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Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia
Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO–positive acute myeloid cell transplantation. Methods: A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO–positive AML post transplantation but negative flow...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880285/ https://www.ncbi.nlm.nih.gov/pubmed/36712661 http://dx.doi.org/10.3389/fphar.2022.1059930 |
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author | Xi, Yang Chenglong, Li Rong, Zhang Wen, Wang Yu, Wang Jiao, Chen Juan, Huang Feifei, Che Rong, Xiao Tao, Jiang Hui, Li Xiaobing, Huang |
author_facet | Xi, Yang Chenglong, Li Rong, Zhang Wen, Wang Yu, Wang Jiao, Chen Juan, Huang Feifei, Che Rong, Xiao Tao, Jiang Hui, Li Xiaobing, Huang |
author_sort | Xi, Yang |
collection | PubMed |
description | Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO–positive acute myeloid cell transplantation. Methods: A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO–positive AML post transplantation but negative flow cytometry results. A retrospective analysis was performed of the survival rate and possible influencing factors of patients with relapse treated with this regimen in our center from January 2018 to January 2022. Results: The overall response rate was 95.8% (23/24), and the median number of treatment courses was 4 (range, 3–12 courses). The total molecular complete response (MCR) was 79.1% (19/24) after all treatments, and the molecular complete response was 37.5% (9/24) after one cycle of treatment but reached 58.3% (14/24) after four cycles; overall, the proportion of MCR increased gradually with the increase in treatment cycles. The projected 5-year overall survival rate was 73.9%. The projected 5-year leukemia-free survival rate was 64.8%, and the projected 1-year cumulative relapse rate was 35.5%. The incidence of grade II–IV graft-versus-host diseases (GVHD) was 29.2% (7/24), and that of grade III–IV GVHD was 20.8% (5/24), which could be effectively controlled by glucocorticoid therapy combined with calcineurin inhibitors The total incidence of chronic GVHD was 29.2% (7/24), and all cases were localized chronic GVHD. The total infection rate was 33.3% (8/24), mainly involving bacterial and fungal infections, and the incidence of life-threatening infections was 4.17% (1/24). The treatment-related mortality rate was 0%; and the total mortality rate was 20.8% (5/24). Nausea and vomiting, thrombocytopenia, and neutropenia were common adverse reactions, all of which were Common Terminology Criteria for Adverse Events grade 2–3 events and reversible after drug withdrawal. In terms of immunity, Th1 cell counts gradually increased, Th17 cell counts gradually decreased, and the Th1/Th17 ratio gradually increased after treatment. The CD8(+) T lymphocyte count increased gradually, while the CD4(+) T lymphocyte count did not change significantly. Conclusion: Our chidamide-based 3-drug combination regimen led to a high remission rate and tolerable adverse reactions in patients with AML1-ETO–positive post-transplant relapse, and most patients can achieve long-term survival with this regimen. |
format | Online Article Text |
id | pubmed-9880285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98802852023-01-28 Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia Xi, Yang Chenglong, Li Rong, Zhang Wen, Wang Yu, Wang Jiao, Chen Juan, Huang Feifei, Che Rong, Xiao Tao, Jiang Hui, Li Xiaobing, Huang Front Pharmacol Pharmacology Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO–positive acute myeloid cell transplantation. Methods: A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO–positive AML post transplantation but negative flow cytometry results. A retrospective analysis was performed of the survival rate and possible influencing factors of patients with relapse treated with this regimen in our center from January 2018 to January 2022. Results: The overall response rate was 95.8% (23/24), and the median number of treatment courses was 4 (range, 3–12 courses). The total molecular complete response (MCR) was 79.1% (19/24) after all treatments, and the molecular complete response was 37.5% (9/24) after one cycle of treatment but reached 58.3% (14/24) after four cycles; overall, the proportion of MCR increased gradually with the increase in treatment cycles. The projected 5-year overall survival rate was 73.9%. The projected 5-year leukemia-free survival rate was 64.8%, and the projected 1-year cumulative relapse rate was 35.5%. The incidence of grade II–IV graft-versus-host diseases (GVHD) was 29.2% (7/24), and that of grade III–IV GVHD was 20.8% (5/24), which could be effectively controlled by glucocorticoid therapy combined with calcineurin inhibitors The total incidence of chronic GVHD was 29.2% (7/24), and all cases were localized chronic GVHD. The total infection rate was 33.3% (8/24), mainly involving bacterial and fungal infections, and the incidence of life-threatening infections was 4.17% (1/24). The treatment-related mortality rate was 0%; and the total mortality rate was 20.8% (5/24). Nausea and vomiting, thrombocytopenia, and neutropenia were common adverse reactions, all of which were Common Terminology Criteria for Adverse Events grade 2–3 events and reversible after drug withdrawal. In terms of immunity, Th1 cell counts gradually increased, Th17 cell counts gradually decreased, and the Th1/Th17 ratio gradually increased after treatment. The CD8(+) T lymphocyte count increased gradually, while the CD4(+) T lymphocyte count did not change significantly. Conclusion: Our chidamide-based 3-drug combination regimen led to a high remission rate and tolerable adverse reactions in patients with AML1-ETO–positive post-transplant relapse, and most patients can achieve long-term survival with this regimen. Frontiers Media S.A. 2023-01-13 /pmc/articles/PMC9880285/ /pubmed/36712661 http://dx.doi.org/10.3389/fphar.2022.1059930 Text en Copyright © 2023 Xi, Chenglong, Rong, Wen, Yu, Jiao, Juan, Feifei, Rong, Tao, Hui and Xiaobing. 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 | Pharmacology Xi, Yang Chenglong, Li Rong, Zhang Wen, Wang Yu, Wang Jiao, Chen Juan, Huang Feifei, Che Rong, Xiao Tao, Jiang Hui, Li Xiaobing, Huang Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia |
title | Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia |
title_full | Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia |
title_fullStr | Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia |
title_full_unstemmed | Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia |
title_short | Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia |
title_sort | chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in aml1-eto–positive acute myeloid leukemia |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880285/ https://www.ncbi.nlm.nih.gov/pubmed/36712661 http://dx.doi.org/10.3389/fphar.2022.1059930 |
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