Alemtuzumab, Busulfan, and Cyclophosphamide Followed By a Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving chemotherapy drugs, such as busulfan and cyclophosphamide, before a donor stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the best dose of alemtuzumab when given together with busulfan and cyclophosphamide followed by a donor stem cell transplant and to see how well it works in treating patients with hematologic cancer.

OBJECTIVES:

Primary

* Identify the lowest dose of alemtuzumab that is associated with day 180 transplant-related mortality ≤ 45%.

Secondary

* Determine the incidence of life-threatening infection in patients receiving this treatment.
* Determine the incidence of grades III-IV acute graft-vs-host disease (GVHD) in patients receiving this treatment.
* Determine the survival at 1 year in patients receiving this treatment.
* Determine the incidence of disease relapse at 1 year in patients receiving this treatment.
* Determine the incidence of extensive chronic GVHD at 1 year in patients receiving this treatment.
* Determine the incidence of graft failure at day 100 in patients receiving this treatment.

OUTLINE:

* Chemotherapy: Patients receive alemtuzumab IV over 2 hours on days -10 to -6, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV on days -3 and -2.
* Peripheral blood stem cell (PBSC) transplantation: Patients undergo allogeneic filgrastim (G-CSF)-mobilized PBSC transplantation on day 0.
* Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily on days -1 to 50 and methotrexate IV on days 1, 3, 6, and 11.

After completion of study therapy, patients are followed periodically.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Confirmed diagnosis of one of the following:

  * Primary acute myeloid leukemia (AML) meeting any of the following criteria:

    * First complete remission (CR; defined as \< 5% blasts in marrow) with high-risk features as defined by failure to achieve remission by day 21 after induction chemotherapy, or the presence of chromosomal abnormalities involving any of the following:

      * -5/del(5q)
      * -7/del(7q)
      * Inversion 3q
      * Abnormalities of 11q23, 20q, 21q, del(9q),
      * Translocation 6;9
      * Translocation 9;22
      * Abnormalities of 17p
      * Complex karyotype with ≥ 3 abnormalities
    * Second CR or subsequent in remission
    * Refractory or relapsed disease
  * Secondary AML in remission or relapse
  * Chronic myelogenous leukemia (CML) in accelerated or blast phase meeting the following criteria:

    * Accelerated phase is defined by any one of the following:

      * Blasts 10% to 19% of peripheral blood white cells or bone marrow cells
      * Peripheral blood basophils ≥ 20%
      * Persistent thrombocytopenia (\< 100,000/mm³) unrelated to therapy, or persistent thrombocytosis (\> 1,000,000/mm³) unresponsive to therapy
      * Increasing spleen size and increasing WBC count unresponsive to therapy
      * Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase CML)
    * Blast phase is defined by any of the following:

      * Blasts ≥ 20% of peripheral blood white cells or bone marrow cells
      * Extramedullary blast proliferation
      * Large foci or clusters of blasts in bone marrow biopsy
  * Primary myelodysplastic syndromes (MDS) with an IPSS score \> 1.5
  * Secondary MDS with any IPSS score
  * Primary acute lymphoblastic leukemia meeting any of the following criteria:

    * First CR (\< 5% blasts in marrow) with high-risk features as defined by 1 of the following:

      * Failure to achieve remission after first induction chemotherapy
      * Presence of chromosomal abnormalities including hypodiploidy or abnormalities of 11q23 or translocation 9;22
    * Second CR or subsequent in remission
    * Refractory or relapsed disease
* No patients for whom a suitable HLA genotypically identical sibling or fully matched HLA-A, -B, -C, and -DRB1 unrelated donor is available
* No active CNS involvement with disease
* Donors must meet the following criteria:

  * Unrelated volunteer donors who are mismatched for more than one HLA-class I alleles or antigens or for one HLA-class I antigen, but matched by high-resolution typing at HLA-DRB1 and -DQB1, OR who are mismatched for one or more HLA-class II alleles or antigens, but matched by high-resolution typing at HLA-A, -B, and -C

    * No two-antigen mismatch at a single HLA-A, -B, or -C locus
    * No mismatching of class I and class II HLA
    * Matching must be based on results of high-resolution typing at HLA-A, -B, -C, - DRB1, and -DQB1

PATIENT CHARACTERISTICS:

* Karnofsky performance status 50-100%
* No symptomatic coronary artery disease or symptomatic congestive heart failure
* No hepatic disease with transaminases or bilirubin \> 2 times upper limit of normal except for isolated hyperbilirubinemia attributed to Gilbert's syndrome
* No severe hypoxemia with room air P_AO_2 \< 70, supplemental oxygen-dependence, or DLCO \< 60% predicted
* No impaired renal function with creatinine \> 2 times upper limit of normal or creatinine clearance \< 50% normal
* Not HIV seropositive
* Not pregnant or breast-feeding
* Fertile patients must use effective contraception
* No active infections that are untreated or failing to respond to appropriate therapy

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

* See Disease Characteristics

Exclusion criteria:

* Prior allogeneic or autologous bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation using a high-dose total-body irradiation regimen