TY - JOUR
T1 - Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES)
T2 - a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment
AU - Keller, Michael D.
AU - Hanley, Patrick J.
AU - Chi, Yueh Yun
AU - Aguayo-Hiraldo, Paibel
AU - Dvorak, Christopher C.
AU - Verneris, Michael R.
AU - Kohn, Donald B.
AU - Pai, Sung Yun
AU - Dávila Saldaña, Blachy J.
AU - Hanisch, Benjamin
AU - Quigg, Troy C.
AU - Adams, Roberta H.
AU - Dahlberg, Ann
AU - Chandrakasan, Shanmuganathan
AU - Hasan, Hasibul
AU - Malvar, Jemily
AU - Jensen-Wachspress, Mariah A.
AU - Lazarski, Christopher A.
AU - Sani, Gelina
AU - Idso, John M.
AU - Lang, Haili
AU - Chansky, Pamela
AU - McCann, Chase D.
AU - Tanna, Jay
AU - Abraham, Allistair A.
AU - Webb, Jennifer L.
AU - Shibli, Abeer
AU - Keating, Amy K.
AU - Satwani, Prakash
AU - Muranski, Pawel
AU - Hall, Erin
AU - Eckrich, Michael J.
AU - Shereck, Evan
AU - Miller, Holly
AU - Mamcarz, Ewelina
AU - Agarwal, Rajni
AU - De Oliveira, Satiro N.
AU - Vander Lugt, Mark T.
AU - Ebens, Christen L.
AU - Aquino, Victor M.
AU - Bednarski, Jeffrey J.
AU - Chu, Julia
AU - Parikh, Suhag
AU - Whangbo, Jennifer
AU - Lionakis, Michail
AU - Zambidis, Elias T.
AU - Gourdine, Elizabeth
AU - Bollard, Catherine M.
AU - Pulsipher, Michael A.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.
AB - Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.
UR - http://www.scopus.com/inward/record.url?scp=85190654254&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-47057-2
DO - 10.1038/s41467-024-47057-2
M3 - Article
C2 - 38637498
AN - SCOPUS:85190654254
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3258
ER -