Although allogeneic hematopoietic cell transplantation can result in a cure for patients with advanced hematologic malignancies, studies show chronic graft-vs-host disease occurs in 30% to 60% of patients receiving unmanipulated grafts, often requires prolonged immunosuppression, and may cause nonrelapse mortality and reduced quality of life.
A series of three prospective phase II clinical trials investigating whether depleting antigen-inexperienced naive T cells (TN) from grafts would reduce rates of chronic graft-vs-host disease has found that the incidence of chronic graft-vs-host disease in patients with leukemia who underwent naive T-cell depletion was very low—just 7%—resulting in a 3-year chronic graft-vs-host disease–free, relapse-free survival of 68%; overall survival was 77%. The study by Marie Bleakley, MD, PhD, and colleagues was published in the Journal of Clinical Oncology.
Marie Bleakley, MD, PhD
From December 2009 to March 2020, the researchers enrolled 145 patients with acute leukemia or advanced myelodysplastic syndrome at one of three centers into one of three phase II trials of TN-depleted donor peripheral blood stem cell (PBSC) allografts. Donor PBSC apheresis’ meeting requirements for cell selection were available for 138 of the patients with acute leukemia, most with acute myeloid leukemia (n = 59) or acute lymphocytic leukemia (n = 64).
The patients received TN-depleted PBSC from HLA-matched related or unrelated donors following conditioning with high- or intermediate-dose total-body radiation and chemotherapy. Tacrolimus, with or without methotrexate or mycophenolate mofetil, was given for graft-vs-host disease prophylaxis. The patients received CD34-selected PBSC and a defined dose of memory T cells depleted of TN. The median follow-up was 4 years. The primary outcome of the analysis of cumulative data from the three trials was chronic graft-vs-host disease.
Rates of Chronic Graft-vs-Host Disease
The researchers found that chronic graft-vs-host disease was very infrequent and mild (3-year cumulative incidence total = 7%, 95% confidence interval [CI] = 2%–11%; moderate = 1%, 95% CI = 0%–2%; severe = 0%). Grade III and IV acute graft-vs-host disease occurred in 4% (95% CI = 1%–8%) and 0%, respectively. The cumulative incidence of grade II acute graft-vs-host disease, which was mostly stage I upper gastrointestinal graft-vs-host disease, was 71% (95% CI = 64%–79%). Recipients of matched related donor and matched unrelated donor grafts had similar rates of grade III acute graft-vs-host disease: 5% (95% CI = 0%–9%) and 4% (95% CI = 0%–9%) and chronic graft-vs-host disease: 7% (95% CI = 2%–13%) and 6% (95% CI = 0%–12%). Overall survival, chronic graft-vs-host disease–free, relapse-free survival, relapse, and nonrelapse mortality were, respectively, 77% (95% CI = 71%–85%), 68% (95% CI = 61%–76%), 23% (95% CI = 16%–30%), and 8% (95% CI = 3%–13%) at 3 years.
“Depletion of TN from PBSC allografts results in very low incidences of severe acute and any chronic [graft-vs-host disease], without apparent excess risks of relapse or nonrelapse mortality, distinguishing this novel graft engineering strategy from other hematopoietic cell transplantation approaches,” concluded the study authors.
According to the study authors, depletion of TN from donor PBSC is a promising and widely applicable strategy for reducing chronic graft-vs-host disease, which warrants the comparison to other graft-vs-host disease reduction strategies in randomized clinical trials.
Disclosure: Funding for this study was provided by the National Institutes of Health, National Cancer Institute, Damon Runyon Cancer Research, Richard Lumsden Foundation, the Leukemia and Lymphoma Society, and Burroughs Wellcome Fund. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.