Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report

Meng-Yun Li; Zhi-Hong Lin; Ming-Ming Hu; Li-Qing Kang; Xiao-xia Wu; Qi-wei Chen; Xin Kong; Jian Zhang; Hui-Ying Qiu; De-Pei Wu

doi:10.1186/s40364-020-00216-1

Biomarker Research (Aug 2020)

Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report

Meng-Yun Li,
Zhi-Hong Lin,
Ming-Ming Hu,
Li-Qing Kang,
Xiao-xia Wu,
Qi-wei Chen,
Xin Kong,
Jian Zhang,
Hui-Ying Qiu,
De-Pei Wu

Affiliations

Meng-Yun Li: Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow University
Zhi-Hong Lin: Suzhou Yongding Hospital
Ming-Ming Hu: Suzhou Yongding Hospital
Li-Qing Kang: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University
Xiao-xia Wu: Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow University
Qi-wei Chen: Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow University
Xin Kong: Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow University
Jian Zhang: Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow University
Hui-Ying Qiu: Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow University
De-Pei Wu: Jiangsu Institute of Hematology, National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Soochow University

DOI: https://doi.org/10.1186/s40364-020-00216-1
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 6

Abstract

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Abstract Background Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. Case presentation We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. Conclusion This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells.

Published in Biomarker Research

ISSN: 2050-7771 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://biomarkerres.biomedcentral.com/

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