DESCAR-T登记处CAR T细胞治疗后的T细胞恶性肿瘤-动脉网

T cell malignancies after CAR T cell therapy in the DESCAR-T registry

Nature 等信源发布 2025-01-08 18:53



可切换为仅中文







Abstract

摘要

The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018.

嵌合抗原受体（CAR）T细胞治疗后T细胞恶性肿瘤的风险令人担忧，尽管真正的发病率仍不清楚。在这里，我们分析了DESCAR-T登记数据库，其中包括自2018年7月1日以来在法国接受CAR T细胞治疗的所有儿科和成人恶性血液病患者。

Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.8%) received axicabtagene ciloleucel, 205 (6.7%) brexucabtagene autoleucel, 44 (1.4%) lisocabtagene maraleucel and 769 (25.1%) tisagenlecleucel. All multiple myeloma patients received idecabtagene vicleucel, with none receiving ciltacabtagene autoleucel.

在3066例患者中（2536例B细胞淋巴瘤，162例B细胞急性淋巴细胞白血病（ALL）和368例多发性骨髓瘤），1680例（54.8%）接受了axicabtagene ciloleucel，205例（6.7%）brexucabtagene autoleucel，44例（1.4%）liscobatagene maraluel和769例（25.1%）tisagenlecleucel。所有多发性骨髓瘤患者均接受idecabtagene-vicleucel治疗，无一例接受ciltacabtagene-autoleucel治疗。

After a median follow-up of 12.7 months for B cell lymphoma, 17.7 months for B cell ALL and 6.3 months for multiple myeloma, only one (0.03%) patient developed a T cell malignancy after CAR T infusion. Specifically, the patient was diagnosed with a primary cutaneous CD30.

在B细胞淋巴瘤中位随访12.7个月，B细胞ALL中位随访17.7个月，多发性骨髓瘤中位随访6.3个月后，只有一名（0.03%）患者在CAR T输注后发生T细胞恶性肿瘤。具体而言，该患者被诊断出患有原发性皮肤CD30。

T cell lymphoproliferative disorder (anaplastic lymphoma kinase-negative) 3 years after receiving tisagenlecleucel therapy for diffuse large B cell lymphoma. This was associated with the integration of a CAR clone into the tumor suppressor gene

接受tisagenlecleucel治疗弥漫性大B细胞淋巴瘤3年后，T细胞淋巴增生性疾病（间变性淋巴瘤激酶阴性）。这与CAR克隆整合到肿瘤抑制基因中有关

PLAAT4

地点4

(phospholipase A and acyltransferase 4). Thus, the development of this secondary T cell malignancy might be linked to the use of CAR T cell therapy. In conclusion, our findings indicate a very low risk of T cell malignancy after CAR T cell therapy.

（磷脂酶A和酰基转移酶4）。因此，这种继发性T细胞恶性肿瘤的发展可能与使用CAR T细胞疗法有关。总之，我们的研究结果表明，CAR T细胞治疗后T细胞恶性肿瘤的风险非常低。

Access through your institution

通过您的机构访问

Buy or subscribe

购买或订阅

This is a preview of subscription content,

这是订阅内容的预览，

access via your institution

通过您的机构访问

Access options

访问选项

Access through your institution

通过您的机构访问

Access through your institution

通过您的机构访问

Change institution

变革机构

Buy or subscribe

购买或订阅

Access Nature and 54 other Nature Portfolio journals

Access Nature和54种其他Nature投资组合期刊

Get Nature+, our best-value online-access subscription

获取Nature+，我们最具价值的在线访问订阅

24,99 €

/ 30 days

/30天

cancel any time

随时取消

Learn more

了解更多信息

Subscription info for Chinese customers

中国客户的订阅信息

We have a dedicated website for our Chinese customers. Please go to

我们有一个专门为中国客户服务的网站。请转到

naturechina.com

to subscribe to this journal.

