Naive T-cell depletion approach results in lower rates of chronic GVHD after transplant
Depletion of naive T cells from peripheral blood stem cell grafts resulted in very low incidence of severe acute and any graft-versus-host disease in three phase 2 clinical trials, according to a study in Journal of Clinical Oncology.
Additionally, researchers observed no apparent excess risk for relapse or nonrelapse mortality among patients with acute leukemia who received the grafts, distinguishing the novel engineering strategy from other hematopoietic stem cell transplant approaches, they wrote.
“This new procedure has now been studied in a fairly large number of patients, appears to be very reliable technically, consistently results in very low serious acute and chronic GVHD, and generally has very good outcomes in patients regardless of age, type of leukemia, transplant center and other relevant variables,” Marie Bleakley, BMBS, PhD, MMSc, pediatric hematologist-oncologist and Gerdin family endowed chair of leukemia research at Fred Hutchinson Cancer Research Center, told Healio.
Rationale and methodology
HSCT most often involves infusing stem cells collected from a donor with other bone marrow and/or blood cells, including unselected T cells. A major disadvantage of this approach, Bleakley said, is its association with high rates of serious and/or chronic GVHD. In their approach, Bleakley and colleagues removed the T cells most likely to cause GVHD (naive T cells) but left the T cells that can protect patients from infection (memory T cells).
The researchers evaluated chronic GVHD and other outcomes of 138 patients (median age, 37 years; range, 1-60; 59% women) with acute leukemia or advanced myelodysplastic syndrome across three phase 2 trials who received naive T-cell-depleted PBSC grafts from HLA-matched related or unrelated donors after conditioning with high- or intermediate-dose total-body irradiation and chemotherapy.
Results after median follow-up for 4 years showed chronic GVHD occurred infrequently with the naive T-cell-depleted grafts, with 3-year cumulative incidence of 7% (95% CI, 2-11) compared with previously reported rates of 30% to 60% among patients who received unmanipulated grafts. Researchers reported a very low rate of moderate chronic GVHD (1%; 95% CI, 0-2) and no severe cases.
Other 3-year results included a chronic GVHD-free RFS rate of 68%, with similar rates across subgroups, an OS rate of 77% (95% CI, 71-85), cumulative relapse incidence of 23% (95% CI, 16-30) and a nonrelapse mortality rate of 8% (95% CI 3-13).
Analysis also revealed low rates of grade 3 (4%; 95% CI, 1-8) and grade 4 (0%) acute GVHD. Grade 2 acute GVHD — mostly stage I upper gastrointestinal GVHD — occurred in 71% (95% CI, 64-79) of patients.
“Although many recipients of naive T-cell-depleted stem cell grafts do develop some relatively mild acute GVHD, this form of acute GVHD is associated with a very substantially reduced risk [for] relapse of leukemia,” Bleakley said. “We interpret this finding as suggesting that infusion of naive T-cell-depleted grafts typically results in just the right amount of GVHD — enough to help prevent relapse, but not enough to cause serious clinical effects.”
Bleakley and colleagues deemed the strategy “promising and widely applicable” for reducing GVHD and called for future work comparing other GVHD reduction strategies in randomized clinical trials.
“The findings from our studies support studying naive T-cell depletion in more patients in controlled trials comparing naive T-cell depletion of stem cell grafts to standard-of-care unmanipulated stem cell grafts and to other promising approaches to GVHD reduction,” Bleakley said.
For more information:
Marie Bleakley, BMBS, PhD, MMSc, can be reached at Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, Seattle, WA 98109; email: firstname.lastname@example.org.