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