订阅此日记。

Go to naturechina.com

访问naturechina.com

Buy this article

购买这篇文章

Purchase on SpringerLink

在SpringerLink上购买

Instant access to full article PDF

即时访问全文PDF

Buy now

立即购买

Prices may be subject to local taxes which are calculated during checkout

价格可能需要缴纳结帐时计算的地方税

Additional access options:

其他访问选项：

Learn about institutional subscriptions

了解机构订阅

Read our FAQs

阅读我们的常见问题

Contact customer support

联系客户支持

Fig. 1: Cumulative incidence of T cell malignancy after commercial CAR T cell therapy in the French DESCAR-T registry.

图1：法国DESCAR-T登记处商业CAR T细胞治疗后T细胞恶性肿瘤的累积发生率。

Data availability

数据可用性

Data from the DESCAR-T registry is subject to controlled access by the LYSARC and the IFM due to privacy, legal and proprietary requirements. Requests for individual deidentified participant data will be reviewed promptly by the corresponding author and the DESCAR-T scientific committee, and data will be shared by the LYSARC and the IFM once an appropriate Data Transfer Agreement (DTA) is in place.

由于隐私、法律和专有要求，来自DESCAR-T注册表的数据受LYSARC和IFM的控制访问。通讯作者和DESCAR-T科学委员会将立即审查对个人身份不明参与者数据的请求，一旦适当的数据传输协议（DTA）到位，数据将由LYSARC和IFM共享。

Individual deidentified participant data will be made available for replication and validation purposes for the present study only. For any other purposes, access to DESCAR-T data will depend on the nature of the request, the intended use of the data and their availability, as well as the merit of the research project.

个人身份不明的参与者数据将仅用于本研究的复制和验证目的。出于任何其他目的，对DESCAR-T数据的访问将取决于请求的性质，数据的预期用途及其可用性，以及研究项目的优点。

If the project is validated by the registry’s partner groups in oncology and the DESCAR-T scientific committee, an appropriate DTA must be signed before any data transfer. The DTA will include data protection rules, the responsibilities of each party, data security and storage information. All requests should be addressed to descar-t@lysarc.org, and a response will be provided within 1 month of the data request..

如果该项目得到登记处肿瘤学合作伙伴小组和DESCAR-T科学委员会的验证，则必须在任何数据传输之前签署适当的DTA。DTA将包括数据保护规则、各方的责任、数据安全和存储信息。所有请求均应发送至descar-t@lysarc.org，并且将在数据请求的1个月内提供响应。。

References

参考文献

Furlow, B. FDA investigates risk of secondary lymphomas after CAR-T immunotherapy.

Furlow，B。FDA调查了CAR-T免疫治疗后继发性淋巴瘤的风险。

Lancet Oncol.

柳叶刀Oncol。

, 21 (2024).

Article

文章

PubMed

Google Scholar

谷歌学者

Verdun, N. & Marks, P. Secondary cancers after chimeric antigen receptor T-cell therapy.

Verdun，N。＆Marks，P。嵌合抗原受体T细胞治疗后的继发性癌症。

N. Engl. J. Med.

N.Engl。医学杂志。

390

, 584–586 (2024).

Article

文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Harrison, S. J. et al. CAR

Harrison，S.J.等人

T-cell lymphoma post ciltacabtagene autoleucel therapy for relapsed refractory multiple myeloma.

西他卡宾自体白血病治疗复发难治性多发性骨髓瘤后的T细胞淋巴瘤。

Blood

血液

142

, 6939 (2023).

Article

文章

Google Scholar

谷歌学者

Ghilardi, G. et al. T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy.

Ghilardi，G。等人。商业CAR T细胞治疗后的T细胞淋巴瘤和继发性原发性恶性肿瘤风险。

Nat. Med.

自然医学。

, 984–989 (2024).

Article

文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Ozdemirli, M. et al. Indolent CD4

Ozdemirli，M.等人.惰性CD4

CAR T-cell lymphoma after cilta-cel CAR T-cell therapy.

cilta细胞CAR T细胞治疗后的CAR T细胞淋巴瘤。

N. Engl. J. Med.

N.Engl。医学杂志。

390

, 2074–2082 (2024).

