scholarly journals CNS relapse of B-lymphoblastic lymphoma after allogeneic hematopoietic stem cell transplantation: therapy with donor CD19-specific CAR-T cells

2021 ◽  
Vol 20 (2) ◽  
pp. 143-147
Author(s):  
O. O. Molostova ◽  
L. N. Shelikhova ◽  
D. E. Pershin ◽  
A. M. Popov ◽  
M. E. Dubrovina ◽  
...  

Presently, there is no consensus on the best treatment for relapsed B-cell acute lymphoblastic leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in patients with extramedullary lesions. There are certain anti-tumor drugs that can be used in case of relapse after allo-HSCT, however, prospective randomized studies directly comparing different chemotherapy and immunotherapy approaches are generally lacking. Retrospective studies exploring therapy for relapsed disease are difficult to compare due to the inhomogeneity of patient populations and the diversity of treatment approaches. In such situations, the treatment choice is influenced by the characteristics of the tumor population, particularly, its immunophenotype, available drugs, and the experience of a healthcare facility and physicians. This clinical case report describes the process of treating a patient with B-lymphoblastic lymphoma and shows the possibility of using donor CD19-specific CAR-T cells as a treatment for isolated CNS relapse after allo-HSCT. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

Blood ◽  
2013 ◽  
Vol 122 (25) ◽  
pp. 4129-4139 ◽  
Author(s):  
James N. Kochenderfer ◽  
Mark E. Dudley ◽  
Robert O. Carpenter ◽  
Sadik H. Kassim ◽  
Jeremy J. Rose ◽  
...  

Key Points Donor-derived anti-CD19-CAR T cells cause regressions of refractory malignancies after allogeneic transplantation.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4561-4561
Author(s):  
Cheng Zhang ◽  
Lei Gao ◽  
Yao Liu ◽  
Li Gao ◽  
Pei-Yan Kong ◽  
...  

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.


Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4664
Author(s):  
Ariadna Bartoló-Ibars ◽  
Mireia Uribe-Herranz ◽  
Guillermo Muñoz-Sánchez ◽  
Cristina Arnaldos-Pérez ◽  
Valentín Ortiz-Maldonado ◽  
...  

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the standard treatments for B-cell lymphoproliferative disorders; however, deep relapses are common after an allo-HSCT, and it is associated with poor prognosis. A successful approach to overcome these relapses is to exploit the body’s own immune system with chimeric antigen receptor (CAR) T-cells. These two approaches are potentially combinatorial for treating R/R B-cell lymphoproliferative disorders. Several clinical trials have described different scenarios in which allo-HSCT and CAR-T are successively combined. Further, for all transplanted patients, assessment of chimerism is important to evaluate the engraftment success. Nonetheless, for those patients who previously received an allo-HSCT there is no monitorization of chimerism before manufacturing CAR T-cells. In this review, we focus on allo-HSCT and CAR-T treatments and the different sources of T-cells for manufacturing CAR T-cells.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5225-5225
Author(s):  
Jun Liu ◽  
Xu Tan ◽  
Ma Ying-Ying ◽  
Wang Mai-Hong ◽  
Yao Liu ◽  
...  

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.


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