Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy

被引：619

作者：

Gardner, Rebecca ^{[1
,2
]}

Wu, David ^{[3
]}

Cherian, Sindhu ^{[3
]}

Fang, Min ^{[3
]}

Hanafi, Laila-Aicha ^{[4
,5
]}

Finney, Olivia ^{[1
]}

Smithers, Hannah ^{[1
]}

Jensen, Michael C. ^{[1
,2
]}

Riddell, Stanley R. ^{[4
,5
]}

Maloney, David G. ^{[4
,5
]}

Turtle, Cameron J. ^{[4
,5
]}

机构：

[1] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA

[2] Univ Washington, Dept Pediat, Seattle, WA 98195 USA

[3] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA

[4] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA

[5] Univ Washington, Dept Med, Seattle, WA USA

来源：

BLOOD | 2016年 / 127卷 / 20期

基金：

美国国家卫生研究院;

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA;

D O I：

10.1182/blood-2015-08-665547

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Administration of lymphodepletion chemotherapy followed by CD19-specific chimeric antigen receptor (CAR)-modified T cells is a remarkably effective approach to treating patients with relapsed and refractory CD19 1 B-cell malignancies. We treated 7 patients with B-cell acute lymphoblastic leukemia (B-ALL) harboring rearrangement of the mixed lineage leukemia (MLL) gene with CD19 CAR-T cells. All patients achieved complete remission (CR) in the bone marrow by flow cytometry after CD19 CAR-T-cell therapy; however, within 1 month of CAR-T-cell infusion, 2 of the patients developed acute myeloid leukemia (AML) that was clonally related to their B-ALL, a novel mechanism of CD19-negative immune escape. These reports have implications for the management of patients with relapsed and refractory MLL-B-ALL who receive CD19 CAR-T-cell therapy.

引用

页码：2406 / 2410

页数：5

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