Article

文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Hamilton, M. P. et al. Risk of second tumors and T-cell lymphoma after CAR T-cell therapy.

Hamilton，M.P.等人。CAR T细胞治疗后第二次肿瘤和T细胞淋巴瘤的风险。

N. Engl. J. Med.

N.Engl。医学杂志。

390

, 2047–2060 (2024).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Elsallab, M. et al. Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA Adverse Events Reporting System.

Elsallab，M.等。商业CAR T细胞治疗后的第二原发性恶性肿瘤：FDA不良事件报告系统的分析。

Blood

血液

143

, 2099–2105 (2024).

Article

文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Storgard, R., Rejeski, K., Perales, M. A., Goldman, A. & Shouval, R. T-cell malignant neoplasms after chimeric antigen receptor T-cell therapy.

Storgard，R.，Rejeski，K.，Perales，M.A.，Goldman，A。＆Shouval，R。嵌合抗原受体T细胞治疗后的T细胞恶性肿瘤。

JAMA Oncol.

JAMA肿瘤学。

, 826–828 (2024).

Article

文章

PubMed

Google Scholar

谷歌学者

Einkauf, K. B. et al. Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses.

Einkauf，K.B.等人。单个HIV-1原病毒转录，整合和序列的平行分析。

Cell

细胞

185

, 266–282.e15 (2022).

，266-282.e15（2022）。

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wagner, T. A. et al. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection.

Wagner，T.A。等人。整合到癌症基因中的HIV细胞的增殖有助于持续感染。

Science

科学

345

, 570–573 (2014).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cole, B. et al. In-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia.

Cole，B。等人。对具有翻译能力的HIV-1储库的深入单细胞分析可确定血浆病毒血症的细胞来源。

Nat. Commun.

Nat.普通。

, 3727 (2021).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhao, J. Y. et al. Phospholipase A and acyltransferase 4/retinoic acid receptor responder 3 at the intersection of tumor suppression and pathogen restriction.

Zhao，J.Y.等人。磷脂酶A和酰基转移酶4/视黄酸受体应答器3在肿瘤抑制和病原体限制的交叉点。

Front Immunol.

前免疫。

, 1107239 (2023).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Casanova, B. et al. The class II tumor-suppressor gene RARRES3 is expressed in B cell lymphocytic leukemias and down-regulated with disease progression.

Casanova，B。等人。II类肿瘤抑制基因RARRES3在B细胞淋巴细胞白血病中表达，并随着疾病进展而下调。

Leukemia

白血病

, 1521–1526 (2001).

Article

文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Mustafa, N. et al. VS-5584 mediates potent anti-myeloma activity via the upregulation of a class II tumor suppressor gene, RARRES3 and the activation of Bim.

Mustafa，N。等人VS-5584通过上调II类肿瘤抑制基因RARRES3和激活Bim介导有效的抗骨髓瘤活性。

Oncotarget

肿瘤靶点

, 101847–101864 (2017).

Article

文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Tsai, F. M., Shyu, R. Y. & Jiang, S. Y. RIG1 suppresses Ras activation and induces cellular apoptosis at the Golgi apparatus.

Tsai，F.M.，Shyu，R.Y。＆Jiang，S.Y。RIG1抑制Ras活化并诱导高尔基体细胞凋亡。

Cell Signal.

细胞信号。

, 989–999 (2007).

Article

文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Golczak, M. et al. Structural basis for the acyltransferase activity of lecithin:retinol acyltransferase-like proteins.

Golczak，M.等人。卵磷脂酰基转移酶活性的结构基础：视黄醇酰基转移酶样蛋白。

J. Biol. Chem.

J.生物学。化学。

287

, 23790–23807 (2012).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fraietta, J. A. et al. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells.

Fraietta，J.A。等人。TET2的破坏促进了CD19靶向T细胞的治疗功效。

Nature

自然

558

, 307–312 (2018).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Miller, P. G. et al. Clonal hematopoiesis in patients receiving chimeric antigen receptor T-cell therapy.

Miller，P.G.等人。接受嵌合抗原受体T细胞治疗的患者的克隆造血。

Blood Adv.

