Donor-derived CAR-T Cells Serve as a Reduced-intensity Conditioning Regimen for Haploidentical Stem Cell Transplantation in Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: Case Report and Review of the Literature.

Abstract

BACKGROUND:

Reduced-intensity conditioning (RIC) regimens with low tolerable toxicities have been used for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relapse rate by this treatment is high. Treatment of CD19 B-cell relapsed/refractory acute lymphoblastic leukemia (r/r ALL) with allogeneic chimeric antigen receptor-modified T (CAR-T) cells is safe and effective. Use of allogeneic CD19-CAR-T cells as a part of RIC regimens for treatment of r/r ALL patients with haploidentical HSCT has not been investigated yet.

CASE PRESENTATION:

A 12-year-old girl with CD19 r/r ALL underwent haploidentical HSCT. The patient received fludarabine, busulfan, and cyclophosphamide combined with haploidentical donor-derived CD19-CAR-T cells as the conditioning regimen. Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells and granulocyte colony-stimulating factor-mobilized bone marrow were infused on days 1 and 2, respectively. Mycophenolate mofetil and tacrolimus were administered on day 1, antithymocyte globulin was administered on days +14 and +15, and a short course of methotrexate was administered to prevent graft-versus-host disease. The time of peak CAR-T cell proliferation was detected after the first infusion of CAR-T cells on day 7. The patient's engraftment and full-donor cell engraftment were established. The disease was in complete remission with minimal residual disease, which was undetectable by flow cytometry. No graft-versus-host disease or serious cytokine-release syndrome was found.

CONCLUSIONS:

Treatment of r/r ALL with RIC including CD19-CAR-T cells followed by allo-HSCT was safe and effective, which suggest that CAR-T cells can be used as a part of RIC regimens in the treatment of r/r ALL in haploidentical HSCT.

• Authors: Cheng Zhang, Pei-Yan Kong, Shiqi Li, Ting Chen, Xun Ni, Yunyan Li, Meiling Wang, Yao Liu, Lei Gao, Li Gao, Xian-Gui Peng, Ai-Hua Sun, Ping Wang, Zhi Yang, Xi Zhang, Cheng Qian
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) 2018 Jul/Aug Vol. 41 Issue 6 Pg. 306-311 ISSN: 1537-4513 [Electronic] United States
• PMID: 29864079 (Publication Type: Case Reports, Journal Article, Review)

Chemical References

• Antigens, CD19

Topics

• Antigens, CD19 (metabolism)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cell Proliferation
• Child
• Drug Resistance, Neoplasm
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunotherapy, Adoptive (methods)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (immunology, therapy)
• Remission Induction
• T-Lymphocytes (physiology, transplantation)
• Transplantation Conditioning
• Transplantation, Haploidentical
• Treatment Outcome