Donor Peripheral Stem Cell Transplant, Fludarabine, and Busulfan in Treating Patients With Hematologic Cancers

Giving chemotherapy drugs, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It also stops 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 mycophenolate mofetil before and after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of giving donor peripheral stem cell transplant together with fludarabine and busulfan and to see how well it works in treating patients with hematologic cancers.

OUTLINE:

* Conditioning regimen: Patients receive busulfan IV over 3 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
* Allogeneic peripheral blood stem cell transplant (PBSC): Patients undergo allogeneic PBSC on day 0.
* Immunosuppressive therapy/graft-versus-host disease (GVHD) prophylaxis: Patients achieve100% donor T-cell chimerism on day 30 without disease recurrence, and cyclosporine A (CSA) IV continuously over 24 hours or orally every 12 hours on days -1 to 60 followed by a taper until day 100 and oral mycophenolate mofetil (MMF) once every 12 hours on days 1-40, in the absence of ≥ grade 2 GVHD.

Patients with recurrent disease or \< 100% donor T-cell chimerism (on day 30) undergo a 12-day CSA and MMF taper followed by escalating doses of previously collected donor leukocyte infusion every 4 weeks until 100% donor T-cell chimerism or disease regression, in the absence of ≥ grade 2 GVHD.

After completion of study treatment, patients are followed periodically.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosed with any of the following:

  * Acute myeloid leukemia (AML), meeting 1 of the following criteria:

    * Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
    * In first complete remission (CR1) with poor-risk cytogenetics, antecedent hematological disease (i.e., myelodysplasia), or treatment-related leukemia
  * Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

    * Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
    * CR1 with Philadelphia chromosome or poor-risk cytogenetics
  * Chronic myelogenous leukemia (CML), meeting the following criteria:

    * First or second chronic phase

      * Must be documented disease progression after imatinib mesylate therapy OR documented lack of cytogenetic response 6 months post-imatinib mesylate initiation OR imatinib mesylate intolerance
  * Chronic lymphocytic leukemia (CLL), meeting the following criteria:

    * Recurrent disease after fludarabine-based therapy

      * Must have chemosensitive disease at the time of relapse, defined as greater than 50% reduction of WBC and lymphadenopathy
  * Recurrent Hodgkin lymphoma, recurrent non-Hodgkin lymphoma (NHL) (low-, intermediate-, or high-grade disease\*), or transformed NHL, meeting 1 of the following criteria:

    * Received prior autologous transplantation and cytoreductive therapy at the time of relapse to achieve complete remission (CR) or CR/unconfirmed (CRu) as defined by the International Workshop
    * Relapsed disease that required more than 2 salvage regimens to achieve CR or CRu
  * Recurrent multiple myeloma, meeting the following criteria:

    * Must have received prior autologous transplantation and demonstrate chemosensitivity at the time of relapse, defined as greater than 50% reduction of M-component or plasma-cell marrow infiltration
  * Myelodysplastic syndrome

    * Refractory anemia (RA)/RA with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD)/refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD-RS), or RA with excess blasts (RAEB) I, meeting the following criteria:

      * Must be transfusion-dependent and have an IPSS score ≥ 1.5, based on WHO criteria
      * No RAEB II or del(5q)
* No uncontrolled CNS metastases
* 5-6/6 HLA-matched sibling or 9-10/10 matched unrelated donor (both patient and donor) available

PATIENT CHARACTERISTICS:

* Karnofsky performance status ≥ 50%
* Serum creatinine ≤ 2 mg/dL
* Not pregnant
* Fertile patients must use effective contraception
* 50 years of age or older

  * Patients 18-50 years of age are eligible if meeting 1 of the following criteria:

    * Have a preexisting medical condition
    * Received prior therapy (i.e., autologous transplantation) and are considered to be too high risk for conventional myeloablative transplantation
* Must be willing to accept or comprehend irreversible sterility as a side effect of therapy
* No uncontrolled active infection
* No psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
* Cardiac ejection fraction ≥ 30%
* Corrected pulmonary-diffusing capacity ≥ 35%
* No serologic evidence of infection with HIV
* No decompensated liver disease with serum bilirubin \> 2.0 mg/dL

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics