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Infusion of stem cells and specially generated T-cells from same donor improves leukemia survival
Date:2/27/2013

, lead author on the study and a research associate in the Fred Hutch Immunology Program.

The findings support expanding efforts to target WT1 and provide insights into what is necessary to establish potent and persistent T-cell responses in patients, and such second generation studies have recently been initiated at Fred Hutch.

All of the patients, who were treated post-transplant at Seattle Cancer Care Alliance, Fred Hutch's site for patient care, received adoptively transferred infusions of billions of enhanced CD8 cytotoxic T-cell clones. They were considered at high risk of death because they had already relapsed and/or had a poor prognosis due to unfavorable characteristics of their leukemia.

Four of the 11 patients in the trial received infusions of T-cells that targeted WT1 and were generated in the presence of IL-21. One had detectable relapsed disease and entered complete remission shortly after the T-cells were infused. All four survived after T-cell therapy without relapse for more than 30 months without suffering graft-vs.-host-disease and required no additional anti-leukemic treatment, according to the study. GVHD is a major complication of stem cell transplantation.

Among the seven patients who received infused T-cells generated without the presence of IL-21, two showed direct evidence of anti-leukemic activity, including one patient with advanced progressive disease who had a temporary response.

Researchers undertook the clinical trial because relapse remains a leading cause of death after allogeneic hematopoietic cell transplantation for patients with high-risk leukemias. An obstacle to survival is that the beneficial graft-vs.-tumor effect of a transplant can be offset by concurrent GVHD. Interestingly, patients who develop GVHD have reduced relapse rates. This suggests that lymphocytes present in engrafted donor stem cells can cause a concurrent therapeutic graft-vs.-tumor effect. However, because donor stem cells are not sele
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Contact: Dean Forbes
dforbes@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
Source:Eurekalert

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