血液高级。

, 2982–2986 (2021).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Panagiota, V. et al. Clinical implications and dynamics of clonal hematopoiesis in anti-CD19 CAR T-cell treated patients.

Panagiota，V。等人。抗CD19 CAR T细胞治疗患者克隆造血的临床意义和动力学。

HemaSphere

血球

, e957 (2023).

，e957（2023）。

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Teipel, R. et al. Prevalence and variation of CHIP in patients with aggressive lymphomas undergoing CD19-directed CAR T-cell treatment.

Teipel，R.等人。接受CD19指导的CAR T细胞治疗的侵袭性淋巴瘤患者中CHIP的患病率和变异。

Blood Adv.

血液高级。

, 1941–1946 (2022).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Levine, B. L. et al. Unanswered questions following reports of secondary malignancies after CAR-T cell therapy.

Levine，B.L.等人在CAR-T细胞治疗后继发性恶性肿瘤的报道后未回答的问题。

Nat. Med.

自然医学。

, 338–341 (2024).

Article

文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Meadows, A. T. et al. Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort.

Meadows，A.T.等人，《儿童癌症幸存者的第二种肿瘤：儿童癌症幸存者研究队列的发现》。

J. Clin. Oncol.

J、克林。肿瘤。

, 2356–2362 (2009).

Article

文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Schaapveld, M. et al. Second cancer risk up to 40 years after treatment for Hodgkin’s lymphoma.

Schaapveld，M.等人。霍奇金淋巴瘤治疗40年后的第二次癌症风险。

N. Engl. J. Med.

N.Engl。医学杂志。

373

, 2499–2511 (2015).

Article

文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Bhatia, S. et al. Trends in late mortality and life expectancy after autologous blood or marrow transplantation over three decades: a BMTSS report.

Bhatia，S.等人，《三十年来自体血液或骨髓移植后晚期死亡率和预期寿命的趋势：BMTSS报告》。

J. Clin. Oncol.

J、克林。肿瘤。

, 1991–2003 (2022).

Article

文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download references

下载参考资料

Acknowledgements

致谢

We would like to extend our deepest gratitude to all the patients who participated in this study, the dedicated staff at all participating centers, the Lymphoma Academic Research Organisation (LYSARC) and the cooperative groups and scientific societies involved: the Intergroupe Francophone du myélome (IFM), the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL), the LYmphoma Study Association (LYSA), the French Society for the Fight Against Cancers and Leukemias in Children and Adolescents (SFCE) and the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC).

我们要向所有参与这项研究的患者，所有参与中心的专职工作人员，淋巴瘤学术研究组织（LYSARC）以及参与的合作团体和科学协会表示最深切的感谢：法语国家小组（IFM），成人急性淋巴细胞白血病研究小组（GRAALL），淋巴瘤研究协会（LYSA），法国儿童和青少年癌症和白血病防治协会（SFCE）和法语国家骨髓移植和细胞治疗协会（SFGM-TC）。

We are especially thankful to A. Marquet, K. Danno, É. Gat, V. Dupont, P. Cony-Makhoul, È. Gehlkopf and M.-O. Petillon for their considerable dedication and support. We also gratefully acknowledge the invaluable contributions of the following principal investigators: J. Abraham, Y. Bertrand, P. Bories, D.

我们特别感谢A.Marquet，K.Danno，É。盖特（Gat），杜邦（V.Dupont），康尼（P.Cony Makhoul），È。Gehlkopf和M.-O.Petillon的奉献和支持。我们也非常感谢以下主要调查人员的宝贵贡献：J.Abraham，Y.Bertrand，P.Bories，D。

Blaise, N. Buchbinder, S. Carras, C. Castilla Llorente, G. Cartron, A. Chauchet, J. Decroocq, G.L. Damaj, A. Durand, L. Fouillet, T. Gastinne, F.-X. Gros, G. Guillerm, B. Guffroy, E. Gyan, O. Hermine, M. Joris, F. Jardin, F. Le Bras, X. Leleu, J.-V. Malfuson, S. Maury, M. Mohty, F. Morschhauser, E. Nicolas-Virelizier, C.

