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Cell vaccination early after transplant may increase T cells in CLL
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Vaccination with whole leukemia cells shortly after allogeneic hematopoietic stem cell transplantation was associated with increased long-term disease control in a cohort of patients with chronic lymphocytic leukemia, according to results of a prospective trial.
Catherine J. Wu, MD, associate professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, and colleagues conducted the investigation to evaluate whether vaccination can expand the number of leukemia-reactive T cells and, by association, increase the antitumor effect.
Catherine J. Wu
All 22 patients enrolled had advanced CLL; of them, 18 received as many as six vaccines that were initiated 30 to 45 days after receipt of transplant.
Vaccines contained an admixture of irradiated autologous tumor cells and granulocyte-macrophage colony–stimulating factor–secreting bystander cells.
Researchers collected serial patient peripheral blood mononuclear cell samples after transplant.
The median follow-up duration was 2.9 years (range, 1-4).
Among individuals who had been vaccinated, estimated 2-year PFS was 82% (95% CI, 54%–94%) and estimated 2-year OS was 88% (95% CI, 59%–97%).
Researchers reported comparable incidence of cumulative chronic graft-versus-host disease at 2 years between vaccinated patients and historic controls at their center (68% vs. 63%).
Vaccination modestly affected recovering T cell numbers. However, consistent reactions against autologous tumor cells were observed in the CD8 T cells of vaccinated patients. These cells did not react against alloantigen–bearing recipient cells that showed increased secretion of interferon gamma. Moreover, this reaction was dissimilar from the T-cell reaction among individuals who had not been vaccinated.
More specific analysis indicated that 17% (range, 13%-33%) of CD8 T-cell clones isolated from four vaccinated patients reacted against disease-associated antigens. This effect may have been caused by the limitation of bulk tumor-reactive T cells, researchers wrote.
“Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long- term leukemia control following [allogeneic hematopoietic stem cell transplantation],” Wu and colleagues concluded.
Disclosure: The researchers report support from NCI, the National Heart, Lung and Blood Institute, the Damon-Runyon Cancer Research Foundation and other entities.
Perspective
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Peter Emanuel, MD
Because the average age at diagnosis for CLL is now about 71 years, most patients cannot tolerate the toxicities of a traditional allogeneic hematopoietic stem cell transplantation (allo-HSCT). As a result, reduced-intensity conditioning (RIC) regimens have been developed, but these regimens alone have proved insufficient to eradicate CLL. We thus need to rely on graft-versus-leukemia (GVL) activity. The ongoing challenge is to separate GVL from graft-versus-host disease (GVHD). One way is explored in this manuscript, that being to vaccinate with autologous, irradiated leukemia cells in order to expand leukemia-reactive T cells. The authors hope to get a better and more specific GVL effect without exacerbating GVHD.
In this study, 18 of 22 patients received numerous vaccinations early on after allo-HSCT. Only 18% of these 22 patients developed GVHD, whereas 82% showed some evidence of initiation of early post-transplant autologous tumor cell vaccination. Although these are exciting results, it is also important to note several limitations. Fifty-four patients had leukemia cells collected but only 22 made it to the treatment phase, so 32 dropped out for various reasons. Further, the vaccination efforts resulted in only modest improvements thus far. Clearly these are important steps in the right direction, but further work and investigations need to be performed before this is ready for standard utilization in practice.
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