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