Donor Peripheral Stem Cell Transplant, Fludarabine, and Busulfan 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.

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