Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acut
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CASE REPORT
Open Access
Secondary donor-derived humanized CD19modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report Meng-Yun Li1†, Zhi-Hong Lin2†, Ming-Ming Hu2†, Li-Qing Kang3,4†, Xiao-xia Wu1, Qi-wei Chen1, Xin Kong1, Jian Zhang1* , Hui-Ying Qiu1* and De-Pei Wu1
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. Keywords: CD19, Chimeric antigen receptor T cells, Donor-derived, Humanized, Mixed phenotype acute leukemia
* Correspondence: [email protected]; [email protected] † Meng-Yun Li, Zhi-Hong Lin, Ming-Ming Hu and Li-Qing Kang are co-first authors. 1 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, 188 Shizi Street, Suzhou 215006, P.R. China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to
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