Blaise，N.Buchbinder，S.Carras，C.Castilla Llorente，G.Cartron，A.Chauchet，J.Decroocq，G.L.Damaj，A.Durand，L.Fouillet，T.Gastinne，F.-X.Gros，G.Guillerm，B.Guffroy，E.Gyan，O.Hermine，M.Joris，F.Jardin，F.Le Bras，X.Leleu，J.-V.Malfuson，S.Maury，M.Mohty，F.Morschhauser，E.Nicolas Virelizier，C。

Pochon, M.-T. Rubio, A. Sterin, A. Tanguy-Schmidt and I. Yakoub-Agha. We appreciate their commitment and contributions to this collaborative effort. Finally, we received no specific funding for this work..

Pochon，M.-T.Rubio，A.Sterin，A.Tanguy Schmidt和I.Yakoub Agha。我们赞赏他们对这一合作努力的承诺和贡献。最后，我们没有收到这项工作的具体资金。。

Author information

作者信息

Author notes

作者笔记

These authors contributed equally: Remy Dulery, Vincent Guiraud, Sylvain Choquet.

这些作者做出了同样的贡献：雷米·杜勒里，文森特·吉劳德，西尔文·乔奎特。

Authors and Affiliations

作者和隶属关系

Department of Clinical Hematology and Cellular Therapy, Sorbonne University, Hôpital Saint-Antoine, Assistance Publique—Hôpitaux de Paris, INSERM, UMRs 938, Centre de recherche Saint-Antoine (CRSA), Paris, France

索邦大学临床血液学和细胞治疗系，圣安托万医院，巴黎公共医院，INSERM，UMRs 938，巴黎圣安托万研究中心（CRSA）

Remy Dulery

薪酬

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

美国马萨诸塞州波士顿哈佛医学院达纳·法伯癌症研究所肿瘤内科

Remy Dulery

薪酬

Department of Virology, Sorbonne University, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique (IPLESP), Assistance Publique—Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France

索邦大学病毒学系、Inserm、皮埃尔·路易斯流行病学和公共卫生研究所（IPLESP）、公共援助-巴黎医院、法国巴黎Pitié-Salpêtrière医院

Vincent Guiraud & Ève Todesco

文森特·吉罗_埃维·托德斯科

Department of Clinical Hematology, Sorbonne University, Hôpital Pitié-Salpêtrière, Assistance Publique—Hôpitaux de Paris, Paris, France

索邦大学临床血液学系，Pitié-Salpêtrière医院，公共援助-巴黎医院，巴黎，法国

Sylvain Choquet

Hemato-oncology, Paris Cité University, Assistance Publique—Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France

血液肿瘤学，巴黎城市大学，公共援助-巴黎医院，圣路易斯医院，巴黎，法国

Catherine Thieblemont

凯瑟琳·蒂博蒙特

Hematology Department, Hospices Civils de Lyon, Pierre-Bénite, France

法国皮埃尔·贝尼特里昂市民医院血液科

Emmanuel Bachy

Unit of Dermatology, Sorbonne University, Hôpital Pitié-Salpêtrière, Assistance Publique—Hôpitaux de Paris, Paris, France

索邦大学皮肤科，Pitié-Salpêtrière医院，公共援助-巴黎医院，巴黎，法国

Stéphane Barete

斯特凡·巴雷特

Department of Immuno-Hematology, Paris Cité University, Hôpital Saint-Louis, Assistance Publique—Hôpitaux de Paris, Paris, France

巴黎城市大学免疫血液学系，圣路易斯医院，公共援助-巴黎医院，巴黎，法国

Bertrand Arnulf

Hematology Adolescents and Young Adult Unit, Paris Cité University, Hôpital Saint-Louis, Assistance Publique—Hôpitaux de Paris, URP-3518, Institut de Recherche Saint-Louis, Paris, France

