Publications by authors named "Furun An"

3 Publications

  • Page 1 of 1

CD4CD25CD127 regulatory T cells associated with the effect of CD19 CAR-T therapy for relapsed/refractory B-cell acute lymphoblastic leukemia.

Int Immunopharmacol 2021 May 11;96:107742. Epub 2021 May 11.

Hematology Department, the Second Hospital of Anhui Medical University (SHAMU), Hefei, Anhui Province, China; Hematologic Diseases Research Center of Anhui Medical University, Hefei, Anhui Province, China. Electronic address:

Background: CD19-specific chimeric antigen receptor T-cell (CAR-T) therapy has shown promising clinical outcomes in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) patients. However, some patients did not respond to this therapy or relapsed after remission. Regulatory T cells (Tregs) have shown great importance in promoting tumor escape, but little is known about their role in R/R B-ALL patients with CAR-T therapy. Our previous study has proved that higher Tregs before infusion was an independent high-risk factor for relapse-free survival (RFS). To further clarify the relationship between Tregs and the efficacy of CAR-T therapy, the present study tested the levels of CD4CD25CD127 Tregs in peripheral blood (PB) of R/R B-ALL patients at different stages of CD19 CAR-T therapy, and evaluate their impact on the efficacy and prognosis of CAR-T therapy.

Methods: From November 2015 to May 2019, 47 R/R B-ALL patients successfully received CD19 CAR-T therapy at our institution and followed up for at least 1 month. Among them, one patient did not tested for Tregs, so 46 patients enrolled in this study. We collected clinical information of them and dynamically detected the frequency of CD4CD25CD127 Tregs within CD4 + T cells at different time points (before infusion and at 1 week after infusion) by flow cytometry, and validated the relationship of circulating Tregs with clinical efficacy, OS, and recurrence of CAR-T therapy.

Results: Circulating Tregs of R/R B-ALL patients in pre-infusion group (median 6.67%) and in 1 week after infusion group (median 6.80%) were all higher than that of the healthy control group (median 5.04%), with statistical significance (P < 0.05). The frequencies of Tregs in not remission (NR) group at baseline (pre-infusion) and at 1 week after infusion were all significantly higher than those in remission group. With cut-off values of 11.54% (before infusion) and 13.56% (1 week after infusion), the specificity for Tregs were 94.6% and 100% , respectively. In remission group, 11 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving remission by Sino 19 cell therapy. No significant differences of Tregs expression were found between transplantation and non-transplantation groups. Time-dependent Cox model showed that transplantation group had lower risk of relapse and death when compared with non-transplantation group (HR = 0.664 for RFS and HR = 0.364 for OS), however, no statistical significances were found (P = 0.403 and 0.106, respectively). Higher Tregs before infusion and at 1 week after infusion were significant associated with shorter RFS and OS by Kaplan-Meier analysis. Multivariate analysis showed that higher Tregs at 1 week after infusion was the independently factor for poor RFS (P = 0.032) and shorter OS (P = 0.025) in R/R B-ALL patients with CD19 CAR-T therapy. Besides, Tregs levels before and at 1 week after infusion were negatively correlated with the persistence time of Sino 19 cell.

Conclusion: Higher circulating Tregs, especially 1 week after CD19 CAR-T cell infusion, was a poor predict indicator for CD19 CAR-T therapy in R/R B-ALL patients.
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http://dx.doi.org/10.1016/j.intimp.2021.107742DOI Listing
May 2021

Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia.

Nat Commun 2020 11 23;11(1):5928. Epub 2020 Nov 23.

Hematology Department, the Second Hospital of Anhui Medical University (SHAMU), Hefei, Anhui Province, China.

CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.
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http://dx.doi.org/10.1038/s41467-020-19774-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683530PMC
November 2020

Hepatosplenic T-Cell Lymphoma in an Immunocompetent Male with Central Nervous System Invasion: A Rare Clinical Entity.

Cytometry B Clin Cytom 2019 11 30;96(6):475-479. Epub 2018 Nov 30.

Department of Hematology, Hamatological Research Center, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China.

Hepatosplenic T-cell lymphoma (HSTCL) is a very rare non-Hodgkin lymphoma with an aggressive clinical course and poor prognosis. Patients of this disease usually presented with hepatosplenomegaly, which can be misdiagnosed or delayed. Bone marrow (BM) and peripheral blood (PB) are frequently involved, however, central nervous system (CNS) involvement is less common. Here, we are reporting an unusual case of hepatosplenic γδ T-cell lymphoma in a 64-year-old man with CNS involvement. Flow cytometry immunophenotyping was proved of great diagnostic contribution. © 2018 International Clinical Cytometry Society.
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http://dx.doi.org/10.1002/cyto.b.21736DOI Listing
November 2019