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

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining bone marrow or peripheral stem cell transplantation with chemotherapy may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus either 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.

Eligibility Criteria:
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