Oncotarget

Research Papers: Immunology:

Persistent donor derived Vδ4 T cell clones may improve survival for recurrent T cell acute lymphoblastic leukemia after HSCT and DLI

Ling Xu, Jianyu Weng, Xin Huang, Chengwu Zeng, Shaohua Chen, Suxia Geng, Lijian Yang, Suijing Wu, Suming Huang, Xin Du and Yangqiu Li _

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Oncotarget. 2016; 7:42943-42952. https://doi.org/10.18632/oncotarget.10260

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Abstract

Ling Xu1,*, Jianyu Weng2,*, Xin Huang2, Chengwu Zeng1, Shaohua Chen1, Suxia Geng2, Lijian Yang1, Suijing Wu2, Suming Huang4, Xin Du2 and Yangqiu Li1,3,5

1 Institute of Hematology, Jinan University, Guangzhou, China

2 Department of Hematology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

3 Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China

4 Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA

5 Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China

* These authors have contributed equally to this work

Correspondence to:

Yangqiu Li, email:

Xin Du, email:

Keywords: T-ALL, T cell repertoire, allo-HSCT, MRD, DLI, Immunology and Microbiology Section, Immune response, Immunity

Received: April 10, 2016 Accepted: June 13, 2016 Published: June 23, 2016

Abstract

The outcome for T-cell acute lymphoblastic leukemia (T-ALL) in relapse after hematopoietic stem cell transplantation (HSCT) is quite poor, while, both donor lymphocytes infusion (DLI) and adoptively infusion of γδ T cells in leukemia patients after HSCT have demonstrated good results in prolonging survival time of patients. Here, we reported a T-ALL case who experienced three relapses and received HSCT and DLI with an overall survival (OS) time lasting for more than seven years. Based on our previous identification of a leukemic and reactive clone in this patient, continual γδ T cell repertoire monitoring affirmed that the same Vδ5 leukemic clone existed in most samples from the patient, particularly including a sample taken at the time of the third T-ALL relapse, while it could not be detected in the donor sample. In addition, an identical Vδ4 monoclonal T cell that proliferated in the recipient for several years was confirmed to come from the donor graft, and its expression level significantly increased in third leukemia recurrence. These results indicate that clonally expanded Vδ4 T cells may represent a reconstituted γδ T cell repertoire after HSCT, which also hints to a relatively better outcome for this case. Based on this case study, we recommend DLI should be as a treatment strategy for patients who achieve CR or relapse from HSCT. Moreover, dynamically monitoring the TCR repertoire in patients who receive HSCT will benefit in supervising of malignant clone evolution and residue, identifying T cell clones mediate anti-infection, GvHD or GvL.


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