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嵌合抗原受体 T 细胞(CAR-T)治疗后持续性中性粒细胞减少症的造血干细胞增强:GLA/DRST 研究。

Hematopoietic stem cell boost for persistent neutropenia after CAR T-cell therapy: a GLA/DRST study.

机构信息

Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Hämatologie und Medizinische Onkologie, UM Göttingen, Göttingen, Germany.

出版信息

Blood Adv. 2023 Feb 28;7(4):555-559. doi: 10.1182/bloodadvances.2022008042.


DOI:10.1182/bloodadvances.2022008042
PMID:35696759
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9984300/
Abstract

Hematotoxicity after chimeric antigen receptor (CAR) T-cell therapy is associated with infection and death but management remains unclear. We report results of 31 patients receiving hematopoietic stem cell boost (HSCB; 30 autologous, 1 allogeneic) for either sustained severe neutropenia of grade 4 (<0.5 × 109/L), sustained moderate neutropenia (≤1.5 × 109/L) and high risk of infection, or neutrophil count ≤2.0 × 109/L and active infection. Median time from CAR T-cell therapy to HSCB was 43 days and median absolute neutrophil count at time of HSCB was 0.2. Median duration of neutropenia before HSCB was 38 days (range, 7-151). Overall neutrophil response rate (recovery or improvement) was observed in 26 patients (84%) within a median of 9 days (95% confidence interval, 7-14). Time to response was significantly associated with the duration of prior neutropenia (P = .007). All nonresponders died within the first year after HSCB. One-year overall survival for all patients was 59% and significantly different for neutropenia (≤38 days; 85%) vs neutropenia >38 days before HSCB (44%; P = .029). In conclusion, early or prophylactic HSCB showed quick response and improved outcomes for sustained moderate to severe neutropenia after CAR-T.

摘要

嵌合抗原受体(CAR)T 细胞治疗后的血液毒性与感染和死亡有关,但管理仍不清楚。我们报告了 31 例接受造血干细胞增强(HSCB;30 例自体,1 例异体)的患者结果,这些患者要么持续出现 4 级严重中性粒细胞减少症(<0.5×109/L),要么持续出现中度中性粒细胞减少症(≤1.5×109/L)且存在感染高风险,要么中性粒细胞计数≤2.0×109/L 且存在活动性感染。从 CAR-T 细胞治疗到 HSCB 的中位时间为 43 天,HSCB 时的绝对中性粒细胞计数中位数为 0.2。在接受 HSCB 之前,中性粒细胞减少症的中位持续时间为 38 天(范围,7-151)。在中位数为 9 天(95%置信区间,7-14)内,26 例患者(84%)观察到总体中性粒细胞反应率(恢复或改善)。反应时间与之前中性粒细胞减少症的持续时间显著相关(P=.007)。所有无反应者均在 HSCB 后一年内死亡。所有患者的 1 年总生存率为 59%,HSCB 前中性粒细胞减少症持续时间≤38 天的患者与中性粒细胞减少症持续时间>38 天的患者(44%;P=.029)显著不同。总之,早期或预防性 HSCB 显示出在 CAR-T 后持续中度至重度中性粒细胞减少症时快速反应和改善结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4734/9984300/f17b651987e8/BLOODA_ADV-2022-008042-gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4734/9984300/f17b651987e8/BLOODA_ADV-2022-008042-gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4734/9984300/f17b651987e8/BLOODA_ADV-2022-008042-gr1.jpg

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[5]
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[6]
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[7]
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本文引用的文献

[1]
GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany.

Blood. 2022-7-28

[2]
'Save the day with a Stem Cell Rescue': Use of autologous hematopoietic stem cell boost for hematopoietic recovery after CAR T cell therapy.

Bone Marrow Transplant. 2022-3

[3]
Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL: a noncomparative cohort analysis.

Blood Adv. 2022-1-25

[4]
Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy.

Blood Adv. 2022-4-12

[5]
CAR-HEMATOTOX: a model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma.

Blood. 2021-12-16

[6]
Prolonged hematologic toxicity following treatment with chimeric antigen receptor T cells in patients with hematologic malignancies.

Am J Hematol. 2021-4-1

[7]
Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies.

Blood Adv. 2020-8-11

[8]
Feasibility and Safety of CD19 Chimeric Antigen Receptor T Cell Treatment for B Cell Lymphoma Relapse after Allogeneic Hematopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant. 2020-9

[9]
Successful treatment of marrow failure after CARTs for myeloma by the infusion of cryopreserved stem cells.

Am J Hematol. 2020-1

[10]
Late Events after Treatment with CD19-Targeted Chimeric Antigen Receptor Modified T Cells.

Biol Blood Marrow Transplant. 2020-1

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