scholarly journals Study on Use of CAR-T Cells in Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5225-5225
Author(s):  
Jun Liu ◽  
Xu Tan ◽  
Ma Ying-Ying ◽  
Wang Mai-Hong ◽  
Yao Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Car T Cells ◽  
Car T

Abstract Background: The chimeric antigen receptor T (CAR-T) cells have showed strong anti-leukemia role, which can treat or prevent relapse by targeting minimal residual disease for patients undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The infusion of allogeneic CAR-T cells may cause the graft-versus-host disease, which could limit its use during and after allo-HSCT. It is still unclear whether CAR-T cells can be used during and after allo-HSCT. In this study, the use of CAR-T cells in these situation was explored. Methods: Two patients with relapsed/refractory acute lymphoblastic leukemia (ALL) received allo-HSCT, the CAR-T cells was used as a reduced-intensity conditioning regimen. Another three patients with high-risk ALL received preventive infusion of CAR-T cells on days +60 after allo-HSCT. Results: For patients undergone allo-HSCT, the time of peak CAR-T cell proliferation was detected after the first infusion of CAR-T cells on day 7. The engraftment and full donor cell engraftment were established. The disease was in complete remission with negative minimal residual disease, which was undetectable by flow cytometry. No graft-versus-host disease and serious cytokine release syndrome was found. For patients received preventive infusion of CAR-T cells, the CAR-T cells continually survival. No graft-versus-host disease and serious cytokine release syndrome was found. The disease is complete remission for 1-6 months. Conclusion: It is safety and effective for CAR-T cells used in allogeneic hematopoietic stem cell transplantation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of Donor-Derived CD19.CAR-T Cells in Treating Patients That Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4561-4561
Author(s):  
Cheng Zhang ◽  
Lei Gao ◽  
Yao Liu ◽  
Li Gao ◽  
Pei-Yan Kong ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Car T

Background The Chimeric Antigen Receptor T (CAR-T) cells with strong anti-leukemia role can treat relapsed/refractory CD19-positive acute lymphoblastic leukemia (CD19+-ALL) with good outcome. The allogeneic CAR-T cells receives activation signals from both T cell receptor (TCR) and CAR, which may possess stronger activity in anti-leukemia cells. However, the infusion of allogeneic CAR-T cells may cause graft-versus-host disease, which could limit its application after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is still unclear that the role of the donor-derived CAR-T cells in treating relapsed patients after allo-HSCT. In this study, the prospective study was performed to investigate the role of donor-derived CAR-T cells on relapsed patients after allo-HSCT. Methods From April 2016 to March 2019, relapsed patients after allo-HSCT with CD19+-ALL and a Karnofsky score greater than or equal to 60 were enrolled in this study. The donor underwent apheresis for mononuclear cells to construct the CAR-T cells. The bone marrow aspiration every month after CART- cells infusion was carried out for the assessment of disease status by follow cytometry. The chimerism was detected every month after CAR-T cells treatment. Results Eighteen patients enrolled in this study. The median number of infused CAR-T cells was 1.825Í106/Kg. Thirteen patients (13/18=72.22%) reached complete remission (CR) after CAR-T cells treatment. Four patients (4/18=22.22%) had ineffectiveness. One patient died from b uncontrolled bleeding because of low platelet. The patients with blast cells <5% had higher CR. The full chimerism achieved after CART- cells treatment for all patients with the decrease of chimerism at the time of relapse. The median time of follow-up was seven months (ranged from three months to twenty-five months). Three patients with decreased CAR-T cells or chimerism was underwent allogeneic hematopoietic stem cell transplantation or relapsed within six months. The other eleven patients were complete remission with full chimerism or the continual proliferation of CAR-T cells without the second allo-HSCT during our follow-up period. Seventeen patients observed cytokine release syndrome in which six patients with degree III-IV. Two patients developed GVHD in skin and intestinal tract. All patients recovered after management. No other severe complications and death were observed. Conclusion Our results showed that the treatment by donor-derived CAR-T cells for relapsed patients after allo-HSCT is safe and effective. No second transplantation was needed for relapsed patients after allo-HSCT with the treatment of donor-derived CAR-T cells that with good chimerism and continual proliferation of CAR-T cells. However, further clinical trials should be performed to investigate this protocol with larger cases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Donor Cell Composition and Reactivity Predict Risk of Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Darius Sairafi ◽  
Arwen Stikvoort ◽  
Jens Gertow ◽  
Jonas Mattsson ◽  
Michael Uhlin
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Background. Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). We designed a functional assay for assessment of individual risk for acute GVHD.Study Design and Methods. Blood samples were collected from patients and donors before HSCT. Two groups of seven patients each were selected, one in which individuals developed acute GVHD grades II–IV and one in which none showed any clinical signs of GVHD. Peripheral blood mononuclear cells (PBMCs) isolated from donors were incubated in mixed lymphocyte cultures (MLCs) with recipient PBMCs. The cells were characterized by flow cytometry before and after MLC.Results. Samples from donors in the GVHD group contained significantly lower frequencies of naïveγδT-cells and T-cells expressing NK-cell markers CD56 and CD94. Donor samples in this group also exhibited lower frequencies of naïve CD95+T-cells compared to controls. After MLC, there were dissimilarities in the CD4/CD8 T-cell ratio and frequency of CD69+T-cells between the two patient groups, with the non-GVHD group showing higher frequencies of CD8+and CD69+T-cells.Conclusion. We conclude that a thorough flow cytometric analysis of donor cells for phenotype and allogeneic reactivity may be of value when assessing pretransplant risk for severe acute GVHD.

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