Fludarabine and Radiation Therapy in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Phase or Accelerated Phase Chronic Myelogenous Leukemia

DISEASE CHARACTERISTICS:

• Diagnosis of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia, meeting 1 of the following criteria:

  • Chronic phase

    • Ph+ by cytogenetics or fluorescent in situ hybridization (FISH) assay

  • Accelerated phase, meeting any of the following criteria:

    • More than 10% but < 30% myeloblasts and promyelocytes in marrow or peripheral blood
    • Any additional clonal cytogenetic abnormalities
    • Increasing splenomegaly
    • Extramedullary tumor
    • WBC, platelet count, or hematocrit perturbations not controlled by therapy with hydroxyurea, interferon, or imatinib mesylate
    • Persistent unexplained fever or bone pain
• Less than 5% blasts in the marrow at time of transplantation
• Not eligible for OR refused conventional myeloablative allogeneic stem cell transplantation

• Failed OR suboptimal response to prior imatinib mesylate, as defined by 1 of the following:

  • Absence of complete hematologic response after > 3 months of treatment with imatinib mesylate

  • Absence of cytogenetic response, as defined by 1 of the following:

    • Absence of any cytogenetic response (< 95% Ph+ or BCR/ABL+ cells by cytogenetic or FISH analysis, respectively) after 6 months of treatment with imatinib mesylate
    • Absence of major cytogenetic response (< 35% Ph+ or BCR/ABL+ cells by cytogenetic or FISH analysis, respectively) after 1 year of treatment with imatinib mesylate
    • Absence of complete cytogenetic response (no Ph+ cells by cytogenetic analysis OR BCR/ABL+ cells within normal limits by FISH analysis) after 18 months of treatment with imatinib mesylate
  • Hematologic evidence of disease progression

  • Cytogenetic evidence of disease progression

    • Increase in Ph+ cells or BCR/ABL+ cells by > 20% with at least 1 month between sequential testing

  • Molecular evidence of disease progression

    • More than 10-fold increase in BCR/ABL mRNA levels by quantitative polymerase chain reaction (Q-PCR) with at least 1 month between 2 sequential tests
  • Experienced adverse events during treatment with imatinib mesylate that precluded further administration of the drug
• No CNS disease refractory to intrathecal chemotherapy

• HLA identical related donor available

  • Phenotypically matched at HLA-A, -B, -C, DRQ1, and DBQ1
• No presence of circulating leukemic blasts by standard pathology

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Karnofsky 70-100% OR
• Lansky 70-100%

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• No fulminant liver failure
• No cirrhosis of the liver with evidence of portal hypertension or bridging fibrosis
• 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

• Renal failure allowed

Cardiovascular

• No symptomatic coronary artery disease
• Ejection fraction ≥ 35%
• No other cardiac failure requiring therapy
• No poorly controlled hypertension (blood pressure ≥ 150/90 mm Hg) on standard medication

Pulmonary

• DLCO ≥ 30%
• Total lung capacity ≥ 30%
• FEV_1 ≥ 30%
• No requirement for continuous supplementary oxygen
• No fungal pneumonia with radiological progression after treatment with amphotericin or mold-active azoles for > 1 month

Other

• Not pregnant or nursing
• Fertile patients must use effective barrier contraception during and for 12 months after completion of study treatment
• HIV negative
• No other disease that severely limits life expectancy
• No other active malignancy except localized nonmelanoma skin cancer
• No nonhematologic malignancy within the past 5 years that is currently in complete remission and has a > 20% risk of disease recurrence except for nonmelanoma skin cancer
• No systemic uncontrolled infection
• No active bacterial or fungal infection unresponsive to medical therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 48 hours since prior imatinib mesylate