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Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study

BACKGROUND: Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients...

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Autores principales: Zhao, Houli, Wei, Jieping, Wei, Guoqing, Luo, Yi, Shi, Jimin, Cui, Qu, Zhao, Mingfeng, Liang, Aibin, Zhang, Qing, Yang, Jianmin, Li, Xin, Chen, Jing, Song, Xianmin, Jing, Hongmei, Li, Yuhua, Hao, Siguo, Wu, Wenjun, Tan, Yamin, Yu, Jian, Zhao, Yanmin, Lai, Xiaoyu, Yin, Elaine Tan Su, Wei, Yunxiong, Li, Ping, Huang, Jing, Wang, Tao, Blaise, Didier, Xiao, Lei, Chang, Alex H., Nagler, Arnon, Mohty, Mohamad, Huang, He, Hu, Yongxian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199358/
https://www.ncbi.nlm.nih.gov/pubmed/32366260
http://dx.doi.org/10.1186/s13045-020-00873-7
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author Zhao, Houli
Wei, Jieping
Wei, Guoqing
Luo, Yi
Shi, Jimin
Cui, Qu
Zhao, Mingfeng
Liang, Aibin
Zhang, Qing
Yang, Jianmin
Li, Xin
Chen, Jing
Song, Xianmin
Jing, Hongmei
Li, Yuhua
Hao, Siguo
Wu, Wenjun
Tan, Yamin
Yu, Jian
Zhao, Yanmin
Lai, Xiaoyu
Yin, Elaine Tan Su
Wei, Yunxiong
Li, Ping
Huang, Jing
Wang, Tao
Blaise, Didier
Xiao, Lei
Chang, Alex H.
Nagler, Arnon
Mohty, Mohamad
Huang, He
Hu, Yongxian
author_facet Zhao, Houli
Wei, Jieping
Wei, Guoqing
Luo, Yi
Shi, Jimin
Cui, Qu
Zhao, Mingfeng
Liang, Aibin
Zhang, Qing
Yang, Jianmin
Li, Xin
Chen, Jing
Song, Xianmin
Jing, Hongmei
Li, Yuhua
Hao, Siguo
Wu, Wenjun
Tan, Yamin
Yu, Jian
Zhao, Yanmin
Lai, Xiaoyu
Yin, Elaine Tan Su
Wei, Yunxiong
Li, Ping
Huang, Jing
Wang, Tao
Blaise, Didier
Xiao, Lei
Chang, Alex H.
Nagler, Arnon
Mohty, Mohamad
Huang, He
Hu, Yongxian
author_sort Zhao, Houli
collection PubMed
description BACKGROUND: Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from haploidentical hematopoietic stem cell transplantation after CAR-T therapy. METHODS: A total of 122 patients after CAR-T therapy were enrolled, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haploidentical hematopoietic stem cell transplantation (transplant group). Long-term outcome was assessed, as was its association with baseline patient characteristics. RESULTS: Compared with the non-transplant group, transplantation recipients had a higher 2-year overall survival (OS; 77.0% versus 36.4%; P < 0.001) and leukemia-free survival (LFS; 65.6% versus 32.8%; P < 0.001). Multivariate analysis showed that minimal residual disease (MRD) positivity at transplantation is an independent factor associated with poor LFS (P = 0.005), OS (P = 0.035), and high cumulative incidence rate of relapse (P = 0.045). Pre-transplant MRD-negative recipients (MRD− group) had a lower cumulative incidence of relapse (17.3%) than those in the non-transplant group (67.2%; P < 0.001) and pre-transplant MRD-positive recipients (MRD+ group) (65.8%; P = 0.006). The cumulative incidence of relapse in MRD+ and non-transplant groups did not differ significantly (P = 0.139). The 2-year LFS in the non-transplant, MRD+, and MRD− groups was 32.8%, 27.6%, and 76.1%, respectively. The MRD− group had a higher LFS than the non-transplantation group (P < 0.001) and MRD+ group (P = 0.007), whereas the LFS in the MRD+ and non-transplant groups did not differ significantly (P = 0.305). The 2-year OS of the MRD− group was higher than that of the non-transplant group (83.3% versus 36.4%; P < 0.001) but did not differ from that of the MRD+ group (83.3% versus 62.7%; P = 0.069). The OS in the non-transplant and MRD+ groups did not differ significantly (P = 0.231). CONCLUSION: Haploidentical hematopoietic stem cell transplantation with pre-transplant MRD negativity after CAR-T therapy could greatly improve LFS and OS in patients with relapsed/refractory acute lymphoblastic leukemia. TRIAL REGISTRATION: The study was registered in the Chinese clinical trial registry (ChiCTR1900023957).
