have ≤ 20% risk of disease recurrence

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified