This trial is studying the side effects and how well giving cyclophosphamide and busulfan followed by donor stem cell transplant works in treating patients with myelofibrosis, acute myeloid leukemia, or myelodysplastic syndrome. Giving chemotherapy, such as cyclophosphamide and busulfan, before a donor stem cell transplant helps stops the growth of cancer cells. It also helps stop 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 tacrolimus and methotrexate after the transplant may stop this from happening

PRIMARY OBJECTIVES:

I. To estimate the incidence of hepatotoxicity with a conditioning regimen of CY (cyclophosphamide)/tBU (busulfan) in patients receiving hematopoietic cell transplant (HCT).

SECONDARY OBJECTIVES:

I. To determine overall and non-relapse mortality at day +200 after HCT.

II. To determine the peak bilirubin levels through day +20 after HCT.

III. To determine the incidence of pulmonary toxicity in the form of idiopathic pulmonary syndrome (IPS).

IV. To determine the rate of graft failure.

V. To determine the time to engraftment.

VI. To determine the rate of relapse.

VII. To determine the incidence and severity of graft-versus-host disease (GVHD).

VIII. To evaluate the pharmacokinetics/dynamics of BU and CY.

X. To evaluate the pharmacogenomics of response, toxicity and pharmacokinetics of CY/tBU.

OUTLINE:

CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV or orally (PO) twice daily on days -1 to 200 with taper on day 56 and methotrexate on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria:

• Idiopathic myelofibrosis (CIMF)
• Myelofibrosis developing with polycythemia vera or essential thrombocythemia
• Acute myeloid leukemia with or without antecedent hematologic disorder, at any disease stage (complete remission, minimal residual disease, or relapsed leukemia)
• Myelodysplastic syndrome of any World Health Organization (WHO) or French-American-British (FAB) category, at any disease stage
• Less than 61 years of age if transplanted from an unrelated donor, or less than 66 years of age if transplanted from a related donor
• Receiving unmanipulated peripheral blood stem cells from an human leukocyte antigen (HLA)-identical or 1-allele-mismatched related or unrelated donor, or receiving G-CSF-stimulated bone marrow if co-enrolled on Fred Hutchinson Cancer Research Center (FHCRC) protocol 2250
• With a Karnofsky Performance score of > 70% at the time of pre-transplant evaluation
• Able to give informed consent (if >= 18 years of age), or with a legal guardian capable of giving consent (if < 18 years of age)
• DONOR: HLA-identical or 1-allele-mismatched related or unrelated donors (by high resolution typing)
• DONOR: Undergoing peripheral blood stem cell harvest or G-CSF-stimulated bone marrow harvest (bone marrow permitted only as part of FHCRC protocol 2250)
• DONOR: In good general health, with a Karnofsky performance score of > 80%
• DONOR: Able to give informed consent (if >= 18 years of age), or with a legal guardian able to give informed consent (if < 18 years of age and donating for a related transplant)

Exclusion Criteria:

• Without an HLA-identical or 1-allele-mismatched related or unrelated donor
• With human immunodeficiency virus (HIV) positivity or active infectious hepatitis
• Receiving a medication known to strongly inhibit enzymes in the CYP450 pathway, and which, in the judgment of the consenting provider, cannot be safely discontinued for the duration of conditioning
• Whose life expectancy is severely limited by diseases other than the hematologic disorder for which they are undergoing HCT (HCT-comorbidity index [CI] > 3)
• Women who are pregnant or lactating
• With known hypersensitivity to BU or CY
• With hepatic dysfunction as evidenced by total bilirubin or AST > 2x the upper limit of normal, or evidence of synthetic dysfunction or cirrhosis
• With impaired renal function, as evidenced by creatinine clearance < 50% of expected, creatinine > 2x the upper limit of normal, or dialysis dependence
• With impaired pulmonary function, as evidenced by pO2 < 70 mm Hg and diffusing capacity of carbon monoxide (DLCO) < 70% predicted or by pO2 < 80 mm Hg and DLCO < 60%, or receiving continuous supplementary oxygen
• With impaired cardiac function, as evidenced by ejection fraction < 35% or active coronary artery disease
• Unable to give informed consent
• DONOR: Deemed unable to undergo stem cell collection, for any reason
• DONOR: HIV-positive, or hepatitis B or C antigen-positive
• DONOR: Women with a positive pregnancy test
• DONOR: Unable to give informed consent (if >= 18 years of age), or without a legal guardian able to give informed consent (if <18 years of age)