血液学青少年和年轻人股，巴黎城市大学，圣路易斯医院，公共援助-巴黎医院，URP-3518，圣路易斯研究所，巴黎，法国

Nicolas Boissel

尼古拉斯·布瓦塞尔

Department of Pediatric Hematology and Immunology, Paris Cité University, Hôpital Universitaire Robert Debré, Assistance Publique—Hôpitaux de Paris, EA3518, Institut de Recherche Saint-Louis, Paris, France

巴黎城市大学儿科血液学和免疫学系，罗伯特·德布雷大学医院，公共援助-巴黎医院，EA3518，法国巴黎圣路易斯研究所

André Baruchel

安德烈·巴鲁切尔

Department of Adult Clinical Hematology and Cellular Therapy, CHU Clermont-Ferrand, Clermont-Ferrand, France

成人临床血液学和细胞治疗系，CHU Clermont Ferrand，Clermont Ferrand，法国

Jacques-Olivier Bay

雅克·奥利维尔湾

Department of Hematology, Versailles Saint-Quentin University, Institut Curie, Laboratoire d’Imagerie Translationnelle en Oncologie (LITO), U1288 Inserm/Institut Curie Centre de recherche, Saint-Cloud, France

凡尔赛-圣昆廷大学血液学系，居里研究所，肿瘤转化成像实验室（LITO），U1288 Inserm/居里研究院研究中心，法国圣克劳德

Steven Le Gouill

史蒂文·勒·古伊尔

Department of Hematology, University Hospital of Rennes, UMR U1236, INSERM, University of Rennes, French Blood Establishment, Rennes, France

雷恩大学医院血液科，UMR U1236，INSERM，雷恩大学，法国雷恩血液研究所

Roch Houot

Authors

作者

Remy Dulery

薪酬

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Vincent Guiraud

文森特·吉罗

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Sylvain Choquet

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Catherine Thieblemont

凯瑟琳·蒂博蒙特

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Emmanuel Bachy

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Stéphane Barete

斯特凡·巴雷特

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Ève Todesco

埃韦·托德斯科

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Bertrand Arnulf

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Nicolas Boissel

尼古拉斯·布瓦塞尔

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

André Baruchel

安德烈·巴鲁切尔

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Jacques-Olivier Bay

雅克·奥利维尔湾

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Steven Le Gouill

史蒂文·勒·古伊尔

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Roch Houot

View author publications

查看作者出版物

You can also search for this author in

您也可以在中搜索此作者

PubMed

Google Scholar

谷歌学者

Contributions

捐款

R.D. designed the study, recruited patients, analyzed data and wrote the manuscript. R.H. designed the study, recruited patients, supervised research, analyzed data and commented on the manuscript. V.G. performed and interpreted the CAR integration site analysis and commented on the manuscript. S.C.

R、 D.设计研究，招募患者，分析数据并撰写手稿。R、 H.设计研究，招募患者，监督研究，分析数据并对手稿进行评论。五、 G.执行并解释了CAR集成站点分析，并对手稿进行了评论。S、 C。

recruited patients, provided care to the patients with primary cutaneous CD30.

招募患者，为原发性皮肤CD30患者提供护理。

T cell lymphoproliferative disorder and commented on the manuscript. S.B. provided care to the patients with primary cutaneous CD30

T细胞淋巴组织增生性疾病，并对手稿进行了评论。S、 B.为原发性皮肤CD30患者提供护理

T cell lymphoproliferative disorder, evaluated histopathological samples and commented on the manuscript. E.T. performed and interpreted sequencing analysis and commented on the manuscript. C.T., E.B., B.A., N.B., A.B., J.-O.B. and S.L.G. recruited patients and commented on the manuscript. All authors reviewed the manuscript and approved its submission for publication purposes..

