Risk Factors for and the Clinical Impact of Cytomegalovirus and Epstein-Barr Virus Infections in Pediatric Recipients of TCR-α/β– and CD19-Depleted Grafts

Abstract

Alpha/beta T cell and CD19 depletion are used to improve the outcomes of hematopoietic stem cell transplantation (HSCT). We evaluated the burden of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in pediatric patients after this HSCT type. A cohort of 182 patients with malignant (n = 114) or nonmalignant (n = 68) disorders was transplanted from either matched unrelated (n = 124) or haploidentical (n = 58) donors. The cumulative incidence of CMV and EBV viremia were 51% and 33%, respectively. Acute graft-versus-host disease (GVHD) grades II to IV, D-/R+ serology, and malignant HSCT indications were associated with increased risk of CMV viremia. CMV disease developed in 10 patients (6%). The occurrence of CMV viremia was not associated with inferior outcomes. Acute GVHD grade ≥ II was the only factor significantly associated with an increased risk of EBV viremia. Rituximab significantly decreased the rate of EBV reactivation in a subgroup that received a higher B cell dose in the graft. The rate of EBV-associated disease was .5%, and EBV viremia did not affect survival. TCR-α/β and CD19 depletion are associated with a significant rate of CMV viremia that does not affect survival. The hazard of EBV post-transplant lymphoproliferative disease (PTLD) is eliminated by the combination of CD19 depletion and rituximab.

Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion

“…[7][8][9] Through this approach, it is possible to transfer to the recipient not only donor HSCs but also committed hematopoietic progenitors, as well as mature natural killer (NK) and gd T cells, both these lymphocyte subsets being capable of exerting a protective effect against leukemia cell regrowth and life-threatening infections. 10 Initial clinical results in children with nonmalignant disorders who received haplo-HSCT using this new method of selective T-cell depletion 11 and in small series of pediatric patients with malignancies, some of which were given additional post-transplantation immune suppression, 12,13 were promising, as the reported incidence of GVHD was low, whereas immune reconstitution was improved.…”

“…The median time to neutrophil engraftment in the whole study population was 13 days (range, [9][10][11][12][13][14][15][16][17][18][19]; no variable influenced the kinetics of recovery. The median time to platelet engraftment was 11 days (range, [8][9][10][11][12][13][14][15][16][17][18][19][20].…”

“…The median time to neutrophil engraftment in the whole study population was 13 days (range, [9][10][11][12][13][14][15][16][17][18][19]; no variable influenced the kinetics of recovery. The median time to platelet engraftment was 11 days (range, [8][9][10][11][12][13][14][15][16][17][18][19][20]. It was 10 days (range, [8][9][10][11][12][13][14][15][16]) and 12 days (range, [10][11][12][13][14][15][16][17][18][19][20] in patients given a number of CD34 1 cells either above or below the median value infused (P 5 .03).…”

NK Cells and γδT Cells for Relapse Protection after Allogeneic Hematopoietic Cell Transplantation (HCT)

“…Next generation sequencing of the γδTCRs revealed that CMV reactivation post allo-HCT induced a clonal proliferation of distinct γδT cell clones, suggesting a γδTCR-mediated response of γδT cells upon CMV infection ●● [92]. Longitudinal analysis of γδT cells in series of allo-HCT recipients demonstrated that γδT cell numbers are significantly higher in recipients with CMV viraemia as compared to recipients without CMV reactivation [93–95, 91]. Memory-like γδT cell responses are increasingly recognized, but many questions remain, including the driving ligands and other signal-driving γδT cell responses [96].…”

Transplantation of hematopoietic stem cells in the Regional Children’s Clinical Hospital № 1 in Ekaterinburg. Results of work for the period from 2006 to 2016

“…Известно, что частым осложнением ТГСК, особенно гаплоидентичной, является реактива-ция вирусов группы герпеса: цитомегаловируса (ЦМВ), вируса простого герпеса 6-го типа (ВПГ 6-го типа), вируса Эпштейна-Барр (ВЭБ) [10]. По нашим данным, кумулятивная вероятность ре-активации ЦМВ после ТГСК составила 14,8 %, ВЭБ -22,0 %, ВПГ 6-го типа -44,0 % (рис.…”