Highlighted Research Articles

TET2 and DNMT3A mutations are common in hematologic malignancies and age-related clonal hematopoiesis (ARCH). In the setting of hematopoietic cell transplantation (HCT), the age of grafted cells can differ from the recipient’s age by decades. This creates an opportunity to dissect the contributions of hematopoietic cell-intrinsic versus systemic age to the accumulation of ARCH. In a cohort of 144 pediatric long-term HCT survivors, ARCH correlated with older graft age. Separately, ARCH was more prevalent in HCT recipients than in non-transplanted controls, even after correcting for age. The study is the first to demonstrate higher risk and earlier onset of ARCH in pediatric HCT survivors compared to the general population, and it delineates both graft-intrinsic aging and transplantation setting contributions to this effect.See article, p. 110.A prerequisite for CAR T-cell therapy (CART), lymphodepletion results in profound lymphopenia. Here, the authors characterize the immune reconstitution (IR) dynamics in a large cohort of patients with large B-cell lymphoma across three approved commercial CARTs. Nearly half of the patients remained lymphopenic at 1 year, with likely contributions of lymphodepletion intensity among axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel to varied patterns of effector, memory, naïve T-cell, and B-cell recovery. Early NK cell recovery correlated with progression-free and overall survival. These findings highlight the need to mitigate immunosuppression post-CART, and they lay the foundation for exploring whether and how NK cells and other endogenous lymphocyte subsets may contribute to anti-lymphoma CAR T-cell responses.See article, p. 119.