RATIONALE: Giving chemotherapy before a donor stem cell transplant using stem cells that closely match the patient's stem cells, helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine, tacrolimus, and methotrexate before and after transplant may stop this from happening.

PURPOSE: Natural Killer (NK) cells from the donor's bone marrow may be important in fighting leukemia. Bone marrow donors can be selected based on the type of NK cells they have, specifically the killer immunoglobulin receptor (KIR) type. This study provides information on KIR type from potential donors, which can be used in selecting the bone marrow donor. This phase II trial of unrelated donor stem cell transplant in patients with high risk AML (monosomy 7, -5/5q-, high FLT3-ITD AR, or refractory or relapsed AML) in which KIR typing of the patients and potential donors will be available to the treating transplant physician at the time of donor selection.

OBJECTIVES:

• To define the relationship between the status of donor NK-cell receptor and patient outcomes after killer immunoglobulin-like receptor-incompatible unrelated donor (URD) and umbilical cord blood (UCB) hematopoietic cell transplantation (HCT) in young patients with acute myeloid leukemia with monosomy 7, -5/5q-, high FLT3 internal tandem duplication allelic ratio (High-FLT3-ITD AR), or refractory or relapsed acute myelogenous leukemia.
• To correlate the relationships between factors affecting NK receptor status and clinical events.
• To assess NK-cell development after URD and UCB HCT in patients with poor prognosis AML.
• To evaluate NK-cell reconstitution and receptor-acquisition pattern in these patients.

OUTLINE: This is a multicenter study.

• Preparative regimen: Patients receive 1 of the following regimens:

  • Hematopoietic stem cell transplantation (SCT): Patients receive busulfan IV every 6 hours on days -9 to -6, high-dose cyclophosphamide IV over 1 hour on days -5 to -2, anti-thymocyte globulin IV once or twice daily over 4 hours on days -3 to -1, and methylprednisolone IV on days -3 to -1.
  • Umbilical cord blood (UCB) transplantation: Conditioning regimen, infusion procedures, and post-transplant immunoprophylaxis for patients with an UCB donor are according to institutional guidelines and standards.

• Allogeneic hematopoietic stem cell transplantation (SCT) or umbilical cord blood (UCB) transplant: Patients undergo allogeneic SCT or UCB transplant on day 0.

• Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine or tacrolimus IV or orally beginning on day -2 and continuing until day 50, followed by a taper until week 24. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Blood samples will be collected periodically from both patients and donors for studies of natural killer cells in support of the study objectives.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following:

  • Patients with primary refractory acute myeloid leukemia (AML), defined as ≥ 5% bone marrow blasts after two induction courses of chemotherapy

  • Primary refractory AML, defined as ≥ 5% bone marrow blasts after two induction courses of chemotherapy

  • AML or myelodysplastic syndrome with -5/5q- or monosomy 7 without inv(16)/t(16;16) or t(8;21) cytogenetics or NPM or CEBPα mutations

  • Relapsed AML (≥ 5% bone marrow blasts) who meet the customary WHO criteria for AML

  • AML and high FLT3 internal tandem duplication allelic ratio (high FLT3-ITD AR), defined as > 0.4

  • All cases of therapy-related AML (therapy-related AML is considered high risk)

  • Patients with AML, without inv(16)/t(16;16) or t(8;21), monosomy 7, -5/5q-, NPM, or CEPBα mutations, or high FLT3-ITD AR, but with evidence of residual AML (≥ 0.1%) at the end of Induction I; or if a minimal residual disease (MRD) is not performed, then with > 15% bone marrow blasts by morphology after one induction course of chemotherapy

    • Any flow-based MRD is eligible for AAML05P1 for patients not on AAML1031, whereas patients on AAML1031 must utilize the central lab as per the AAML1031 protocol guidelines

• No Fanconi anemia

• Recipients of unrelated marrow or cord blood are eligible for this study

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) (for patients over 16 years of age) or Lansky PS (for patients 16 and under) 50-100%
• Total bilirubin ≤ 2 mg/dL
• SGOT (AST) or SGPT (ALT) ≤ 2.5 times upper limit of normal
• DLCO ≥ 50% OR a normal chest x-ray and pulse oximetry in patients who are unable to undergo pulmonary function tests
• Shortening fraction ≥ 27% by ECHO
• Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min OR creatinine adjusted according to age
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Patients with proven or suspected bacterial sepsis, pneumonia, or meningitis are eligible provided appropriate therapeutic measures have been initiated to control the presumed or proven infection, and systemic signs are not life-threatening
• No evidence or presence of a fungal infection within the past 30 days

PRIOR CONCURRENT THERAPY:

• Prior chemotherapy, radiotherapy or any antileukemic therapy allowed provided patients meet 1 of the following criteria:

  • Received initial treatment for relapsed AML
  • Patients with primary induction failure or relapse who have already received initial therapy and who may have gone on to have additional therapy prior to receiving protocol stipulated therapy on AAML05P1

• No treatment for fungal infection within the past 30 days

• Concurrent radiotherapy to localized painful lesions allowed

• No other concurrent cancer chemotherapy or immunomodulating agents