Removing Naïve T Cells is a Promising Strategy for Reducing GVHD

Results reported in the chronic Journal of Clinical Oncology suggest filtering naïve T cells from peripheral blood stem cell transplants may decrease the risk of graft-versus-host-disease. An accompanying editorial says a randomized trial is needed to provide definitive proof.

T cells are problematic when it comes to allogeneic stem cells transplants for blood cancer patients. Non-native T cells in the transplant may attack the patient’s tissues, causing graft-versus-host-disease (GVHD) that is associated with higher mortality. For decades, researchers have tried different T cell “recipes,” eliminating them entirely from the donor stem cells or filtering out subsets. The results have been mixed, with drawbacks such as increase opportunistic infections clouding the prospects of any advantages.

But results reported in a recent issue of the Journal of Clinical Oncology suggest that a strategy for manipulating T cells that could reduce the severity of acute GVHD and the incidence of chronic versions of the condition. An accompanying editorial cautioned, however, that the strategy needs to be compared to others in a clinical trial before it is identified as a preferred method for stem cell transplants.

Marie Bleakley, BMBS, Ph.D., MMSc., of the Fred Hutchinson Cancer Center, and her colleagues combined the results of three phase 2 clinical trials testing whether removing naïve T cells from stem cell transplants would reduce GVHD. Naïve T cells are T cells that have yet been activated by an antigen.

A total of 138 patients with acute leukemia were included in the three trials included in the study by Bleakley and her colleagues. After radiation and chemotherapy treatments, the patients received peripheral blood stem cell transplants to reconstitute their decimated immune system. Peripheral blood stem cell transplants involve collecting stem cells that are circulating in the blood rather than using bone marrow as the source. Before the stem cells were infused into patients, researchers filtered out naïve T cells. Other categories of T cells were in the transplants.The studies had a median follow-up period of four years.

The incidence of chronic GVHD was low and mild among the patients in these trials, according to Bleakley and her co-authors. The three-year cumulative incidence was 7% and none of the cases were severe. Acute GVHD — GVHD that occurs within 100 days of the transplant — was not eliminated: 71% of the patients in the trials had grade 2 acute GVHD (acute GVHD is graded on a scale of 1 to 4 with 1 being the mildest). But severe cases were rare: Grade 3 acute GVHD occurred in 4% of the patients and none had Grade 4.

The results of the trial also show good results on other measures, such as overall survival (77%) and nonrelapse mortality (8%).

The trials included in Bleakley’s and her colleagues’ studies were single-arm phase 2, not randomized trials. But they argued that randomized trials would be unlikely to disprove the low rates of chronic GVHD observed in those studies.

But there are other ways to manipulate and select T cells in stem transplants. In an accompanying editorial, Robert J. Soiffer, MD, of the Dana-Farber Cancer Institute, discussed the results of trials of some of those other strategies and techniques.

“So how should we contextualize the results reported by Bleakley et. al? ” wrote Soiffer. “The concept is intriguing, and the data are excellent but the proof is in the pudding. Only a randomized trial, preferably one incorporating PTCy or ATG/ATLG [other ways of manipulating T cells in stem cell transplants] as one of the comparator arms will determine if they have devised a better mousetrap.”

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