Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

PRIMARY OBJECTIVE:

I. Determine the incidence and severity of acute graft-versus-host disease (GvHD).

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of intravenous (IV) busulfan including interdose
variability and evaluation of a limited sampling strategy.

II. Determine thymoglobulin (anti-thymocyte globulin) pharmacokinetics.

III. Determine the incidence of donor engraftment.

IV. Determine system toxicities >= grade 3 per Common Terminology Criteria for Adverse
Events (CTCAE) version (v.) 3.

V. Determine the incidence and severity of chronic GvHD.

VI. Determine the incidence of non-relapse mortality at day +100 and at 1 year (yr).

VII. Determine the incidence of relapse.

VIII. Determine relapse-free survival.

IX. Determine the incidence of Epstein-Barr virus (EBV) activation.

OUTLINE:

Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -9 to -6,
busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on
days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic peripheral blood stem
cell (PBSC) transplant on day 0. Patients then receive tacrolimus IV continuously or orally
(PO) every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1,
3, 6, and 11.

After completion of study treatment, patients are followed at 1 year.

Inclusion Criteria:

- Chronic myelogenous leukemia in chronic phase, accelerated phase and treated blast
phase (CP2)

- Acute myeloid leukemia (AML) in remission or early relapse (< 10% marrow blasts)

- Myelodysplastic syndromes (MDS) ( all risk groups)

- Other myeloproliferative disorders

- DONOR: related or unrelated donors matched for human leukocyte antigen (HLA)-A, B, C,
DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or
mismatched for a single HLA-A, B, C, DRB1 or DQB1 allele

- DONOR: donor must consent to peripheral blood stem cell (PBSC) mobilization with
granulocyte colony-stimulating factor (G-CSF) and leukapheresis; related donors will
be collected at Fred Hutchinson Cancer Research Center (FHCRC), while unrelated
donors will be collected through the National Marrow Donor Program (NMDP) or other
donor centers

- DONOR: Age 12-75 yrs

Exclusion Criteria:

- Cardiac insufficiency requiring treatment or symptomatic coronary artery disease

- Hepatic disease, with aspartate aminotransferase (AST) > 2 times normal

- Severe hypoxemia, oxygen partial pressure (pO2) < 70 mm Hg, with decreased diffusion
capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm
Hg with severely decreased DLCO < 60% of predicted

- Impaired renal function (creatinine > 2 times normal or estimated creatinine
clearance < 60 ml/min)

- MALE: ([140 -age in years] x ideal body weight [kg])/72 x serum creatinine (SCr)
(mg/dL)

- FEMALE: .85 x ([140-age in years] x ideal body weight [kg])/72 x SCr (mg/dL)

- Human immunodeficiency virus (HIV)-positive patients due to risk of reactivation or
acceleration of HIV replication

- Female patients who are pregnant or breast feeding

- Life expectancy severely limited by diseases other than malignancy

- DONOR: donors who for any reason are unable to tolerate the mobilization and
leukapheresis procedure

- DONOR: donors who are HIV-positive, or hepatitis B or C antigen-positive

- DONOR: female donors who have a positive pregnancy test