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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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Submitted February 12, 2009
Accepted June 14, 2009
GM-CSF secreting cellular immunotherapy in combination with autologous stem cell transplant (ASCT) as post-remission therapy for acute myeloid leukemia (AML)
Ivan M. Borrello, Hyam I. Levitsky*, Wendy Stock, Dorie Sher, Lu Qin, Daniel J. DeAngelo, Edwin P. Alyea, Richard M. Stone, Lloyd E. Damon, Charles A. Linker, Daniel J. Maslyar, and Kristen M. Hege
Johns Hopkins University, Baltimore, MD, United States
University of Chicago, Chicago, IL, United States
Dana Farber Cancer Institute, Boston, MA, United States
University of California, San Francisco, San Francisco, CA, United States
Cell Genesys, South San Francisco, CA, United States
* Corresponding author; email: hy{at}jhmi.edu.
Preclinical models have demonstrated the efficacy of GM-CSF-secreting cancer immunotherapies (GVAX® platform) accompanied by immunotherapy-primed lymphocytes following ASCT in hematologic malignancies. We conducted a phase 2 study of this combination in adult patients with AML. Immunotherapy consisted of autologous leukemia cells admixed with GM-CSF-secreting K562 cells (K562/GM). "Primed" lymphocytes were collected following a single pre-transplant dose of immunotherapy and re-infused with the stem cell graft. Fifty-four subjects were enrolled, 46 (85%) achieved a complete remission (CR) and 28 (52%) received the pre-transplant immunotherapy. For all patients who achieved CR, the 3-year relapse-free survival (RFS) was 47.4% and overall survival (OS), 57.4%. For the 28 immunotherapy treated patients, the RFS and OS was 61.8% and 73.4%, respectively. Post-treatment induction of delayed-type hypersensitivity (DTH) reactions to autologous leukemia cells was associated with longer 3-year RFS (100% vs. 48%). Minimal residual disease (MRD) was monitored by quantitative analysis of WT1, a leukemia-associated gene. A decrease in WT1 transcripts in blood was noted in 69% of patients following 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 ASCT shows encouraging signals of potential activity in AML (ClinicalTrials.gov: NCT00116467).

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