Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

Inclusion Criteria:

• Meets one of the following sets of criteria:

  • Myelodysplastic syndromes (MDS):

    • Disease with high-risk features (found either at diagnosis or before initiation of cytotoxic therapy), defined as one of the following:

      • International prognostic scoring system (IPSS) risk >= intermediate-2
      • Refractory anemia with excess blasts by French-American-British (FAB) classification
      • High-risk cytogenetics (either complex or -7)
    • Less than 10% bone marrow blasts as determined by bone marrow biopsy within the past 4 weeks (reduction in marrow blast percentage may be achieved with chemotherapy or other therapy)
    • Less than 75 years old

  • Acute myeloid leukemia (AML):

    • No FAB M3
    • No acute leukemia following blast transformation of prior chronic myelogenous leukemia or other myeloproliferative disease
    • Patients with preceding MDS or treatment-related AML are eligible
    • Prior central nervous system (CNS) involvement is allowed provided the disease is in remission at transplantation

    • Morphologic complete remission (leukemia-free state) is defined as meeting all of the following criteria:

      • Bone marrow blasts < 5% (as determined by bone marrow within the past 4 weeks), but without requirement for normal peripheral blood counts
      • No extramedullary leukemia
      • No blasts in peripheral blood

    • Achieved complete remission (CR) after no more than 2 courses of induction chemotherapy

      • Patients treated with azacitidine or decitabine who achieve a leukemia-free state are eligible (may have required up to 4 courses of therapy to reach this status)
    • Age 60 to 74 years

• Donors must meet the following criteria:

  • One of the following:

    • HLA-identical sibling (6/6) by serologic typing for class (A, B) and low-resolution molecular typing for class II (DRB1)
    • Matched unrelated donor (8/8) by high-resolution molecular typing at HLA-A, -B, -C, and DRB1
  • No syngeneic donors
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Calculated creatinine clearance ≥ 40 mL/min
• Bilirubin < 2 mg/dL OR bilirubin 2-3 mg/dL provided direct bilirubin is normal
• Aspartate aminotransferase (AST) < 3 times upper limit of normal
• Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease
• Left ventricle ejection fraction (LVEF) >= 30% by echocardiogram (ECHO) or multigated acquisition (MUGA)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled diabetes mellitus or active serious infections
• No known hypersensitivity to E. coli-derived products, azacitidine, or mannitol
• No HIV infection or active hepatitis B or C

• Prior azacitidine or decitabine allowed

  • No patients who progressed from MDS to AML during treatment with azacitidine or decitabine
• At least 4 weeks since prior deoxyribonucleic acid (DNA)-hypomethylating chemotherapy, radiotherapy, and/or surgery

• No more than 2 courses of consolidation therapy before transplantation (for patients with AML)

  • Any consolidation regimen that does not require transplantation can be used
  • No more than 6 months from documentation of morphologic CR to transplantation