Early and late hematologic toxicity following CD19 CAR-T cells

Fried, Shalev; Avigdor, Abraham; Bielorai, Bella; Meir, Amilia; Besser, Michal J.; Schachter, Jacob; Shimoni, Avichai; Nagler, Arnon; Toren, Amos; Jacoby, Elad

doi:10.1038/s41409-019-0487-3

Cited by 317 publications

(369 citation statements)

References 29 publications

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“…We found that severe myelosuppression already existed when he received infusion of CAR-T cells (Fig. 1c), this is consistent with the report [10]. Applications of the component transfusion and stimulating factor did not improve the myelosuppression, ultimately, it was successfully recovered by autologous stem cell infusion.…”

supporting

confidence: 89%

“…Cohen reported 11 relapsed and refractory MM patients received BCMA targeted CAR-T cells, anemia, neutropenia, lymphopenia, thrombocytopenia, hypofibrinogenemia occurred in each patient [9]. Fried analyzed the persistent severe hematologic toxicity after CD19 CAR-T cells therapy for patients with relapsed and refractory leukemia and lymphoma [10], it was indicated severe myelosuppression was more common in patients with high grade CRS and in patients receiving stem cell transplantation prior to CAR-T therapy. The patient underwent ASCT within 1 year before receiving the CAR-T cell infusion, insufficient recovery of bone marrow hematopoiesis due to intensive chemotherapy, which in turn may result in bone marrow dysfunction under hematopoietic stress.…”

mentioning

confidence: 99%

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Autologous hematopoietic stem cell infusion for sustained myelosuppression after BCMA–CAR-T therapy in patient with relapsed myeloma

Lin

Liu

Han

et al. 2019

Bone Marrow Transplant

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To the Editor, Chimeric antigen receptor (CAR) T-cell targeted multiple myeloma antigens such as CD138, kappa-light chain, and Bcell maturation antigen (BCMA) as well as CD19 had been widely adopted. More and more CART clinical trials for MM presented encouraging results [1-3]. However, current CART treatment still faces the adverse reactions as cytokine release syndrome (CRS), myelosuppression, and other complications, especially, severe myelosuppression is often a fatal threat to patients. We adopted the stem cell infusion to promote hematopoietic recovery for a relapsed MM patient developing severe and persistent myelosuppression after CART cell therapy. A male patient with 56 years old was diagnosed with multiple myeloma, IgG, lambda type, stage II for ISS stage, and III for RISS stage. He had received nine courses of treatment including one course of PD regimen (bortezomib combined with dexamethasone) and eight courses of PAD regimen (bortezomib, epirubicin, and dexamethasone) before auto-stem cell transplantation (ASCT) and achieved the complete remission according to the evaluation criteria of the IMWG. Sufficient number of hematopoietic stem cells (6.2 × 10 8 /kg for MNC and 5.6 × 10 8 /kg for CD34 + cells) were harvested. On November 23, 2017, the patient received highdose melphalan (200 mg/m 2) and performed ASCT, hematopoiesis recovered 15 days after stem cell infusion.

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supporting

confidence: 89%

mentioning

confidence: 99%

Autologous hematopoietic stem cell infusion for sustained myelosuppression after BCMA–CAR-T therapy in patient with relapsed myeloma

Lin

Liu

Han

et al. 2019

Bone Marrow Transplant

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“…However, depending on the target population size and total event count, FC-based approaches can be less sensitive. Additionally, cytopenia that occurs frequently after CART treatment [ 1 , 11 , 23 , 24 , 25 ] results in insufficient PBMC numbers to accurately perform FC analysis. Therefore, CART monitoring based on PCR approaches is preferred over FC.…”

Section: Discussionmentioning

confidence: 99%

Assessment of CAR T Cell Frequencies in Axicabtagene Ciloleucel and Tisagenlecleucel Patients Using Duplex Quantitative PCR

Schubert

Kunz

Schmitt

et al. 2020

Cancers

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Chimeric antigen receptor (CAR) T cell (CART) therapy has been established as a treatment option for patients with CD19-positive lymphoid malignancies in both the refractory and the relapsed setting. Displaying significant responses in clinical trials, two second-generation CART products directed against CD19, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), have been approved and integrated into the clinical routine. However, experimental assay for quantitative monitoring of both of these CART products in treated patients in the open domain are lacking. To address this issue, we established and validated a quantitative single copy gene (SCG)-based duplex (DP)-PCR assay (SCG-DP-PCR) to quantify CARTs based on the FMC63 single chain variable fragment (scFv), i.e., axi-cel and tisa-cel. This quantitative PCR (qPCR) approach operates without standard curves or calibrator samples, offers a tool to assess cellular kinetics of FMC63 CARTs and allows direct comparison of CART-copies in axi-cel versus tisa-cel patient samples. For treating physicians, SCG-DP-PCR is an important tool to monitor CARTs and guide clinical decisions regarding CART effects in respective patients.

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“…In addition, the establishment of effective recognition and the management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) caused by CAR T treatment, as well as the understanding of the recurrence and resistance mechanisms, were also mainly derived from the clinical practice of CAR T-19. 2,[19][20][21][22][23] In China, there are 173 registered CAR T trials involving CD19 so far. The first clinical trial targeting CD19 in China was initiated by the PLAGH team in May 2013 for relapsed and/or chemotherapy refractory B-cell malignancies.…”

Section: Hematological Malignancies Cd19mentioning

confidence: 99%

Clinical development of CAR T cell therapy in China: 2020 update

et al. 2020

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Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in the treatment of hematological malignancies. In recent years, fast-growing CAR T clinical trials have actively explored their potential application scenarios. According to the data from the clinicaltrials.gov website, China became the country with the most registered CAR T trials in September 2017. As of June 30, 2020, the number of registered CAR T trials in China has reached 357. In addition, as many as 150 other CAR T trials have been registered on ChiCTR. Although CAR T therapy is flourishing in China, there are still some problems that cannot be ignored. In this review, we aim to systematically summarize the clinical practice of CAR T-cell therapy in China. This review will provide an informative reference for colleagues in the field, and a better understanding of the history and current situation will help us more reasonably conduct research and promote cooperation.

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Early and late hematologic toxicity following CD19 CAR-T cells

Cited by 317 publications

References 29 publications

Autologous hematopoietic stem cell infusion for sustained myelosuppression after BCMA–CAR-T therapy in patient with relapsed myeloma

Autologous hematopoietic stem cell infusion for sustained myelosuppression after BCMA–CAR-T therapy in patient with relapsed myeloma

Assessment of CAR T Cell Frequencies in Axicabtagene Ciloleucel and Tisagenlecleucel Patients Using Duplex Quantitative PCR

Clinical development of CAR T cell therapy in China: 2020 update

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