Combination Chemotherapy Plus Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Myeloproliferative Disorders

OBJECTIVES:

• Assess disease free survival in patients with idiopathic myelofibrosis treated with a preparative busulfan/cyclophosphamide regimen followed by allogeneic bone marrow or peripheral blood stem cell transplantation.
• Determine the risk of primary graft failure in these patients.

OUTLINE: Patients receive a preparative regimen consisting of oral busulfan every 6 hours on days -7 through -4 and cyclophosphamide on days -3 and -2. Patients then receive allogeneic bone marrow or peripheral blood stem cells on day 0. Patients registered on protocol FHCRC-1106.00 randomized to stem cell transplant receive unmodified G-CSF-mobilized stem cells from an HLA-identical donor.

Patients receive cyclosporine/methotrexate or tacrolimus/methotrexate as prophylaxis for graft-versus-host disease (GVHD). Patients receiving marrow from unrelated donors are eligible for appropriate GVHD prophylaxis studies.

Patients are followed at 6 and 12 months after transplant.

PROJECTED ACCRUAL: A maximum of 20 patients will be accrued for this study over approximately 3.5 years.

DISEASE CHARACTERISTICS:

• Idiopathic myelofibrosis (IMF) with at least 1 poor prognosis characteristic, including but not limited to:

• Hemoglobin less than 10 g/dL
• Platelet count less than 100,000/mm^3
• Hepatomegaly (i.e., palpable liver edge 5 cm below costal margin)
• Clinical requirement for splenectomy
• Other myeloproliferative disorders in an IMF like myelofibrotic state eligible
• No evidence of leukemic progression, e.g.:

• Greater than 15% peripheral blood blasts
• Fever or bone pain of unknown origin
• Rapidly progressing splenomegaly
• No other causes for myelofibrosis, such as:

• Collagen vascular disorder
• Lymphoma
• Granulomatous infection
• Metastatic carcinoma
• Hairy cell leukemia
• Myelodysplastic syndrome
• No active central nervous system disease
• One of the following donor/patient pairings is required:

• Donor status:

• Genotypic or phenotypic HLA-matched relative

• Maximum patient age of 65
• One antigen HLA-mismatched relative, HLA-matched unrelated donor, or one antigen HLA-mismatched unrelated donor

• Maximum patient age of 55
• Transplant on this protocol allowed for patients registered on protocol FHCRC-1106.00

PATIENT CHARACTERISTICS:

Age:

• 65 and under

Performance status:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2 times normal
• SGPT no greater than 4 times normal

Renal:

• Creatinine no greater than two times normal OR
• Creatinine clearance at least 50%

Cardiovascular:

• Ejection fraction at least 50%
• Cardiac evaluation required if signs or symptoms of coronary artery disease or congestive heart failure

Other:

• HIV negative
• No active infection
• Patients excluded from this protocol are referred to protocol FHCRC-179.05

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified