"Researchers have been attempting to develop vaccines for cancer, including myeloid malignancies, for decades," according to Jeffrey Molldrem, M.D., study presenter. "We believe that the results of this pilot study show that vaccination for acute myelogenous leukemia may be both effective and safe, and further testing should be done in larger numbers of patients."

The phase I study was designed to determine if the PR1 peptide vaccine could elicit T-cell immunity in leukemia patients whose disease had been resistant to treatment. The vaccine, PR1 peptide, is a nine-amino acid HLA A2-restricted peptide derived from proteinase 3.

Nine patients were treated in three groups of three with a weekly injection for three weeks. Each group received 0.25 mg, 0.5 mg or 1.0 mg of PR1 in incomplete Freund's adjuvant to enhance the formation of PR1-immune T-lymphocytes. Patients were also given 75 mcg of GM-CSF as growth factor. Four patients had acute myelogenous leukemia, four had chronic myelogenous leukemia, and one had myelodysplastic syndrome. Bone marrow cells were obtained prior to the first vaccination and three weeks after the last vaccination to assess disease status.

At each escalating dose level, zero of three, one of three, and three of three entered remission, respectively. Two patients with acute myelogenous leukemia died of progressive disease. The four patients in complete remission developed immunity to PR1, and their tolerance to proteinase 3 was reversed.

Previous studies suggested that T-cell immunity to PR1 results in cytogenetic remission in patients with chronic myelogenous leukemia treated with interferon or donor stem cell transplant, whereas leukemia persists in patients whose immune systems do not react to PR1.

To show that the PR1 immune response was responsible for the patients' remissions, the investigators in the current study examined the cells of one patient who was in the fourth relapse of disease. His PR1-immune T cells increased from 0.1 percent to 0.54 percent after the third vaccination.

"Although the number of patients who participated in the trial is small, this is a very important study," said Robert I. Handin, M.D., president of the American Society of Hematology. "Investigators have struggled very hard to develop effective immunotherapy for any malignancy. These results in leukemia are very encouraging and may be an important step forward."