Safety and Efficacy of High-Dose Memory CD45RO+ Donor Lymphocyte Infusion in Pediatric Recipients after Hematopoietic Stem Cell Transplantation

• Published in: Cytotherapy (Oxford, England) Vol. 26; no. 12; pp. 1458 - 1464
• Main Authors: Gasior Kabat, Mercedes, Li, Ying, Galán, Victor, Mozo, Yasmina, Sisinni, Luisa, Bueno-Sánchez, David, Corral, Dolores, Naik, Swati, Echecopar, Carlos, Aguirre-Portolés, Cristina, Al-Akioui-Sanz, Karima, De Paz, Raquel, Marcos, Antonio, Romero, Ana Belén, Talleur, Aimee, Yuste, Víctor Jiménez, Triplett, Brandon, Pérez-Martínez, Antonio
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-12-2024
• Subjects: adoptive T cell therapy; CD45RA+ cell depletion; CD45RO+ donor lymphocytes; donor lymphocyte infusions; T cell immune reconstitution; T cell immune reconstitution; adoptive T cell therapy; CD45RA+ cell depletion; donor lymphocyte infusions; CD45RO+ donor lymphocytes; CD45RO(+) donor lymphocytes; CD45RA(+) cell depletion
• ISSN: 1465-3249; 1477-2566; 1477-2566
• DOI: 10.1016/j.jcyt.2024.07.007

Memory T selected cells (CD45RA-/RO+) as donor lymphocyte infusion are less capable of producing alloreactivity and graft versus host disease (GvHD) compared with naïve T cells. The objective of this study was to evaluate the safety and efficacy of high-dose memory (CD45RA-/RO+) donor lymphocyte infusion (mDLI) after allogeneic hematopoietic cell transplantation (HCT). Indications for mDLI were “as needed” and “as prophylactic regimen.” Sixty-one children diagnosed with malignant (82%) and non-malignant diseases (18%) received 241 mDLIs. Patients received a median of three infusions (range 1‒13) of mDLI with a median infused dose of 1.35 × 107/kg CD45RO+ containing 8.96 × 106/kg CD3+CD45RO+ and 3.81 × 103/kg CD3+CD45RA+. De novo GvHD developed in 7 patients following 4% of the mDLI infusions. Among patients with GvHD before mDLI, this condition worsened following 6 infusions (11%) in the 3 patients with grade II–IV acute GvHD. A decrease in cytomegalovirus viral load followed 65% of mDLI infusions. Two-year overall survival (OS) for the total cohort was 64% (95% CI 57%‒72%). For patients receiving prophylactic mDLI, the two-year non-relapse mortality was 10% (95% CI 9%‒11%). In summary, high-dose mDLI is feasible and safe, with a relatively low risk of severe GvHD even in patients with active GvHD. Importantly, mDLI was associated with positive effects, including enhanced control of CMV viremia.