干旱区生态环境知识资源中心(Arid): Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells

Arid

DOI	10.1136/jitc-2020-001052
	Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells
	Willier, Semjon; Raedler, Johannes; Blaeschke, Franziska; Stenger, Dana; Escudero, Montserrat Pazos; Jurgeleit, Florian; Grunewald, Thomas G. P.; Binder, Vera; Schmid, Irene; Albert, Michael H.; Wolf, Armin; Feuchtinger, Tobias
通讯作者	Feuchtinger, T
来源期刊	JOURNAL FOR IMMUNOTHERAPY OF CANCER
EISSN	2051-1426
出版年	2020
卷号	8 期号:2
英文摘要	Background Relapsed/refractory B-precursor acute lymphoblastic leukemia (BCP-ALL) remains a major therapeutic challenge in pediatric hematology. Chimeric antigen receptor (CAR) T cells targeting CD19 have shown remarkable initial response rates in BCP-ALL patients, while long-term leukemia control rate is only about 50%. So far, main mechanisms of BCP-ALL relapse after CD19-CAR T-cell therapy have been either insufficient CAR T-cell persistence in vivo or loss of surface CD19. Case Report Here, we report an exceptional presentation of BCP-ALL relapse in the eye during the systemic control through CAR T-cell therapy. We report a case of fatal intraocular relapse in a pediatric patient with pro-B-ALL after initial response to CD19-CAR T-cell therapy. One month after CD19-CAR T-cell therapy, remission was documented by bone marrow aspirate analysis with absence of CD19(+)cells and CD19-CAR T cells could be detected in both peripheral blood and bone marrow. At the same time, however, the patient presented with progressive visual disturbance and CD19(+)cells were found within the anterior chamber of the eye. Despite local and systemic therapy, ocular relapse led to BCP-ALL dissemination and systemic relapse within weeks. The eye represents a rare site for local manifestation of BCP-ALL, but isolated intraocular relapse is a clinically unreckoned presentation of BCP-ALL in the era of CD19-CAR T cells. Conclusion During systemic control of BCP-ALL through CD19-CAR T cells, relapse can emerge in the eye as an immune-privileged organ. Ocular symptoms after CD19-CAR T-cell therapy should guide the clinician to elucidate the etiology in a timely fashion in order to adjust leukemia treatment strategy. Both, local immune escape as well as insufficient CAR T-cell persistence may have contributed to relapse in the reported patient. Mechanisms of relapse in an immune desert under CAR T-cell therapy require future clinical and experimental attention. In particular, ocular symptoms after CAR T-cell therapy should be considered a potentially early sign of leukemia relapse.
英文关键词	receptors chimeric antigen immunotherapy adoptive pediatrics tumor escape T-Lymphocytes
类型	Article
语种	英语
开放获取类型	gold, Green Published
收录类别	SCI-E
WOS记录号	WOS:000576255600002
WOS关键词	OPHTHALMIC MANIFESTATIONS ; PRIVILEGE
WOS类目	Oncology ; Immunology
WOS研究方向	Oncology ; Immunology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/326679
作者单位	[Willier, Semjon; Raedler, Johannes; Blaeschke, Franziska; Stenger, Dana; Jurgeleit, Florian; Binder, Vera; Schmid, Irene; Albert, Michael H.; Feuchtinger, Tobias] Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Univ Hosp, Pediat Hematol Oncol Hemostaseol & Stem Cell Tran, Munich, Germany; [Stenger, Dana; Grunewald, Thomas G. P.] German Canc Res Ctr, Heidelberg, Germany; [Escudero, Montserrat Pazos] Ludwig Maximilian Univ Munich, Univ Hosp Munich, Dept Radiotherapy, Munich, Germany; [Grunewald, Thomas G. P.] Ludwig Maximilians Univ Munchen, Inst Pathol, Fac Med, Munich, Germany; [Grunewald, Thomas G. P.] Ludwig Maximilians Univ Munchen, Inst Pathol, Fac Med, Max Eder Res Grp Pediat Sarcoma Biol, Munich, Germany; [Grunewald, Thomas G. P.] German Canc Consortium DKTK, Partner Site Munich, Munich, Germany; [Wolf, Armin] Ludwig Maximilian Univ Munich, Univ Hosp Munich, Dept Ophthalmol, Munich, Germany; [Wolf, Armin] Univ Ulm, Dept Ophthalmol, Ulm, Germany
推荐引用方式 GB/T 7714	Willier, Semjon,Raedler, Johannes,Blaeschke, Franziska,et al. Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells[J],2020,8(2).
APA	Willier, Semjon.,Raedler, Johannes.,Blaeschke, Franziska.,Stenger, Dana.,Escudero, Montserrat Pazos.,...&Feuchtinger, Tobias.(2020).Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells.JOURNAL FOR IMMUNOTHERAPY OF CANCER,8(2).
MLA	Willier, Semjon,et al."Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells".JOURNAL FOR IMMUNOTHERAPY OF CANCER 8.2(2020).