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, Yiping; Li, Ping; Huang, Jing; Wang, Tao; Blaise, Didier; Xiao, Lanbo; Chang, Alex H.; Nagler, Arnon; Mohty, Mohamad; Huang, He; Hu, Yongxian

doi:10.1186/s13045-020-00873-7

Cited by 62 publications

(62 citation statements)

References 41 publications

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“…Park et al ( 9 ) reported that 17 of 53 patients received allo-HSCT after 19–28z CAR T-cell therapy, and their OS or LFS was not significantly different from those who did not undergo HSCT. In contrast, there is accumulating evidence supporting the benefit of consolidative HSCT ( 186 – 188 ). A multicenter retrospective study indicated that haploidentical HSCT after CD19 CAR T-cell therapy could benefit patients, with great improvement in LFS and OS compared with the nontransplant group (65.6% versus 32.8% P < 0.001; 77.0% versus 36.4%, P < 0.001) and no increased risk of treatment-related toxicity compared with previous values.…”

Section: Clinical Strategiesmentioning

confidence: 99%

“…A multicenter retrospective study indicated that haploidentical HSCT after CD19 CAR T-cell therapy could benefit patients, with great improvement in LFS and OS compared with the nontransplant group (65.6% versus 32.8% P < 0.001; 77.0% versus 36.4%, P < 0.001) and no increased risk of treatment-related toxicity compared with previous values. It also identified pretransplant MRD negativity as an important independent predictor of high LFS and OS ( 186 ). Gu et al ( 187 ) reported similar conclusions after analyzing 56 adults with R/R Ph+ ALL who received allo-HSCT post-CD19 CAR T-cell therapy.…”

Section: Clinical Strategiesmentioning

confidence: 99%

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Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Huang

Xiao

et al. 2021

Front. Immunol.

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Chimeric antigen receptor (CAR) T-cell therapy exhibits desirable and robust efficacy in patients with acute lymphoblastic leukemia (ALL). Stimulated by the revolutionized progress in the use of FDA-approved CD19 CAR T cells, novel agents with CAR designs and targets are being produced in pursuit of superior performance. However, on the path from bench to bedside, new challenges emerge. Accessibility is considered the initial barrier to the transformation of this patient-specific product into a commercially available product. To ensure infusion safety, profound comprehension of adverse events and proactive intervention are required. Additionally, resistance and relapse are the most critical and intractable issues in CAR T-cell therapy for ALL, thus precluding its further development. Understanding the limitations through up-to-date insights and characterizing multiple strategies will be critical to leverage CAR T-cell therapy flexibly for use in clinical situations. Herein, we provide an overview of the application of CAR T-cell therapy in ALL, emphasizing the main challenges and potential clinical strategies in an effort to promote a standardized set of treatment paradigms for ALL.

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Section: Clinical Strategiesmentioning

confidence: 99%

Section: Clinical Strategiesmentioning

confidence: 99%

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Huang

Xiao

et al. 2021

Front. Immunol.

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“…A long-term follow-up study indicated that late consolidative allo-HSCT (more than 80 days after CAR T-cell infusion) significantly increased the risk of death [33]. A recent published retrospective study indicated a lower incidence of relapse and a higher 2-year LFS in pre-transplant MRD-negative patients than in pre-transplant MRD-positive patients [53]. Besides, the relapse rate of MRD-negative CR patients was approximately 10% three months after CAR T-cell therapy [1,21,28].…”

Section: Therapeutic Window and Consolidative Allo-hsct Regimenmentioning

confidence: 99%

Consolidative allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: who? When? Why?

Jiang

Mei

2020

Biomark Res

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Although anti-CD19 chimeric antigen receptor (CAR) T-cell therapy shows good efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), it fails to improve long-term leukemia-free survival (LFS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR T-cell therapy has emerged as a promising strategy to prolong LFS. Nevertheless, which patients are likely to benefit from consolidative allo-HSCT, as well as the optimal therapeutic window, remain to be explored. Recent clinical data indicate that patients with complex karyotypes, adverse genes, and high pre-infusion minimal residual disease (MRD) by flow cytometry in the bone marrow, were at high risk of relapse after CAR T-cell therapy. High pre-lymphodepletion lactate dehydrogenase, low pre-lymphodepletion platelet count, absence of fludarabine in lymphodepletion, persistent leukemic sequence by high throughput sequencing in bone marrow after CAR T-cell infusion, and early loss of CAR T cells have also been linked to relapse after CAR T-cell therapy. In patients having these risk factors, consolidative allo-HSCT after CAR T-cell therapy may prolong LFS. Allo-HSCT provides optimal clinical benefit in patients with MRD-negative complete remission, typically within three months after CAR T-cell therapy. Herein, we summarize the clinical data on consolidative allo-HSCT after anti-CD19 CAR T-cell therapy, as well as the potential factors associated with allo-HSCT benefit. We also discuss the optimal therapeutic window and regimen of consolidative allo-HSCT. Finally, and most importantly, we provide recommendations for the assessment and management of r/r B-ALL patients undergoing anti-CD19 CAR T-cell therapy.

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“…gov Identifier: NCT03533816, NCT03862833) about using γδ T cells for transplantation improvement are ongoing, but the results of these clinical studies have not been reported. Now HSCT following chimeric antigen receptor (CAR)-T therapy were reported favorable outcomes like higher OS and lower relapsed rate 98 , 99 . CAR-γδ T cells therapy was a novel promote immunotherapy for antitumor 100 and CAR-γδ T cells may be a potential immunological treatment to improve clinical outcomes of HSCT.…”

Section: γδ T Cells and Immunotherapymentioning

confidence: 99%

The Roles of γδ T Cells in Hematopoietic Stem Cell Transplantation

Kong

Zhang

et al. 2020

Cell Transplant

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The αβ T-cell-depleted hematopoietic stem cell transplantation (HSCT) leads to lower relapse and better outcome, and may correlate strongly with expansion of donor-derived γδ T cells. γδ T cells play an important role in immune reconstitution and can exert a graft-versus-leukemia effect after HSCT. This review showed the recent literature on immune functions of γδ T cells after HSCT. The discrepancies between studies of γδ T cells in graft-versus-host disease may cause by its heterogeneous and various distinct subsets. And reconstitution of γδ T cells may play a potential immunoregulatory role in the infections after HSCT.

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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

Cited by 62 publications

References 41 publications

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments

Consolidative allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor T-cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia: who? When? Why?

The Roles of γδ T Cells in Hematopoietic Stem Cell Transplantation

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