S9920 Busulfan Compared With Cyclophosphamide in Patients Undergoing Total-Body Irradiation Plus Peripheral Stem Cell Transplantation for Advanced Myelodysplastic Syndrome or Related Acute Myeloid Leukemia
S9920 Busulfan Compared With Cyclophosphamide in Patients Undergoing Total-Body Irradiation Plus Peripheral Stem Cell Transplantation for Advanced Myelodysplastic Syndrome or Related Acute Myeloid Leukemia
RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were
 destroyed by chemotherapy or radiation therapy used to kill tumor cells. It is not yet known
 if total-body irradiation plus peripheral stem cell transplantation is more effective with
 busulfan or with cyclophosphamide for myelodysplastic syndrome or acute myeloid leukemia.

 PURPOSE: Randomized phase III trial to compare the effectiveness of busulfan with that of
 cyclophosphamide in patients undergoing total-body irradiation plus peripheral stem cell
 transplantation for advanced myelodysplastic syndrome or related acute myeloid leukemia.
OBJECTIVES: I. Compare event free survival after total body irradiation (TBI) plus busulfan
 versus TBI plus cyclophosphamide followed by allogeneic peripheral blood stem cell
 transplantation in patients with advanced myelodysplastic syndrome (MDS) or MDS related acute
 myeloid leukemia. II. Determine the distribution of pharmacokinetic parameters for busulfan
 in those patients randomized to the busulfan treatment arm. III. Investigate the prognostic
 significance for event free survival of prior history of red cell transfusions, cytogenetic
 pattern, and of functional drug resistance at diagnosis in these patients. IV. Estimate the
 frequencies of cytogenetic and genetic changes during disease progression in these patients.

 OUTLINE: This a randomized, multicenter study. Patients are stratified according to age (40
 and under vs 41-55) and diagnosis and International Prognostic Scoring System (IPSS) risk
 group (myelodysplastic syndrome (MDS)/IPSS - intermediate 1 vs MDS/IPSS - intermediate 2 vs
 MDS/IPSS high risk vs MDS related acute myeloid leukemia). Patients are randomized to one of
 two treatment arms. Arm I: Patients receive busulfan IV over 2 hours every 6 hours on days -7
 to -4 for a total of 16 doses. Arm II: Patients receive cyclophosphamide IV over 2 hours on
 days -5 and -4. Patients receive total body irradiation (TBI) twice a day on days -3 to -1;
 peripheral blood stem cell transplantation from genotypically HLA identical sibling on day 0;
 cyclosporine IV every 12 hours on days -1 to 60, and then tapering in the absence of graft
 versus host disease; and methotrexate IV on days 1, 3, 6, and 11. Patients are followed every
 6 months for 5 years.

 PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this
 study over 5 years.
DISEASE CHARACTERISTICS: Cytologically confirmed myelodysplastic syndrome (MDS) Increased
 blasts (i.e., greater than 1 to 30% peripheral blood blasts and/or 5 to 30% bone marrow
 blasts) AND International Prognostic Score intermediate 1, intermediate 2, or high risk
 Refractory anemia with excess blasts OR Refractory anemia with excess blasts in
 transformation (no presence of auer rods as sole criteria) OR Chronic myelomonocytic
 leukemia Greater than 1% blasts in the peripheral blood and/or at least 5% blasts in the
 bone marrow OR MDS related acute myeloid leukemia Arising after documented MDS of at least
 60 days Absolute peripheral blast count no greater than 5,000/mm3 Must have genotypically
 HLA identical sibling donor Must also be enrolled on SWOG-S9910 and SWOG-9007

 PATIENT CHARACTERISTICS: Age: 16 to 55 Performance status: Zubrod 0-2 Life expectancy: Not
 specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not
 specified Other: No prior malignancy within past 5 years except: Adequately treated basal
 cell or squamous cell skin cancer Carcinoma in situ of the cervix Adequately treated stage
 I or II cancer in complete remission HIV negative Not pregnant or nursing Fertile patients
 must use effective contraception

 PRIOR CONCURRENT THERAPY: Biologic therapy: No autologous peripheral stem cell
 transplantation prior to diagnosis of myelodysplastic syndrome (MDS) or MDS related acute
 myeloid leukemia Chemotherapy: No prior chemotherapy for MDS or MDS related acute myeloid
 leukemia except oral chemotherapy to control leukocytosis or thrombocytosis (e.g.,
 hydroxyurea or etoposide) Endocrine therapy: Not specified Radiotherapy: No radiotherapy
 prior to diagnosis of MDS or MDS related acute myeloid leukemia Surgery: Not specified