Fludarabine and Low-Dose TBI Dose Escalation to Determine the Optimal Regimen for Achieving High Rates Engraftment of Unrelated Donor Peripheral Blood Stem Cell in Patients With Chronic Myeloid Leukemia - A Multi-Center Trial

Inclusion Criteria

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