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Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy

CD19-specific chimeric antigen receptor (CAR) T cell therapy has changed the treatment paradigm for pediatric, adolescent and young adult (AYA) patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, data on the associated infectious disease challenges in this patient...

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Autores principales: Maron, Gabriela M., Hijano, Diego R., Epperly, Rebecca, Su, Yin, Tang, Li, Hayden, Randall T., Naik, Swati, Karol, Seth E., Gottschalk, Stephen, Triplett, Brandon M., Talleur, Aimee C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959860/
https://www.ncbi.nlm.nih.gov/pubmed/35356197
http://dx.doi.org/10.3389/fonc.2022.845540
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author Maron, Gabriela M.
Hijano, Diego R.
Epperly, Rebecca
Su, Yin
Tang, Li
Hayden, Randall T.
Naik, Swati
Karol, Seth E.
Gottschalk, Stephen
Triplett, Brandon M.
Talleur, Aimee C.
author_facet Maron, Gabriela M.
Hijano, Diego R.
Epperly, Rebecca
Su, Yin
Tang, Li
Hayden, Randall T.
Naik, Swati
Karol, Seth E.
Gottschalk, Stephen
Triplett, Brandon M.
Talleur, Aimee C.
author_sort Maron, Gabriela M.
collection PubMed
description CD19-specific chimeric antigen receptor (CAR) T cell therapy has changed the treatment paradigm for pediatric, adolescent and young adult (AYA) patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, data on the associated infectious disease challenges in this patient population are scarce. Knowledge of infections presenting during treatment, and associated risk factors, is critical for pediatric cellular therapy and infectious disease specialists as we seek to formulate effective anti-infective prophylaxis, infection monitoring schemas, and empiric therapy regimens. In this work we describe our institutional experience in a cohort of 38 pediatric and AYA patients with CD19-positive malignancy treated with lymphodepleting chemotherapy (fludarabine/cyclophosphamide) followed by a single infusion of CD19-CAR T cells (total infusions, n=39), including tisagenlecleucel (n=19; CD19/4-1BB) or on an institutional clinical trial (n=20; CD19/4-1BB; NCT03573700). We demonstrate that infections were common in the 90 days post CAR T cells, with 19 (50%) patients experiencing a total of 35 infections. Most of these (73.7%) occurred early post infusion (day 0 to 28; infection density of 2.36 per 100 patient days-at-risk) compared to late post infusion (day 29 to 90; infection density 0.98 per 100 patient days-at-risk), respectively. Bacterial infections were more frequent early after CAR T cell therapy, with a predominance of bacterial blood stream infections. Viral infections occurred throughout the post infusion period and included primarily systemic reactivations and gastrointestinal pathogens. Fungal infections were rare. Pre-infusion disease burden, intensity of bridging chemotherapy, lymphopenia post lymphodepleting chemotherapy/CAR T cell infusion and development of CAR-associated hemophagocytic lymphohistiocytosis (carHLH) were all significantly associated with either infection density or time to first infection post CAR T cell infusion. A subset of patients (n=6) had subsequent CAR T cell reinfusion and did not appear to have increased risk of infectious complications. Our experience highlights the risk of infections after CD19-CAR T cell therapy, and the need for continued investigation of infectious outcomes as we seek to improve surveillance, prophylaxis and treatment algorithms.
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spelling pubmed-89598602022-03-29 Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy Maron, Gabriela M. Hijano, Diego R. Epperly, Rebecca Su, Yin Tang, Li Hayden, Randall T. Naik, Swati Karol, Seth E. Gottschalk, Stephen Triplett, Brandon M. Talleur, Aimee C. Front Oncol Oncology CD19-specific chimeric antigen receptor (CAR) T cell therapy has changed the treatment paradigm for pediatric, adolescent and young adult (AYA) patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, data on the associated infectious disease challenges in this patient population are scarce. Knowledge of infections presenting during treatment, and associated risk factors, is critical for pediatric cellular therapy and infectious disease specialists as we seek to formulate effective anti-infective prophylaxis, infection monitoring schemas, and empiric therapy regimens. In this work we describe our institutional experience in a cohort of 38 pediatric and AYA patients with CD19-positive malignancy treated with lymphodepleting chemotherapy (fludarabine/cyclophosphamide) followed by a single infusion of CD19-CAR T cells (total infusions, n=39), including tisagenlecleucel (n=19; CD19/4-1BB) or on an institutional clinical trial (n=20; CD19/4-1BB; NCT03573700). We demonstrate that infections were common in the 90 days post CAR T cells, with 19 (50%) patients experiencing a total of 35 infections. Most of these (73.7%) occurred early post infusion (day 0 to 28; infection density of 2.36 per 100 patient days-at-risk) compared to late post infusion (day 29 to 90; infection density 0.98 per 100 patient days-at-risk), respectively. Bacterial infections were more frequent early after CAR T cell therapy, with a predominance of bacterial blood stream infections. Viral infections occurred throughout the post infusion period and included primarily systemic reactivations and gastrointestinal pathogens. Fungal infections were rare. Pre-infusion disease burden, intensity of bridging chemotherapy, lymphopenia post lymphodepleting chemotherapy/CAR T cell infusion and development of CAR-associated hemophagocytic lymphohistiocytosis (carHLH) were all significantly associated with either infection density or time to first infection post CAR T cell infusion. A subset of patients (n=6) had subsequent CAR T cell reinfusion and did not appear to have increased risk of infectious complications. Our experience highlights the risk of infections after CD19-CAR T cell therapy, and the need for continued investigation of infectious outcomes as we seek to improve surveillance, prophylaxis and treatment algorithms. Frontiers Media S.A. 2022-03-09 /pmc/articles/PMC8959860/ /pubmed/35356197 http://dx.doi.org/10.3389/fonc.2022.845540 Text en Copyright © 2022 Maron, Hijano, Epperly, Su, Tang, Hayden, Naik, Karol, Gottschalk, Triplett and Talleur https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Maron, Gabriela M.
Hijano, Diego R.
Epperly, Rebecca
Su, Yin
Tang, Li
Hayden, Randall T.
Naik, Swati
Karol, Seth E.
Gottschalk, Stephen
Triplett, Brandon M.
Talleur, Aimee C.
Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy
title Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy
title_full Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy
title_fullStr Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy
title_full_unstemmed Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy
title_short Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy
title_sort infectious complications in pediatric, adolescent and young adult patients undergoing cd19-car t cell therapy
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959860/
https://www.ncbi.nlm.nih.gov/pubmed/35356197
http://dx.doi.org/10.3389/fonc.2022.845540
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