RATIONALE: Vaccines made from a patient's white blood cells (dendritic cells) and a specific leukemia antigen (Wilms tumor antigen-1) may induce an effective immune response to kill residual leukemic cells and/or prevent leukemia relapse.

PURPOSE: This phase I/II trial is studying the feasibility, safety and efficacy of intradermal mRNA-transfected dendritic cell vaccination therapy in patients with acute myeloid leukemia.

Autologous dendritic cell (DC) vaccination is a promising strategy for adjuvant cancer therapy in the setting of minimal residual disease (MRD). We performed a phase I/II trial in patients with acute myeloid leukemia (AML) where patients received intradermal injections of autologous DC loaded with mRNA coding for the Wilms' tumor protein (WT1). WT1 is highly overexpressed in leukemia and the level of WT1 RNA in peripheral blood is a useful biomarker for molecular diagnosis en follow-up in the MRD setting. We want to prospectively monitor WT1 RNA expression in the peripheral blood of vaccinated and non-vaccinated AML patients in order to evaluate its predictive value as a biomarker for relapse and to assess the clinical efficacy of DC vaccination in acute myeloid leukemia patients. We believe, on the basis of already available evidence, that the use of WT1 both as a target for immunotherapy as well as a biomarker not holds promise to assess the efficacy of new experimental therapeutic interventions such as DC vaccination.

Inclusion Criteria:

1. Tumor type: Acute Myeloid Leukemia (AML) according to the WHO criteria (ea at least 20% blasts in the marrow). All FAB subtypes except M3. Patients with Myelodysplastic Syndrome, category of Refractory Anemia with Excess Blasts (RAEB): RAEB I (WHO: medullary blast count ≤ 10% and a peripheral blast count ≤ 5%) and RAEB II (WHO: medullary blast count > 10% and/or > 5% peripheral blasts) can be included in the study in absence of other non-experimental treatment modalities.

2. Extent of disease: remission (partial or complete) or smouldering course. Complete remission (CR) is defined as no blasts in the peripheral blood and no more than 5% blasts in the bone marrow. This definition is related to the hematological remission if it is not specified. Partial remission (PR) is defined as a decrease of at least 50% in the percentage of blasts to 5 to 25% in the bone marrow aspirate. Smouldering course is defined as a relatively low marrow blast count and slowly progressive disease.

3. Overexpression of WT1 RNA (>50 copies of WT1 per 1000 copies ABL in bone marrow or >2 copy/1000 copies ABL in peripheral blood) as assessed by quantitative RT-PCR at the time of presentation.

4. Prior treatments : Patients must have received at least one prior antileukemic chemotherapeutic regimen and must be more than 1 month past the last treatment and/or 6 months past allogeneic/autologous stem cell transplantation.

5. Age: ≥ 18 years

6. High risk of relapse because of (and/or)

   • Age > 60 years (if <60 y, no sibling allotransplant donor available)
   • Poor risk cytogenetic or molecular markers at presentation
   • Hyperleukocytosis at presentation
   • Second complete remission after relapse

7. Performance status: WHO PS grade 0-1 (Appendix B)

8. Objectively assessable parameters of life expectancy: more than 3 months

9. Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV

10. No concomitant use of immunosuppressive drugs

11. Adequate renal and liver function, i.e. creatinin and bilirubin = 1.2 times the upper limit of normal

12. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

13. Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

1. Subjects with concurrent additional malignancy (with exception of Non-melanoma skin cancers and carcinoma in situ of the cervix)
2. Subjects who are pregnant
3. Subjects who have sensitivity to drugs that provide local anesthesia
4. Age < 18 years