Total-Body Irradiation and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer and Other Diseases

OBJECTIVES:

Primary

• Evaluate the potential efficacy of targeting cyclophosphamide to a metabolic endpoint when given together with total-body irradiation, in terms of day 200 nonrelapse mortality, in patients with hematologic cancer and other diseases who are undergoing allogeneic hematopoietic stem cell transplantation.

Secondary

• Determine the overall survival of patients treated with this regimen.
• Determine the rate of relapse in patients treated with this regimen.
• Determine the occurrence of sinusoidal obstruction syndrome in patients treated with this regimen.
• Determine the occurrence of acute renal failure in these patients.
• Determine the occurrence of respiratory failure in these patients.

OUTLINE:

• Conditioning regimen: Patients undergo total-body irradiation twice daily on days -6 to -4. Patients also receive cyclophosphamide IV over 1 hour on day -3 and then IV at a metabolism-based dose* on day -2.

NOTE: *Patients undergo frequent blood sampling after completion of the first cyclophosphamide infusion for pharmacokinetic studies in order to determine the dose for the second cyclophosphamide infusion.

• Allogeneic stem cell transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
• Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis as per the attending physician, including one of the following regimens: cyclosporine and methotrexate; tacrolimus and methotrexate; tacrolimus and mycophenolate mofetil; or sirolimus, tacrolimus, and methotrexate (as per the GVHD prophylaxis regimen chosen for each patient).

After completion of study treatment, patients are followed periodically for at least 200 days.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of a hematologic cancer or other disease that is unlikely to respond to conventional treatment, including any of the following:

• Chronic myelogenous leukemia
• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Myelodysplastic syndromes
• Lymphoma
• Patients who have bulky tumor mass must not require additional involved-field irradiation
• Planning to undergo conditioning for transplantation at the Seattle Cancer Care Alliance and University of Washington Medical Center
• Must have an HLA-matched donor available

• No donors who are mismatched for > 1 HLA class I antigen or allele
• Negative anti-donor lymphocytotoxic crossmatch

PATIENT CHARACTERISTICS:

• Life expectancy must not be severely limited by diseases other than malignancy
• No moribund patients
• Creatinine ≤ 1.2 mg/dL
• Oxygen saturation on room air ≥ 93%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No HIV positivity
• No cirrhosis
• No hepatic fibrosis with bridging
• No fulminant hepatic failure
• No acute liver injury
• No persistent cholestasis
• No infection requiring systemic antibiotic or antifungal therapy
• No coronary artery disease
• No congestive heart failure requiring therapy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior hematopoietic stem cell transplantation
• No prior radiation therapy to the liver or adjacent organs
• More than 30 days since prior cytoreductive chemotherapy for patients with a large body burden of tumor cells
• No concurrent enrollment in a phase I study