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Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy

Background: Chimeric antigen receptor (CAR) T-cells are changing the therapeutic landscape of hematologic malignancies. Severe side effects include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but prolonged cytopenia has also been reported. The...

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Autores principales: Kiem, Dominik, Leisch, Michael, Neureiter, Daniel, Haslauer, Theresa, Egle, Alexander, Melchardt, Thomas, Topp, Max S., Greil, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196726/
https://www.ncbi.nlm.nih.gov/pubmed/34064196
http://dx.doi.org/10.3390/ijms22115449
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author Kiem, Dominik
Leisch, Michael
Neureiter, Daniel
Haslauer, Theresa
Egle, Alexander
Melchardt, Thomas
Topp, Max S.
Greil, Richard
author_facet Kiem, Dominik
Leisch, Michael
Neureiter, Daniel
Haslauer, Theresa
Egle, Alexander
Melchardt, Thomas
Topp, Max S.
Greil, Richard
author_sort Kiem, Dominik
collection PubMed
description Background: Chimeric antigen receptor (CAR) T-cells are changing the therapeutic landscape of hematologic malignancies. Severe side effects include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but prolonged cytopenia has also been reported. The underlying mechanism for prolonged cytopenia is poorly understood so far. Cases: Severe pancytopenia with grade 2-3 anemia was marked 2–3 months after treatment. Laboratory evaluation revealed undetectable levels of haptoglobin with increased reticulocyte counts. Coomb’s tests were negative, no schistocytes were detected on blood smear, and infectious causes were ruled out. Increased erythropoiesis without lymphoma infiltration was noted on bone marrow biopsy. A spontaneous increase in haptoglobin and hemoglobin levels was observed after several weeks. For one patient, peripheral CAR-T levels were monitored over time. We observed a decline at the same time as hemoglobin levels began to rise, implying a potential causality. Conclusion: To our knowledge, we describe the first two cases of Coombs-negative hemolytic anemia after CAR-T treatment for B-cell lymphoma. We encourage routine monitoring for hemolytic anemia after CAR-T treatment and also encourage further investigations on the underlying mechanism.
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spelling pubmed-81967262021-06-13 Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy Kiem, Dominik Leisch, Michael Neureiter, Daniel Haslauer, Theresa Egle, Alexander Melchardt, Thomas Topp, Max S. Greil, Richard Int J Mol Sci Case Report Background: Chimeric antigen receptor (CAR) T-cells are changing the therapeutic landscape of hematologic malignancies. Severe side effects include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but prolonged cytopenia has also been reported. The underlying mechanism for prolonged cytopenia is poorly understood so far. Cases: Severe pancytopenia with grade 2-3 anemia was marked 2–3 months after treatment. Laboratory evaluation revealed undetectable levels of haptoglobin with increased reticulocyte counts. Coomb’s tests were negative, no schistocytes were detected on blood smear, and infectious causes were ruled out. Increased erythropoiesis without lymphoma infiltration was noted on bone marrow biopsy. A spontaneous increase in haptoglobin and hemoglobin levels was observed after several weeks. For one patient, peripheral CAR-T levels were monitored over time. We observed a decline at the same time as hemoglobin levels began to rise, implying a potential causality. Conclusion: To our knowledge, we describe the first two cases of Coombs-negative hemolytic anemia after CAR-T treatment for B-cell lymphoma. We encourage routine monitoring for hemolytic anemia after CAR-T treatment and also encourage further investigations on the underlying mechanism. MDPI 2021-05-21 /pmc/articles/PMC8196726/ /pubmed/34064196 http://dx.doi.org/10.3390/ijms22115449 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Kiem, Dominik
Leisch, Michael
Neureiter, Daniel
Haslauer, Theresa
Egle, Alexander
Melchardt, Thomas
Topp, Max S.
Greil, Richard
Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy
title Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy
title_full Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy
title_fullStr Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy
title_full_unstemmed Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy
title_short Two Cases of Pancytopenia with Coombs-Negative Hemolytic Anemia after Chimeric Antigen Receptor T-Cell Therapy
title_sort two cases of pancytopenia with coombs-negative hemolytic anemia after chimeric antigen receptor t-cell therapy
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196726/
https://www.ncbi.nlm.nih.gov/pubmed/34064196
http://dx.doi.org/10.3390/ijms22115449
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