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Severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor T cell therapy for refractory acute lymphoblastic leukemia
Cytokine release syndrome (CRS), which may be associated with fever, hypotension, hypoxia, and organ damage, is caused by a massive cytokine release after chimeric antigen receptor (CAR)-T cell therapy. We present the case of a patient who developed severe bloody diarrhea due to CRS after CAR-T cell...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Asia-Pacific Blood and Marrow Transplantation Group
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847265/ https://www.ncbi.nlm.nih.gov/pubmed/36714263 http://dx.doi.org/10.31547/bct-2021-009 |
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author | Shima, Haruko Ishikawa, Takahiro Ito, Jumpei Emoto, Katsura Kurosawa, Takumi Keino, Dai Yamazaki, Fumito Goto, Hiroaki Shimada, Hiroyuki |
author_facet | Shima, Haruko Ishikawa, Takahiro Ito, Jumpei Emoto, Katsura Kurosawa, Takumi Keino, Dai Yamazaki, Fumito Goto, Hiroaki Shimada, Hiroyuki |
author_sort | Shima, Haruko |
collection | PubMed |
description | Cytokine release syndrome (CRS), which may be associated with fever, hypotension, hypoxia, and organ damage, is caused by a massive cytokine release after chimeric antigen receptor (CAR)-T cell therapy. We present the case of a patient who developed severe bloody diarrhea due to CRS after CAR-T cell infusion. A 10-year-old boy presented with a second relapse of B-cell precursor acute lymphoblastic leukemia 6 months after hematopoietic stem cell transplantation from an unrelated donor. CAR-T cells (tisagenlecleucel) were infused at the third complete remission after salvage chemotherapy. While fever >39°C was sustained from day 4, circulatory and respiratory status remained stable. However, he experienced severe bloody diarrhea. There was no evidence of infection; lower gastrointestinal (GI) endoscopy revealed extensive edema with erosion and ulceration, suggestive of non-specific intestinal inflammation. Thus, we considered CRS-associated grade 3 GI damage and administered a single dose of tocilizumab for grade 2 CRS, followed by 4 days of corticosteroids. Afterwards, no fever or GI bleeding was observed. Biopsy of the intestinal mucosa revealed ulcerative change with a lack of epithelial cells, which may correspond to histologic grade 4 graft versus host disease (GVHD). However, diarrhea corresponded to stage 1 GVHD, and the GVHD risk after CAR-T cell infusion has been reported to be rare in clinical practice. Although severe GI symptoms associated with CRS after CAR-T therapy are rare, early tocilizumab use is recommended for non-infectious severe GI symptoms to avoid long-term corticosteroid use, which may reduce CAR-T cell efficacy. |
format | Online Article Text |
id | pubmed-9847265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Asia-Pacific Blood and Marrow Transplantation Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-98472652023-01-27 Severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor T cell therapy for refractory acute lymphoblastic leukemia Shima, Haruko Ishikawa, Takahiro Ito, Jumpei Emoto, Katsura Kurosawa, Takumi Keino, Dai Yamazaki, Fumito Goto, Hiroaki Shimada, Hiroyuki Blood Cell Ther Case Report Cytokine release syndrome (CRS), which may be associated with fever, hypotension, hypoxia, and organ damage, is caused by a massive cytokine release after chimeric antigen receptor (CAR)-T cell therapy. We present the case of a patient who developed severe bloody diarrhea due to CRS after CAR-T cell infusion. A 10-year-old boy presented with a second relapse of B-cell precursor acute lymphoblastic leukemia 6 months after hematopoietic stem cell transplantation from an unrelated donor. CAR-T cells (tisagenlecleucel) were infused at the third complete remission after salvage chemotherapy. While fever >39°C was sustained from day 4, circulatory and respiratory status remained stable. However, he experienced severe bloody diarrhea. There was no evidence of infection; lower gastrointestinal (GI) endoscopy revealed extensive edema with erosion and ulceration, suggestive of non-specific intestinal inflammation. Thus, we considered CRS-associated grade 3 GI damage and administered a single dose of tocilizumab for grade 2 CRS, followed by 4 days of corticosteroids. Afterwards, no fever or GI bleeding was observed. Biopsy of the intestinal mucosa revealed ulcerative change with a lack of epithelial cells, which may correspond to histologic grade 4 graft versus host disease (GVHD). However, diarrhea corresponded to stage 1 GVHD, and the GVHD risk after CAR-T cell infusion has been reported to be rare in clinical practice. Although severe GI symptoms associated with CRS after CAR-T therapy are rare, early tocilizumab use is recommended for non-infectious severe GI symptoms to avoid long-term corticosteroid use, which may reduce CAR-T cell efficacy. Asia-Pacific Blood and Marrow Transplantation Group 2021-01-28 /pmc/articles/PMC9847265/ /pubmed/36714263 http://dx.doi.org/10.31547/bct-2021-009 Text en Copyright Ⓒ2022 Asia-Pacific Blood and Marrow Transplantation Group (APBMT). https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under CC BY-NC license (https://creativecommons.org/licenses/by-nc/4.0/). |
spellingShingle | Case Report Shima, Haruko Ishikawa, Takahiro Ito, Jumpei Emoto, Katsura Kurosawa, Takumi Keino, Dai Yamazaki, Fumito Goto, Hiroaki Shimada, Hiroyuki Severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor T cell therapy for refractory acute lymphoblastic leukemia |
title | Severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor T cell therapy for refractory acute lymphoblastic leukemia |
title_full | Severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor T cell therapy for refractory acute lymphoblastic leukemia |
title_fullStr | Severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor T cell therapy for refractory acute lymphoblastic leukemia |
title_full_unstemmed | Severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor T cell therapy for refractory acute lymphoblastic leukemia |
title_short | Severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor T cell therapy for refractory acute lymphoblastic leukemia |
title_sort | severe bloody diarrhea due to cytokine release syndrome after chimeric antigen receptor t cell therapy for refractory acute lymphoblastic leukemia |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9847265/ https://www.ncbi.nlm.nih.gov/pubmed/36714263 http://dx.doi.org/10.31547/bct-2021-009 |
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