RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation following combination chemotherapy in treating patients with acute myeloid leukemia or myelodysplastic syndrome.

OBJECTIVES: I. Evaluate overall and leukemia-free survival of patients with acute nonlymphocytic leukemia and myelodysplastic syndromes treated with busulfan/cyclophosphamide (low-risk patients) or cytarabine/busulfan/cyclophosphamide (high-risk patients) followed by allogeneic or syngeneic bone marrow transplant. II. Compare the therapeutic effects of these cytoreduction regimens with those reported in the literature for similar patients who undergo syngeneic or allogeneic marrow transplantation following cytoreduction that includes total-body irradiation. III. Evaluate early and late toxicities produced by these chemotherapy regimens.

PROTOCOL OUTLINE: Low-risk patients (those in first CR who achieved CR with 1 cycle of chemotherapy) are treated on Regimen A; high-risk patients (those in second or subsequent remission who required more than 1 cycle of chemotherapy to achieve first CR, those with MDS, or those with current or prior CNS involvement) are treated on Regimens B and C. The following acronyms are used: ARA-C Cytarabine, NSC-63878 BMT Bone Marrow Transplant BU Busulfan, NSC-750 CF Leucovorin calcium, NSC-3590 CTX Cyclophosphamide, NSC-26271 CYSP Cyclosporine, NSC-290193 GVHD Graft-Versus-Host Disease MTX Methotrexate, NSC-740 Regimen A: 2-Drug Cytoreductive Chemotherapy followed by Bone Marrow Transplantation with, as indicated, GVHD Prophylaxis. BU/CTX; followed by allogeneic or syngeneic BMT; with, for allogeneic BMT, CYSP/MTX Regimen B: 3-Drug Cytoreductive Chemotherapy followed by Bone Marrow Transplantation with, as indicated, GVHD Prophylaxis. BU/CTX/ARA-C; followed by allogeneic or syngeneic BMT; with, for allogeneic BMT, CYSP/MTX. Regimen C: CNS Prophylaxis/Therapy. IT MTX/CF (or IT ARA-C if MTX is contraindicated).

PROJECTED ACCRUAL: 40 evaluable patients will be entered over 2.7 years.

Ages Eligible for Study:  up to  60 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• The following hematologic malignancies are eligible: Acute nonlymphocytic leukemia in one of the following categories: In complete remission In early relapse; Newly diagnosed FAB types; M6 and M7
• Myelodysplastic syndromes including: Refractory anemia with excessive blasts; Refractory anemia with excessive blasts in transformation; Chronic myelomonocytic leukemia
• Secondary acute myeloid leukemia
• Transplantation priority given in decreasing order of: First remission; Second remission; Third remission; Early relapse, with priority further reduced for: Refractory response to platelet transfusion; Severe infection within 6 weeks prior to referral; History of major organ pathology or insult (hepatitis, renal damage, pulmonary disease, cystitis, etc.)
• CNS disease allowed but priority status for transplantation lowered
• Sibling or matched related/unrelated donor required; Donor priority as follows: Monozygotic twin; Genotypical or phenotypical HLA-A, -B, -C, and -D match; Match at any 2 loci (A, B, Dr) on the other haplotype
• ABO-compatible donor preferred; Marrow processed to eliminate mismatched erythrocytes if ABO incompatible
• In case of multiple donors, priority is: ABO compatibility; Age over 18; Same sex
• No physiologic, psychologic, or medical contraindication to donation procedure
• No increased anesthetic risk due to pre-existing illness
• No HIV infection

--Prior/Concurrent Therapy--

• See Disease Characteristics

--Patient Characteristics--

• Age: 6 months to 60 years
• Performance status: Not specified
• Life expectancy: No severe limits on life expectancy due to diseases other than leukemia; No preterminal or moribund patients
• Hematopoietic: Not specified
• Hepatic: Bilirubin no greater than 2.0 mg/dl; Transaminases no greater than 3 x normal; No severe hepatic disease
• Renal: Creatinine no greater than 1.5 mg/dl OR Creatinine clearance at least 60 ml/min; No severe renal disease; No history of severe cystitis with CTX
• Cardiovascular: LVEF at least 50%; No symptomatic cardiac disease
• Pulmonary: FEV1 and FVC at last 75% of normal; No severe pulmonary disease
• Other: No evidence of HIV infection; No severe personality disorder or severe mental illness; No condition (such as substance abuse) that would markedly increase the morbidity and mortality of transplantation
• Criteria of hepatic, renal, cardiac, and pulmonary function and mental illness are used only for initial screening of potential candidates; patients who do not meet these criteria may still be eligible at the discretion of the transplant team