• Safety, as measured by toxicities according to NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  
• Frequency and severity of graft-versus-host disease [ Designated as safety issue: No ]
  
• Feasibility [ Designated as safety issue: No ]
  

• Development of Wilms' tumor-1-directed immunological response and the relationship between immunological findings and clinical results [ Designated as safety issue: No ]
  
• Complete response rate [ Designated as safety issue: No ]
  
• Event-free and overall survival [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To determine the safety, toxicity, and feasibility of donor-derived dendritic cell vaccination and donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (SCT).
• To determine the frequency and severity of graft-versus-host disease in patients treated with peptide-loaded, donor-derived dendritic cell vaccination and DLI.

Secondary

• To evaluate whether immunologic responses to WT-1-specific peptides can be generated by peptide-loaded, donor-derived dendritic cell vaccination and DLI after allogeneic SCT.
• To evaluate whether clinical responses to WT-1-specific peptides can be generated by peptide-loaded, donor-derived dendritic cell vaccination and DLI after allogeneic SCT.
• To evaluate whether immunologic and/or clinical responses may be associated with the degree of WT-1 expression by malignant cells or pre-existing donor anti-WT-1 immunity.

OUTLINE: This is a non-randomized, pilot study.

Patients receive WT-1 peptide-loaded allogeneic dendritic cell (DC) vaccine subcutaneously and intradermally in weeks 0, 2, 4, 6, 8, and 10. Patients will also receive donor lymphocytes IV over 15-30 minutes 1 hour after WT-1 peptide-loaded allogeneic DC vaccine in weeks 0, 4, and 8 in the absence of graft-versus-host disease.

Patients undergo Delayed Type Hypersensitivity skin tests before starting treatment, and again in months 1, 2, 3, 4, 6, 9, and 12 to check the ability of the patient's immune system to respond to the previously given vaccines. Patients also undergo peripheral blood and bone marrow collection periodically during study. Samples are analyzed to evaluate the impact of vaccine therapy on the immune system (i.e., immune cell function, immune cell targets, and WT-1 expression within cancer cells) by immunohistochemistry, quantitative RT-PCR, ELISPOT assay, and flow cytometry.

After completion of study treatment, patients are followed at 3, 4, 6, 9, and 12 months.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

  • Acute lymphocytic leukemia (ALL), ≤ 25% marrow blasts
  • Acute myelogenous leukemia (AML), ≤ 25% marrow blasts

  • Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

    • Chronic phase or recurrent disease after donor lymphocyte infusion (DLI) or resistant to DLI OR resistant to available abl kinase inhibitors
    • Accelerated phase, < 20% marrow blasts
    • Blastic phase, ≤ 25% marrow blasts
  • Myelodysplastic syndrome (MDS), < 20% marrow blasts

  • Non-Hodgkin lymphoma (NHL), meeting both of the following criteria:

    • Stage IV disease
    • ≤ 25% marrow blasts

• WT-1 expression, confirmed by ≥ 1 of the following criteria:

  • More than 15% of malignant cells react with anti-WT-1 by immunohistochemistry
  • Positive quantitative RT-PCR of WT-1 compared with a negative control
• HLA-A2-positive (heterozygous expression is acceptable)

• Residual* or relapsed disease after undergoing prior HLA-matched 5/6 or 6/6 antigen or 8-10/10 allele related or unrelated allogeneic stem cell transplantation (administered at least 42 days ago)

  • Must have post-transplantation donor engraftment, defined by all of the following:

    • Donor chimerism > 50% (peripheral blood)
    • ANC > 500/mm³ (independent of myeloid growth factors)
    • Platelet count > 20,000/mm³ (independent of transfusion) NOTE: *Minimal residual disease by PCR or flow cytometry allowed in accordance with standard disease-specific diagnostic criteria

• Previous HLA-matched related or unrelated allogeneic donor available to donate cells again

  • 5/6 or 6/6 antigen or 8-10/10 allele matched
  • HLA-A2-positive at one allele (heterozygous expression is acceptable)
• No disease progression deemed unacceptably rapid

• No CNS malignancy*

  • CNS malignancy is defined by any of the following:

    • Demonstration of malignant cells in the CSF in patients with leukemia or MDS as manifested by CSF WBC > 5µL and confirmation of CSF blasts
    • Cranial neuropathies deemed secondary to the underlying malignancy
    • CNS mass lesions deemed secondary to the underlying malignancy NOTE: *A history of CNS involvement without current evidence of CNS malignancy is not an exclusion

PATIENT CHARACTERISTICS:

• See Disease Characteristics
• ECOG performance status 0-3
• Life expectancy ≥ 3 months
• Serum creatinine ≤ 1.5 times upper limit of normal (ULN) based on age or creatinine clearance ≥ 60 mL/min
• Total bilirubin ≤ 2.0 mg/dL
• ALT ≤ 5 times ULN based on age
• No active acute or extensive chronic graft-versus-host disease > grade 1
• No clinically significant systemic illness (e.g., severe unstable infections or organ dysfunction) that, in the opinion of the PI, would likely compromise the patient's ability to tolerate treatment or interfere with study procedures
• No HIV infection
• No HTLV-1 infection
• No active hepatitis B or C infection
• Must be able to comply with protocol requirement as determined by the PI, social worker, and primary team
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior treatment-related and transplant-related toxicity to < grade 2
• At least 2 weeks since prior disease-specific therapy
• At least 2 weeks since prior and no concurrent chemotherapy or radiotherapy
• At least 2 weeks since prior antineoplastic therapy
• At least 4 weeks since prior donor lymphocyte infusion

• At least 4 weeks since prior and no concurrent systemic corticosteroids or other immunosuppressive therapy

  • Topical agents and/or inhaled corticosteroids allowed
• No concurrent craniospinal radiotherapy
• Concurrent therapy or prophylaxis for CNS leukemia or lymphoma (i.e., standard intrathecal chemotherapy) allowed as clinically indicated after approval by the principal investigator (PI) in patients with ALL, AML, and CML in blast crisis
• Concurrent hydroxyurea allowed