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spelling pubmed-71993582020-05-08 Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study Zhao, Houli Wei, Jieping Wei, Guoqing Luo, Yi Shi, Jimin Cui, Qu Zhao, Mingfeng Liang, Aibin Zhang, Qing Yang, Jianmin Li, Xin Chen, Jing Song, Xianmin Jing, Hongmei Li, Yuhua Hao, Siguo Wu, Wenjun Tan, Yamin Yu, Jian Zhao, Yanmin Lai, Xiaoyu Yin, Elaine Tan Su Wei, Yunxiong Li, Ping Huang, Jing Wang, Tao Blaise, Didier Xiao, Lei Chang, Alex H. Nagler, Arnon Mohty, Mohamad Huang, He Hu, Yongxian J Hematol Oncol Rapid Communication BACKGROUND: Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from haploidentical hematopoietic stem cell transplantation after CAR-T therapy. METHODS: A total of 122 patients after CAR-T therapy were enrolled, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haploidentical hematopoietic stem cell transplantation (transplant group). Long-term outcome was assessed, as was its association with baseline patient characteristics. RESULTS: Compared with the non-transplant group, transplantation recipients had a higher 2-year overall survival (OS; 77.0% versus 36.4%; P < 0.001) and leukemia-free survival (LFS; 65.6% versus 32.8%; P < 0.001). Multivariate analysis showed that minimal residual disease (MRD) positivity at transplantation is an independent factor associated with poor LFS (P = 0.005), OS (P = 0.035), and high cumulative incidence rate of relapse (P = 0.045). Pre-transplant MRD-negative recipients (MRD− group) had a lower cumulative incidence of relapse (17.3%) than those in the non-transplant group (67.2%; P < 0.001) and pre-transplant MRD-positive recipients (MRD+ group) (65.8%; P = 0.006). The cumulative incidence of relapse in MRD+ and non-transplant groups did not differ significantly (P = 0.139). The 2-year LFS in the non-transplant, MRD+, and MRD− groups was 32.8%, 27.6%, and 76.1%, respectively. The MRD− group had a higher LFS than the non-transplantation group (P < 0.001) and MRD+ group (P = 0.007), whereas the LFS in the MRD+ and non-transplant groups did not differ significantly (P = 0.305). The 2-year OS of the MRD− group was higher than that of the non-transplant group (83.3% versus 36.4%; P < 0.001) but did not differ from that of the MRD+ group (83.3% versus 62.7%; P = 0.069). The OS in the non-transplant and MRD+ groups did not differ significantly (P = 0.231). CONCLUSION: Haploidentical hematopoietic stem cell transplantation with pre-transplant MRD negativity after CAR-T therapy could greatly improve LFS and OS in patients with relapsed/refractory acute lymphoblastic leukemia. TRIAL REGISTRATION: The study was registered in the Chinese clinical trial registry (ChiCTR1900023957). BioMed Central 2020-05-04 /pmc/articles/PMC7199358/ /pubmed/32366260 http://dx.doi.org/10.1186/s13045-020-00873-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Rapid Communication
Zhao, Houli
Wei, Jieping
Wei, Guoqing
Luo, Yi
Shi, Jimin
Cui, Qu
Zhao, Mingfeng
Liang, Aibin
Zhang, Qing
Yang, Jianmin
Li, Xin
Chen, Jing
Song, Xianmin
Jing, Hongmei
Li, Yuhua
Hao, Siguo
Wu, Wenjun
Tan, Yamin
Yu, Jian
Zhao, Yanmin
Lai, Xiaoyu
Yin, Elaine Tan Su
Wei, Yunxiong
Li, Ping
Huang, Jing
Wang, Tao
Blaise, Didier
Xiao, Lei
Chang, Alex H.
Nagler, Arnon
Mohty, Mohamad
Huang, He
Hu, Yongxian
Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
title Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
title_full Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
title_fullStr Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
title_full_unstemmed Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
title_short Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
title_sort pre-transplant mrd negativity predicts favorable outcomes of car-t therapy followed by haploidentical hsct for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
topic Rapid Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199358/
https://www.ncbi.nlm.nih.gov/pubmed/32366260
http://dx.doi.org/10.1186/s13045-020-00873-7
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