Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematological Cancer

RATIONALE: Giving chemotherapy before a donor bone marrow stem cell transplant helps stop the growth of cancer cells. Chemotherapy and antithymocyte globulin 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 cyclosporine and methotrexate after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving donor stem cell transplant together with busulfan, fludarabine, and antithymocyte globulin works in treating patients with hematological cancer.

OBJECTIVES:

* To investigate whether unrelated donor hematopoietic stem cell transplantation using a nonmyeloablative conditioning regimen comprising busulfan, fludarabine phosphate, and anti-thymocyte globulin can reduce treatment-related mortality in patients with hematologic malignancies.
* To investigate whether this regimen can be sufficiently immunosuppressive to enable engraftment of HLA-matched unrelated hematopoietic stem cells.

OUTLINE: This is a multicenter study.

Prior to receiving the conditioning chemotherapy regimen, all patients with acute leukemia, chronic myelogenous leukemia (CML), and high-risk myelodysplastic syndromes (chronic myelomonocytic leukemia, atypical CML, and refractory anemia with excess blasts) receive one dose of intrathecal (IT) methotrexate. These patients also receive leucovorin calcium IV or orally 4 hours after IT methotrexate and every 6 hours for a total of 8 doses.

* Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -6, anti-thymocyte globulin IV over 4 hours on days -4 to -2.
* Allogeneic bone marrow stem cell transplantation (SCT): Patients undergo allogeneic bone marrow SCT on day 0.
* Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine (CSA) IV over 2-4 hours every 12 hours starting on day -1 and continuing until day 180 (CSA can be given orally every 12 hours once oral medication can be tolerated) and methotrexate IV on days 1, 3 , 6 , and 11.

Once blood counts recover, patients with acute leukemia or CML in blast crisis resume IT methotrexate once every 2 weeks for a total of 3 doses. Patients also receive leucovorin calcium IV or orally 4 hours after IT methotrexate and then every 6 hours for a total of 8 doses.

Patients are followed for at least 10 years after SCT.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of any 1 of the following:

  * Acute leukemia
  * Chronic myelogenous leukemia
  * Myelodysplastic syndromes
* Must have an unrelated donor available who is matched for HLA-A and -B by serology and for DRB1 by molecular typing

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* Bilirubin \< 3.0 mg/dL
* Creatinine \< 2.0 mg/dL
* AST and ALT \< 3 times the upper limit of normal
* Not pregnant or nursing
* Ejection fraction ≥ 45% by MUGA scan or ECHO
* No major illness or organ failure
* No severe psychiatric disorder or mental deficiency that makes compliance with the treatment unlikely and informed consent impossible

PRIOR CONCURRENT THERAPY:

* Not specified