T细胞淋巴组织增生性疾病，评估组织病理学样本并对手稿进行评论。E、 T.进行并解释了测序分析，并对手稿进行了评论。C、 T.，E.B.，B.A.，N.B.，A.B.，J.-O.B.和S.L.G.招募了患者并对手稿进行了评论。所有作者都审阅了手稿，并批准了其提交以供出版。。

Corresponding author

通讯作者

Correspondence to

通信对象

Remy Dulery

薪酬

Ethics declarations

道德宣言

Competing interests

相互竞争的利益

R.D. reports research funding from Ligue Contre le Cancer, Arthur Sachs Scholarship Fund, Monahan Foundation, Servier Foundation, Philippe Foundation and DCP AP-HP; honoraria from Novartis and Takeda; and support for attending meetings and/or travel from Sanofi and Kite Pharma/Gilead. S.C. reports personal fees from Kite Pharma/Gilead, Novartis, Janssen, Celgene-BMS, Takeda, Atara, Astra Zeneca, Pierre Fabre, Viatris and Lilly.

R、 D.报告来自Ligue Contre le Cancer，Arthur Sachs奖学金基金，Monahan基金会，Servier基金会，Philippe基金会和DCP AP-HP的研究资金；诺华和武田的酬金；并支持参加赛诺菲和Kite Pharma/Gilead的会议和/或旅行。S、 C.报告来自Kite Pharma/Gilead，Novartis，Janssen，Celgene BMS，Takeda，Atara，Astra Zeneca，Pierre Fabre，Viatris和Lilly的个人费用。

C.T. reports membership on an entity’s Board of Directors or advisory committees of Kite Pharma/Gilead, Amgen, AbbVie, Novartis, Roche, Gilead Sciences, Takeda, BMS/Celgene, Incyte and Cellectis; consultancy for Kite Pharma/Gilead, Amgen, AbbVie, Novartis, Gilead Sciences, Cellectis, Roche and BMS/Celgene; honoraria from Takeda, Incyte, Bayer, Kite Pharma/Gilead, Novartis, BMS, Abbvie, F.

C、 T.报告Kite Pharma/Gilead，Amgen，AbbVie，Novartis，Roche，Gilead Sciences，Takeda，BMS/Celgene，Incyte和Cellectis的实体董事会或咨询委员会成员；Kite Pharma/Gilead，Amgen，AbbVie，Novartis，Gilead Sciences，Cellectis，Roche和BMS/Celgene的顾问；来自武田，英杰，拜耳，风筝制药/吉利德，诺华，BMS，艾伯维，F。

Hoffmann-La Roche Ltd., Amgen, Cellectis and Janssen; research funding from Hospira and BMS/Celgene; and support for attending meetings and/or travel from Kite Pharma/Gilead, Amgen, AbbVie, Novartis, Gilead Sciences, Cellectis, Roche, BMS/Celgene and Janssen. E.B. reports participation on a data safety monitoring board or advisory board of Novartis, Kite Pharma/Gilead, Roch, Incyte, ADC Therapeutics, Abbvie and Beigene; consultancy for Kite Pharma/Gilead, Amgen, AbbVie, Novartis, Gilead Sciences, Cellectis, Roche and BMS/Celgene; honoraria from Novartis, Kite Pharma/Gilead, Roche, Takeda, Janssen, Abbvie and Astra Zeneca; research funding from Amgen and BMS; and support for attending meetings and/or travel from Roche, Kite Pharma/Gilead and Novartis.

霍夫曼·拉罗氏有限公司，安进，Cellectis和杨森；Hospira和BMS/Celgene的研究资金；并支持参加Kite Pharma/Gilead，Amgen，AbbVie，Novartis，Gilead Sciences，Cellectis，Roche，BMS/Celgene和Janssen的会议和/或旅行。E、 B.报告参与诺华，Kite Pharma/Gilead，Roch，Incyte，ADC Therapeutics，Abbvie和Beigene的数据安全监测委员会或咨询委员会；Kite Pharma/Gilead，Amgen，AbbVie，Novartis，Gilead Sciences，Cellectis，Roche和BMS/Celgene的顾问；诺华，Kite Pharma/Gilead，罗氏，武田，杨森，Abbvie和Astra Zeneca的酬金；安进和BMS的研究资金；并支持参加罗氏，基特制药/吉利德和诺华的会议和/或旅行。

R.H. reports honoraria from Kite Pharma/Gilead, Novartis, Incyte, Janssen, MSD, Takeda, Amgen, Abbvie and Roche; and membership on an entity’s Board of Directors or advisory committees of Kite Pharma/Gilead, Novarti.

