Busulfan, Etoposide, and Total-Body Irradiation in Treating Patients Undergoing Donor Stem Cell or Bone Marrow Transplant for Advanced Hematologic Cancer

OBJECTIVES:

• To determine the efficacy of a preparative regimen comprising dose targeted busulfan, etoposide, and fractionated total-body irradiation followed by allogeneic hematopoietic stem cell or bone marrow transplantation in patients with advanced hematologic malignancies.
• To determine the efficacy of this regimen in patients with acute myeloid leukemia in first remission with unfavorable cytogenetics.
• To evaluate the early and late toxicities of this regimen.

OUTLINE:

• Preparative chemotherapy regimen: Patients receive busulfan IV over 2 hours once every 6 hours on days -14 to -8 for a total of 16 doses and etoposide IV on day -3.* NOTE: *Patients also receive oral or IV dilantin 1-3 times daily on days -18 to -5 for prophylaxis of grand mal seizures.
• Fractionated total-body irradiation (FTBI): Patients undergo FTBI on days -7 to -4 for a total of 10 fractions.
• Allogeneic transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
• Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV or orally on days -1 to 50 followed by a taper to day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil orally or IV over 2 hours twice daily on days 0-27, followed by a taper until day 56.

After completion of study treatment, patients are followed annually for 2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Acute myeloid leukemia (AML)

• Failed remission induction therapy or in relapse beyond second remission
• In first remission with poor risk cytogenetics (e.g., 11q abnormalities, -7, -5, complex abnormalities [i.e., > 3 abnormalities, 6;9 translocation and 3q abnormalities del (7q), del (5q), complex abnormalities ≥ abnormalities, 9q, 20q, 21q, 17q, t(9;21)])
• Acute lymphoblastic leukemia (ALL)

• Failed remission induction therapy or in relapse beyond second remission
• Blastic phase chronic myelogenous leukemia
• Refractory anemia with excess blasts
• Refractory anemia with excess blasts in transformation
• HLA -A, -B, -C, -DR identical sibling donor match available
• No relapse after prior bone marrow transplantation

PATIENT CHARACTERISTICS:

• Cardiac ejection fraction ≥ 50%
• Serum creatinine ≤ 1.2 times upper limit of normal (ULN) or creatinine clearance > 80 mL/min
• Bilirubin ≤ 1.5 times ULN
• AST and ALT < 5 times ULN
• FEV_1 ≥ 50% of predicted normal
• DLCO ≥ 50% of predicted normal
• No psychological or medical condition that would preclude allogeneic transplantation (in the opinion of the treating physician)
• Not pregnant
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 28 days since prior induction or reinduction therapy
• Prior etoposide and busulfan allowed
• No prior radiation therapy that would exclude total-body irradiation