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

You may be eligible if

• 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