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High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy represents the most advanced immunotherapy against relapsed/refractory B cell malignancies. While cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are distinctive, known CAR T-cell acute adverse events, he...

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Autores principales: Accorsi Buttini, Eugenia, Farina, Mirko, Lorenzi, Luisa, Polverelli, Nicola, Radici, Vera, Morello, Enrico, Colnaghi, Federica, Almici, Camillo, Ferrari, Emilio, Bianchetti, Andrea, Leoni, Alessandro, Re, Federica, Bosio, Katia, Bernardi, Simona, Malagola, Michele, Re, Alessandro, Russo, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897055/
https://www.ncbi.nlm.nih.gov/pubmed/36741006
http://dx.doi.org/10.3389/fonc.2023.1036455
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author Accorsi Buttini, Eugenia
Farina, Mirko
Lorenzi, Luisa
Polverelli, Nicola
Radici, Vera
Morello, Enrico
Colnaghi, Federica
Almici, Camillo
Ferrari, Emilio
Bianchetti, Andrea
Leoni, Alessandro
Re, Federica
Bosio, Katia
Bernardi, Simona
Malagola, Michele
Re, Alessandro
Russo, Domenico
author_facet Accorsi Buttini, Eugenia
Farina, Mirko
Lorenzi, Luisa
Polverelli, Nicola
Radici, Vera
Morello, Enrico
Colnaghi, Federica
Almici, Camillo
Ferrari, Emilio
Bianchetti, Andrea
Leoni, Alessandro
Re, Federica
Bosio, Katia
Bernardi, Simona
Malagola, Michele
Re, Alessandro
Russo, Domenico
author_sort Accorsi Buttini, Eugenia
collection PubMed
description BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy represents the most advanced immunotherapy against relapsed/refractory B cell malignancies. While cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are distinctive, known CAR T-cell acute adverse events, hematological toxicity has been increasingly reported. Cytopenia following CAR T-cell treatment is attributed in most cases to lymphodepletion regimens, bridging chemotherapy, or radiotherapy. However, when cytopenia becomes prolonged, the development of myelodysplastic syndrome (MDS) should be considered. CASE PRESENTATION: We report a case of high risk (HR)-MDS following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma. Eight months after CAR T-cell infusion, the blood count showed progressive, worsening cytopenia and the bone marrow biopsy revealed multilineage dysplasia without excess of blasts associated with chromosome 7 deletion and RUNX1 mutation. Next generation sequencing analysis, retrospectively performed on stored samples, showed a germ line CSF3R mutation, CEBPA clonal hematopoiesis, but no RUNX1 lesion. CONCLUSION: We describe a case of HR-MDS, with deletion of chromosome 7 and acquisition of RUNX1 mutation, developing after CAR T-cell therapy in a patient with clonal hematopoiesis (CH). Previous chemotherapy favored MDS onset; however, we could not exclude the fact that the impairment of immunosurveillance related to either lymphodepletion or CAR T-cell infusion may play a role in MDS development. Thus, we designed a multicenter prospective study (ClonHema-CAR-T-Study) to investigate if cytopenia after CAR T-cell treatment may be due to underling CH as well as the presence of secondary myeloid malignancies.
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spelling pubmed-98970552023-02-04 High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review Accorsi Buttini, Eugenia Farina, Mirko Lorenzi, Luisa Polverelli, Nicola Radici, Vera Morello, Enrico Colnaghi, Federica Almici, Camillo Ferrari, Emilio Bianchetti, Andrea Leoni, Alessandro Re, Federica Bosio, Katia Bernardi, Simona Malagola, Michele Re, Alessandro Russo, Domenico Front Oncol Oncology BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy represents the most advanced immunotherapy against relapsed/refractory B cell malignancies. While cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are distinctive, known CAR T-cell acute adverse events, hematological toxicity has been increasingly reported. Cytopenia following CAR T-cell treatment is attributed in most cases to lymphodepletion regimens, bridging chemotherapy, or radiotherapy. However, when cytopenia becomes prolonged, the development of myelodysplastic syndrome (MDS) should be considered. CASE PRESENTATION: We report a case of high risk (HR)-MDS following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma. Eight months after CAR T-cell infusion, the blood count showed progressive, worsening cytopenia and the bone marrow biopsy revealed multilineage dysplasia without excess of blasts associated with chromosome 7 deletion and RUNX1 mutation. Next generation sequencing analysis, retrospectively performed on stored samples, showed a germ line CSF3R mutation, CEBPA clonal hematopoiesis, but no RUNX1 lesion. CONCLUSION: We describe a case of HR-MDS, with deletion of chromosome 7 and acquisition of RUNX1 mutation, developing after CAR T-cell therapy in a patient with clonal hematopoiesis (CH). Previous chemotherapy favored MDS onset; however, we could not exclude the fact that the impairment of immunosurveillance related to either lymphodepletion or CAR T-cell infusion may play a role in MDS development. Thus, we designed a multicenter prospective study (ClonHema-CAR-T-Study) to investigate if cytopenia after CAR T-cell treatment may be due to underling CH as well as the presence of secondary myeloid malignancies. Frontiers Media S.A. 2023-01-20 /pmc/articles/PMC9897055/ /pubmed/36741006 http://dx.doi.org/10.3389/fonc.2023.1036455 Text en Copyright © 2023 Accorsi Buttini, Farina, Lorenzi, Polverelli, Radici, Morello, Colnaghi, Almici, Ferrari, Bianchetti, Leoni, Re, Bosio, Bernardi, Malagola, Re and Russo 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
Accorsi Buttini, Eugenia
Farina, Mirko
Lorenzi, Luisa
Polverelli, Nicola
Radici, Vera
Morello, Enrico
Colnaghi, Federica
Almici, Camillo
Ferrari, Emilio
Bianchetti, Andrea
Leoni, Alessandro
Re, Federica
Bosio, Katia
Bernardi, Simona
Malagola, Michele
Re, Alessandro
Russo, Domenico
High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review
title High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review
title_full High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review
title_fullStr High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review
title_full_unstemmed High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review
title_short High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review
title_sort high risk-myelodysplastic syndrome following car t-cell therapy in a patient with relapsed diffuse large b cell lymphoma: a case report and literature review
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897055/
https://www.ncbi.nlm.nih.gov/pubmed/36741006
http://dx.doi.org/10.3389/fonc.2023.1036455
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