• Presence of donor lymphohematopoietic chimerism in peripheral blood by day 100 post-transplant [ Designated as safety issue: No ]
  
• Non-relapse mortality at day 100 post-transplant [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• To determine the efficacy of a preparative regimen of pentostatin and alemtuzumab plus related or unrelated allogeneic peripheral blood progenitor cell transplantation (PBPCT) in inducing durable donor lymphohematopoietic cell chimerism by 100 days after PBPCT (day +100) in patients with high-risk malignancies and who are at high risk for morbidity and mortality with conventional intensive pre-transplant conditioning regimens.
• To determine the safety of a preparative regimen of pentostatin and alemtuzumab plus related or unrelated allogeneic PBPCT, as measured by the non-relapse mortality at day +100 in these patients.

Secondary

• To determine levels of, viability of, and apoptosis in recipient peripheral blood lymphocytes during and after administration of pentostatin and alemtuzumab, using rare-event flow cytometry and cytofluorimetric assays for apoptosis.
• To determine immunologic reconstitution after allogeneic PBPCT, including levels and 9 repertoire of circulating T and B cells and T cell subsets; levels of immunoglobulins G, A, and M; and levels of IgG subclasses.
• To determine duration and nadir of neutropenia and thrombocytopenia.
• To determine time to neutrophil engraftment (absolute neutrophil count [ANC] > 0.5 x 10^9/L).
• To determine time to platelet engraftment (platelets > 20 x 10^9/L without transfusions).
• To determine incidence and severity of acute graft-vs-host disease (GVHD).
• To determine incidence and extent of chronic GVHD.
• To determine incidence and severity of regimen-related toxicities.
• To determine temporal course and extent of tumor responses (in patients with measurable tumor at time of PBPCT).
• To determine overall and event-free survival (where relapse or treatment-related death is considered an event).
• To determine actuarial probability of relapse and of relapse-free survival .
• To determine amount and duration of red blood cell and platelet transfusion support.
• To determine incidence, types, severity, and outcomes of infections after PBPCT.

OUTLINE: This is a multicenter study.

Patients receive pentostatin IV continuously over 72 hours on days -8 to -6 and alemtuzumab IV over 8 hours on days -5 to -1. Patients then undergo infusion of related or unrelated donor peripheral blood progenitor cells on day 0. Patients also receive cyclosporine IV continuously beginning on day -2 , continuing (IV or orally) until day 100, followed by a taper.

Blood samples are collected periodically for quantitative determination of donor cell chimerism, evaluation of levels of and apoptosis in circulating recipient lymphocytes, and humoral and cellular immune reconstitution.

After completion of study treatment, patients are followed periodically.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Acute myeloid leukemia (AML) in complete or partial remission
  • Acute lymphocytic leukemia (ALL) in complete or partial remission
  • Chronic myeloid leukemia (CML) in first or subsequent chronic phase or accelerated phase
  • Chronic lymphocytic leukemia (CLL) that has recurred or failed after at least one course of front-line therapy
  • Hodgkin lymphoma or non-Hodgkin lymphoma that has failed front-line therapy, is in second or subsequent remission, or is in chemosensitive relapse
  • Multiple myeloma that is in complete or partial remission or in chemosensitive relapse
  • Myelodysplastic syndrome (MDS) classified as intermediate-2 or high-risk according to the International Prognostic Scoring System
  • Metastatic renal cell carcinoma that has failed at least one previous front-line chemotherapy and/or biological therapy regimen and that is radiographically detectable and evaluable

• No AML or ALL in relapse, CML in blast phase/blast crisis, or MDS with greater than 30% marrow involvement (MDS-AML)

  • Patients with these disease characteristics may be considered for this study if complete or partial remissions occur after salvage chemotherapy
• No progressive Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma that is refractory to salvage chemotherapy
• Treatment with at least one previous course of chemotherapy or biological therapy for the malignancy for which allogeneic peripheral blood progenitor cell transplantation (PBPCT) is being considered (i.e., a patient cannot be enrolled on this study for initial treatment of a malignancy)

• Must have a related or unrelated donor who is compatible with the recipient at all HLA-A, -B, -C, and -DRB1 alleles (8/8 HLA match)

  • Must obtain at least 5.0 x 10^6 allogeneic donor CD34+ cells per kg of recipient weight in PBPC product

• Must also meet at least 1 of the following criteria:

  • Age ≥ 50 years
  • Underwent prior transplantation with autologous or allogeneic hematopoietic cells (peripheral blood, bone marrow, or placental blood)
  • High-risk status of hematologic malignancy (i.e., not in first complete remission or first chronic phase)

  • Presence of one or more medical comorbidities that would place the subject at unacceptably high risk of regimen-related mortality after conventional allogeneic hematopoietic stem cell transplantation, such as any of the following:

    • Documented chronic bronchitis or emphysema
    • Decreased cardiac ejection fraction (but with ejection fraction at least 30%)
    • History of coronary artery disease
    • Renal insufficiency (but with creatinine clearance at least 30 mL/min)
    • Hepatic cirrhosis (but with normal hepatic synthetic function)
    • Documented or presumed invasive fungal infection requiring treatment with intravenous antifungal agent(s)
• Ineligible for another clinical therapeutic protocol or standard-of-care treatment that offers higher probability of cure or long-term control of patient's malignancy
• No untreated or progressive CNS involvement by malignancy

PATIENT CHARACTERISTICS:

• See Disease Characteristics
• Karnofsky performance status 50-100%
• Life expectancy ≥ 12 weeks
• No symptomatic ischemic cardiac disease
• DLCO ≥ 35%
• No need for supplemental oxygen
• No severe hepatic cirrhosis with ascites and/or varices
• No hepatic dysfunction associated with abnormal synthetic function (e.g., coagulopathy)
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST or AST ≤ 4 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 12 months after completion of study treatment
• No seropositivity for HIV

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics