CHICAGO--Donor lymphocyte infusion is proving to be a potent treatment for chronic myelogenous leukemia (CML) patients who relapse after allogeneic bone marrow transplant (BMT). It also may improve the overall outcome of CML patients after transplantation, said William Drobyski, MD, at the sixth annual Malnati Symposium in the Clinical Sciences, sponsored by Northwestern University School of Medicine.
"Donor lymphocyte infusion is a powerful form of adoptive immunotherapy that is able to eradicate multiple logs of leukemia cells," said Dr. Drobyski, associate professor of medicine, Medical College of Wisconsin, Milwaukee. However, the treatment has been most effective in patients with CML. "Response in these patients has been durable and may be potentially curable," he added.
Chronic myelogenous leukemia patients who are treated early in the course of their disease, ie, when they are in cytogenic relapse or in the stable chronic phase, respond much more readily to donor lymphocyte infusion than do individuals with more advanced phases of CML.
The response also appears to be evolutionary, taking time to develop, Dr. Drobyski said. "In our experience at the Medical College of Wisconsin, the median time to cytogenic remission for CML patients treated with donor lymphocyte infusion typically is 4 months; the time to molecular remission is 8 months."
Because remission takes time to evolve and an aggressive disease state fails to respond to this form of treatment, "it appears that the clinical efficacy of donor lymphocyte infusion requires that the tumor cell population not be growing so rapidly that it overwhelms any antileukemia response of the transplant," he said.
The question for Dr. Drobyski, nevertheless, is not whether donor lymphocyte infusion can salvage a few patients who have relapsed. It is whether the procedure may improve the overall outcome of patients undergoing BMT for CML, thus prolonging remission and potentially eradicating the disease.
Dr. Drobyski began testing this hypothesis by combining donor lymphocyte infusion with a T-cell depleted BMT graft. A total of 21 patients with CML in primary phase received human leukocyte antigen (HLA) identical bone marrow grafts at the Medical College of Wisconsin between 1988 and 1996.