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Blood, 27 August 2009, Vol. 114, No. 9, pp. 1736-1745.
Prepublished online as a Blood First Edition Paper on June 25, 2009; DOI 10.1182/blood-2009-02-205278.


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CLINICAL TRIALS AND OBSERVATIONS

Granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML)

Ivan M. Borrello1,*, Hyam I. Levitsky1,*, Wendy Stock2, Dorie Sher2, Lu Qin1, Daniel J. DeAngelo3, Edwin P. Alyea3, Richard M. Stone3, Lloyd E. Damon4, Charles A. Linker4, Daniel J. Maslyar5, and Kristen M. Hege5

1 The Johns Hopkins University, Baltimore, MD; 2 University of Chicago, IL; 3 Dana-Farber Cancer Institute, Boston, MA; 4 University of California, San Francisco; and 5 Cell Genesys, South San Francisco, CA

Preclinical models have demonstrated the efficacy of granulocyte-macrophage colony-stimulating factor-secreting cancer immunotherapies (GVAX platform) accompanied by immunotherapy-primed lymphocytes after autologous stem cell transplantation in hematologic malignancies. We conducted a phase 2 study of this combination in adult patients with acute myeloid leukemia. Immunotherapy consisted of autologous leukemia cells admixed with granulocyte-macrophage colony-stimulating factor-secreting K562 cells. "Primed" lymphocytes were collected after a single pretransplantation dose of immunotherapy and reinfused with the stem cell graft. Fifty-four subjects were enrolled; 46 (85%) achieved a complete remission, and 28 (52%) received the pretransplantation immunotherapy. For all patients who achieved complete remission, the 3-year relapse-free survival (RFS) rate was 47.4% and overall survival was 57.4%. For the 28 immunotherapy-treated patients, the RFS and overall survival rates were 61.8% and 73.4%, respectively. Posttreatment induction of delayed-type hypersensitivity reactions to autologous leukemia cells was associated with longer 3-year RFS rate (100% vs 48%). Minimal residual disease was monitored by quantitative analysis of Wilms tumor-1 (WT1), a leukemia-associated gene. A decrease in WT1 transcripts in blood was noted in 69% of patients after the first immunotherapy dose and was also associated with longer 3-year RFS (61% vs 0%). In conclusion, immunotherapy in combination with primed lymphocytes and autologous stem cell transplantation shows encouraging signals of potential activity in acute myeloid leukemia (ClinicalTrials.gov: NCT00116467 [ClinicalTrials.gov] ).


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