R、 H.报告来自Kite Pharma/Gilead，Novartis，Incyte，Janssen，MSD，Takeda，Amgen，Abbvie和Roche的酬金；以及诺华Kite Pharma/Gilead实体董事会或咨询委员会的成员。

Peer review

同行评审

Peer review information

同行评审信息

Nature Medicine

自然医学

thanks Andrea Schmidts and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Ulrike Harjes, in collaboration with the

感谢Andrea Schmidts和另一位匿名审稿人对这项工作的同行评议做出的贡献。主要处理编辑：Ulrike Harjes，与

Nature Medicine

自然医学

team.

团队。

Additional information

其他信息

Publisher’s note

出版商注释

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。

Extended data

扩展数据

Extended Data Fig. 1 Patient clinical course and treatment timeline.

扩展数据图1患者临床病程和治疗时间表。

A 73-year-old woman with stage IV diffuse large B-cell lymphoma (DLBCL), relapsing after two prior lines of chemoimmunotherapy, received CAR T-cell therapy (tisa-cel). She achieved complete remission but developed a CD30 + T-cell lymphoproliferative disorder (T-LPD) 34 months post-infusion, which was successively treated with extracorporeal photochemotherapy (ECP), brentuximab-vedotin (BV), and gemcitabine.

一名患有IV期弥漫性大B细胞淋巴瘤（DLBCL）的73岁女性接受了CAR T细胞治疗（tisa-cell），该患者在两次先前的化学免疫治疗后复发。她达到了完全缓解，但在输注后34个月出现了CD30+T细胞淋巴增生性疾病（T-LPD），先后接受了体外光化学疗法（ECP），brentuximab vedotin（BV）和吉西他滨治疗。

The secondary T-cell malignancy persisted at the last follow-up. .

继发性T细胞恶性肿瘤在最后一次随访中持续存在。

Abbreviations:

缩写：

DLBCL, diffuse large B-cell lymphoma; T-LPD, T-cell lymphoproliferative disorder; LN, lymph node; CSF, cerebrospinal fluid; IL-10, interleukin 10; BM, bone marrow; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; MTX, methotrexate; R-DHAOx, rituximab plus dexamethasone, high-dose cytarabine, and oxaliplatin; BEAM, carmustine, etoposide, cytarabine, and melphalan; auto-HSCT, autologous hematopoietic stem cell transplantation; R-ICE, rituximab plus ifosfamide, carboplatin, and etoposide phosphate; Tisa-cel, tisagenlecleucel; ECP, extracorporeal photochemotherapy; BV, brentuximab-vedotin..

DLBCL，弥漫性大B细胞淋巴瘤；T-LPD，T细胞淋巴增生性疾病；LN，淋巴结；脑脊液，脑脊液；IL-10，白细胞介素10；BM，骨髓；R-CHOP，利妥昔单抗加环磷酰胺，多柔比星，长春新碱和泼尼松；MTX，甲氨蝶呤；R-DHAOx，利妥昔单抗加地塞米松，大剂量阿糖胞苷和奥沙利铂；BEAM，卡莫司汀，依托泊苷，阿糖胞苷和美法仑；自体HSCT，自体造血干细胞移植；R-ICE，利妥昔单抗加异环磷酰胺，卡铂和磷酸依托泊苷；Tisa cel，tisagenlecleucel；ECP，体外光化学疗法；BV，brentuximab vedotin。。

Supplementary information

补充信息

Reporting Summary

报告摘要

Rights and permissions

权限和权限

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law..

Springer Nature或其许可方（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有独家权利；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。。

Reprints and permissions

重印和许可

About this article

关于本文

Cite this article

引用本文

Dulery, R., Guiraud, V., Choquet, S.

杜勒里，R.，吉劳德，V.，Choquet，S。

et al.

等人。

T cell malignancies after CAR T cell therapy in the DESCAR-T registry.