Fludarabine, Total-Body Irradiation, and Donor Stem Cell Transplant Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Chronic Myelogenous Leukemia

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

  • First or second chronic phase

    • Philadelphia chromosome-positive (Ph+) disease by cytogenetics or fluorescent in situ hybridization (FISH)

  • First accelerated phase, meeting any of the following criteria:

    • More than 10% but < 30% myeloblasts and promyelocytes in bone marrow or peripheral blood
    • Any additional clonal cytogenetic abnormalities
    • Increasing splenomegally
    • Extramedullary tumor
    • WBC, platelet count, or hematocrit pertubations not controlled by therapy with hydroxyurea, interferon, or imatininb mesylate
    • Persistent unexplained fever or bone pain

• Less than 5% blasts in marrow at time of transplant

  • No blast crisis
• No other curative therapy exists

• Received prior imatinib mesylate AND meets ≥ 1 of the following criteria:

  • Hematologic evidence of disease progression
  • Lack of complete hematologic response after 3 months of treatment with imatinib mesylate
  • Cytogenetic evidence of disease progression, defined as an increase in Ph+ cells or BCR/ABL-positive (BCR/ABL+) cells of > 25%
  • Lack of complete cytogenetic remission (no Ph+ cells by cytogenetic analysis or BCR/ABL+ cells by FISH) after 1 year of treatment with imatinib mesylate
  • At least 65% Ph+ cells by cytogenetic analysis or BCR/ABL+ cells by FISH after 6 months of treatment with imatinib mesylate
  • Less than 3-log reduction in BCR/ABL mRNA levels by quantitative polymerase chain reaction (Q-PCR) compared to a standard baseline level after 1 year of treatment with imatinib mesylate
  • Molecular evidence of disease progression, defined as > 1 log increase in BCR/ABL mRNA levels by Q-PCR, detected in 2 samples
  • Experienced adverse events with imatinib mesylate treatment that would preclude further administration of the drug
  • Patient refused further treatment with imatinib mesylate despite lack of disease progression
• Refused conventional myeloablative allogeneic stem cell transplantation OR at high risk for regimen-related toxicity due to pre-existing medical conditions (for patients < 50 years of age)

• Unrelated donor available

  • Matched at HLA-A, -B, -C, -DRB1, and -DQB1 by high-resolution typing

    • A single allele* disparity for HLA-A, -B, or -C allowed
  • Negative anti-donor cytotoxic crossmatch
  • Not a marrow donor NOTE: *Patient and donor pairs homozygous at a mismatched allele (e.g., the patient is A*0101 and the donor is A*0201) are considered a two-allele mismatch and are not allowed
• No CNS involvement with disease that is refractory to intrathecal chemotherapy

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Karnofsky 70-100%
• Lanksy 50-100% (for pediatric patients)

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 uncorrectable hepatic synthetic dysfunction evidenced by prolongation of PT
• No ascites related to portal hypertension
• 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

• Ejection fraction ≥ 40%
• No cardiac failure requiring therapy
• No poorly controlled hypertension (i.e., blood pressure ≥ 150/90 mm Hg despite standard medication)

Pulmonary

• DLCO ≥ 35% (corrected)
• No requirement for supplementary continuous oxygen
• Pulmonary nodules allowed at the discretion of the principal investigator

Immunologic

• HIV negative
• No uncontrolled systemic infection
• No fungal infection with radiological progression after treatment with amphotericin B or active triazole for > 1 month

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after completion of study treatment
• No other active malignancy except nonmelanoma skin cancer
• No prior localized malignancy at high risk (≥ 20%) of recurrence

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• See Chemotherapy

Chemotherapy

• See Disease Characteristics

• More than 3 weeks since prior cytotoxic chemotherapy

  • Imatinib mesylate and interferon are not considered cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified