Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation

Chen, Yuhong; Zhang, Xian; Cheng, Yifei; Chen, Huan; Mo, Xiao‐Dong; Yan, Chen‐Hua; Chen, Yao; Wang, Han; Sun, Yu‐Qian; Wang, Yu; Zhang, Xiao-Hui; Xu, Lei; Liu, Kai-Yan; Yang, Junfang; Zhang, Jianping; Zhang, Gailing; Shi, Yanze; Su, Yunchao; Li, Wenqian; Song, Dan; Zhang, Min; Lu, Peihua; Huang, Xiao‐Jun

doi:10.1016/j.jcyt.2020.08.002

Cited by 33 publications

(34 citation statements)

References 24 publications

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“…Huang XJ et al reported that out of 34 evaluable patients, 7 patients developed GVHD, with mild chronic GVHD in 1 case and aGVHD in 6 cases (2 grade II aGVHD, 3 grade III aGVHD and 1 grade IV aGVHD). The occurrence of GVHD had a poor effect on survival (24). A study by Zhang X et al showed that 2 out of 43 patients with posttransplant relapse developed ≤ grade II aGVHD when receiving allogeneic CD19 CAR T cells (25).…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

et al. 2021

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Twenty patients with relapsed B-ALL after HSCT were treated with CAR T cell therapy and were evaluated for efficacy and safety. Twelve patients previously received haploidentical transplantation, while 8 patients received HLA-matched transplantation. The median relapse time was 12 months (range, 4 to 72). Thirteen patients received autologous CAR T cells, and 7 patients received allogeneic CAR T cells, which were derived from transplant donors. The median infusion dose was 2.9×106/kg (range, 0.33 to 12×106/kg). Nineteen patients were evaluated for efficacy, among which 17 patients (89.5%) achieved MRD negative. The CR rates in the HLA-matched transplantation group and haploidentical transplantation group were 100% (7/7) and 83.3% (10/12), respectively. The median follow-up time was 9.80 months (range, 2.40 to 64.97). Ten patients (50%) died of relapse, 3 patients (15%) died of infection, and 1 patient (5%) died of aGVHD. Fifteen patients (75%) developed CRS, including 3 (20%) grade 1 CRS, 6 (40%) grade 2 CRS, and 6 (40%) grade 3 CRS. Ten patients (50%) developed aGVHD, including 1 (10%) grade I aGVHD, 6 (60%) grade II aGVHD, and 3 (30%) grade III aGVHD. The log rank test showed that CAR T cell origin was correlated with aGVHD occurrence in the haploidentical transplantation group (P = 0.005). The authors’ study indicated that the initial efficacy and safety of CAR T cell therapy for patients with post-transplant relapse were satisfactory. However, aGVHD was a concern in patients with a history of haploidentical transplantation occupied with allogeneic CAR T cells, which warrants clinical attention.

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Section: Discussionmentioning

confidence: 99%

“…reported that out of 34 evaluable patients, 7 patients developed GVHD, with mild chronic GVHD in 1 case and aGVHD in 6 cases (2 grade II aGVHD, 3 grade III aGVHD and 1 grade IV aGVHD). The occurrence of GVHD had a poor effect on survival ( 24 ). A study by Zhang X et al.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

et al. 2021

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“…Moreover, preliminary results from several clinical trials show that donor CAR-T cells exert potent GVL activity in the absence of damaging GVHD activity (28)(29)(30). Donor-derived CAR-T cells and recipient-derived CAR-T cells seem to have similar efficacy and safety, probably owing to the same original allogenic donor immune system, although larger clinical studies are needed (31,32). Considering insufficient T lymphocytes postchemotherapy and possible T cell dysfunction owing to the immunosuppressive agent used to control GVHD, donor T cells were collected for CAR-T cell preparation.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Successful Chimeric Antigen Receptor T Cell Therapy in Haploidentical-Allogeneic Stem Cell Transplant Patients With Post-Transplant Lymphoproliferative Disorder

Yan¹,

Wang²,

Zhang³

et al. 2021

Front. Oncol.

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BackgroundEpstein–Barr virus-associated post-transplant lymphoproliferative disorder (EBV-PTLD) is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Rituximab has been proven to dramatically improve the prognosis of patients with EBV reactivation and PTLD. However, reports on the curative management of refractory PTLD are scarce.Case PresentationIn this report, we describe the successful management of two patients with EBV-PTLD with chimeric antigen receptor T-cell (CAR-T) therapy.ConclusionThe present results demonstrated that patients with EBV-PTLD may benefit from CAR-T therapy and that the toxicity is manageable. Further studies are needed to verify these findings.

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“…Although a high MRD-negative CR rate was achieved after CAR-T therapy, the long-term efficacy was unsatisfactory due to loss of the CAR-T cells resulting from the limited long-term persistence, the immune-suppressive microenvironment, and exhaustion of CAR-T cells (11,12). It is necessary to optimize the strategy of treatment to further improve long-term efficacy after CAR-T cell infusion.…”

Section: Introductionmentioning

confidence: 99%

Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy

Chen

Shen

et al. 2021

Front. Immunol.

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Early response could be obtained in most patients with relapsed or refractory B cell lymphoblastic leukemia (R/R B-ALL) treated with chimeric antigen receptor T-cell (CAR-T) therapy, but relapse occurs in some patients. There is no consensus on treatment strategy post CAR-T cell therapy. In this retrospective study of humanized CD19-targeted CAR-T cell (hCART19s) therapy for R/R B-ALL, we analyzed the patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or received a second hCART19s infusion, and summarized their efficacy and safety. We retrospectively studied 28 R/R B-ALL patients treated with hCART19s in the Affiliated Hospital of Xuzhou Medical University from 2016 to 2020. After the first hCART19s infusion, 10 patients received allo-HSCT (CART+HSCT group), 7 patients received a second hCART19s infusion (CART2 group), and 11 patients did not receive HSCT or a second hCART19s infusion (CART1 group). The safety, efficacy, and long-term survival were analyzed. Of the 28 patients who received hCART19s treatment, 1 patient could not be evaluated for efficacy, and 25 (92.6%) achieved complete remission (CR) with 20 (74.7%) achieving minimal residual disease (MRD) negativity. Seven (25%) patients experienced grade 3-4 CRS, and one died from grade 5 CRS. No patient experienced ≥3 grade ICANS. The incidence of second CR is higher in the CART+HSCT group compared to the CART2 group (100% vs. 42.9%, p=0.015). The median follow-up time was 1,240 days (range: 709–1,770). Significantly longer overall survival (OS) and leukemia-free survival (LFS) were achieved in the CART+HSCT group (median OS and LFS: not reached, p=0.006 and 0.001, respectively) compared to the CART2 group (median OS: 482; median LFS: 189) and the CART1 group (median OS: 236; median LFS: 35). In the CART+HSCT group, the incidence of acute graft-versus-host disease (aGVHD) was 30% (3/10), and transplantation-related mortality was 30% (3/10). No chronic GVHD occurred. Multivariate analysis results showed that blasts ≥ 20% in the bone marrow and MRD ≥ 65.6% are independent factors for inferior OS and LFS, respectively, while receiving allo-HSCT is an independent factor associated with both longer OS and LFS. In conclusion, early allo-HSCT after CAR-T therapy can achieve long-term efficacy, and the adverse events are controllable.

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Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation

Cited by 33 publications

References 24 publications

Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

Efficacy and Safety of Chimeric Antigen Receptor T Cells in Acute Lymphoblastic Leukemia With Post-Transplant Relapse

Case Report: Successful Chimeric Antigen Receptor T Cell Therapy in Haploidentical-Allogeneic Stem Cell Transplant Patients With Post-Transplant Lymphoproliferative Disorder

Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy

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