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

RATIONALE: Giving total-body irradiation and chemotherapy, such as cyclophosphamide, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of cancer or abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving total-body irradiation together with cyclophosphamide works 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.

Eligibility Criteria:
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