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Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy
Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (N = 127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated f...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579267/ https://www.ncbi.nlm.nih.gov/pubmed/34521106 http://dx.doi.org/10.1182/bloodadvances.2021004716 |
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author | Johnsrud, Andrew Craig, Juliana Baird, John Spiegel, Jay Muffly, Lori Zehnder, James Tamaresis, John Negrin, Robert Johnston, Laura Arai, Sally Shizuru, Judith Lowsky, Robert Meyer, Everett Weng, Wen-Kai Shiraz, Parveen Rezvani, Andrew Latchford, Theresa Mackall, Crystal Miklos, David Frank, Matthew Sidana, Surbhi |
author_facet | Johnsrud, Andrew Craig, Juliana Baird, John Spiegel, Jay Muffly, Lori Zehnder, James Tamaresis, John Negrin, Robert Johnston, Laura Arai, Sally Shizuru, Judith Lowsky, Robert Meyer, Everett Weng, Wen-Kai Shiraz, Parveen Rezvani, Andrew Latchford, Theresa Mackall, Crystal Miklos, David Frank, Matthew Sidana, Surbhi |
author_sort | Johnsrud, Andrew |
collection | PubMed |
description | Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (N = 127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated from 2017 through 2020 with axicabtagene ciloleucel (axi-cel; n = 89) or a bispecific CD19/CD22 CAR (n = 38). Twelve (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within the first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8 and 30 (median, 17.5) and thrombosis between days 2 and 91 (median, 29). Bleeding sites included genitourinary, soft tissue, intracranial, gastrointestinal, and pulmonary and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older, had lower baseline platelets (86 × 10(3)/μL vs 178 × 10(3)/μL; P < .01), lower platelet and fibrinogen nadirs , and elevated lactate dehydrogenase. Immune effector cell (IEC)–associated neurotoxicity syndrome (ICANS) grade ≥3 was associated with increased bleeding (50% vs 15%; P = .01), thrombosis (50% vs 16%; P = .04), prothrombin time prolongation, hypofibrinogenemia, and elevated D-dimer. Low pretreatment platelet counts were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding and should be closely monitored, particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR T therapy, including their association with neurotoxicity. |
format | Online Article Text |
id | pubmed-8579267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-85792672021-11-10 Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy Johnsrud, Andrew Craig, Juliana Baird, John Spiegel, Jay Muffly, Lori Zehnder, James Tamaresis, John Negrin, Robert Johnston, Laura Arai, Sally Shizuru, Judith Lowsky, Robert Meyer, Everett Weng, Wen-Kai Shiraz, Parveen Rezvani, Andrew Latchford, Theresa Mackall, Crystal Miklos, David Frank, Matthew Sidana, Surbhi Blood Adv Clinical Trials and Observations Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (N = 127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated from 2017 through 2020 with axicabtagene ciloleucel (axi-cel; n = 89) or a bispecific CD19/CD22 CAR (n = 38). Twelve (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within the first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8 and 30 (median, 17.5) and thrombosis between days 2 and 91 (median, 29). Bleeding sites included genitourinary, soft tissue, intracranial, gastrointestinal, and pulmonary and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older, had lower baseline platelets (86 × 10(3)/μL vs 178 × 10(3)/μL; P < .01), lower platelet and fibrinogen nadirs , and elevated lactate dehydrogenase. Immune effector cell (IEC)–associated neurotoxicity syndrome (ICANS) grade ≥3 was associated with increased bleeding (50% vs 15%; P = .01), thrombosis (50% vs 16%; P = .04), prothrombin time prolongation, hypofibrinogenemia, and elevated D-dimer. Low pretreatment platelet counts were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding and should be closely monitored, particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR T therapy, including their association with neurotoxicity. American Society of Hematology 2021-11-08 /pmc/articles/PMC8579267/ /pubmed/34521106 http://dx.doi.org/10.1182/bloodadvances.2021004716 Text en © 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. |
spellingShingle | Clinical Trials and Observations Johnsrud, Andrew Craig, Juliana Baird, John Spiegel, Jay Muffly, Lori Zehnder, James Tamaresis, John Negrin, Robert Johnston, Laura Arai, Sally Shizuru, Judith Lowsky, Robert Meyer, Everett Weng, Wen-Kai Shiraz, Parveen Rezvani, Andrew Latchford, Theresa Mackall, Crystal Miklos, David Frank, Matthew Sidana, Surbhi Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy |
title | Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy |
title_full | Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy |
title_fullStr | Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy |
title_full_unstemmed | Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy |
title_short | Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy |
title_sort | incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor t-cell therapy |
topic | Clinical Trials and Observations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579267/ https://www.ncbi.nlm.nih.gov/pubmed/34521106 http://dx.doi.org/10.1182/bloodadvances.2021004716 |
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