MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation
EP300-ZNF384-positive B cell acute lymphoblastic leukemia (B-ALL) patients are reported to have a unique immunophenotype with high expression of CD19 and CD22, weak expression of CD20 and aberrant expression of CD13 and/or CD33, sensitivity to chemotherapy and a favorable outcome. To date, the cases...
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| Veröffentlicht in: | OncoTargets and therapy 2021-10, Vol.14, p.5197-5204 |
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| creator | Zhang, Xin-Yue Dai, Hai-Ping Zhang, Ling Liu, Si-Ning Dai, Yin Wu, De-Pei Tang, Xiao-Wen |
| description | EP300-ZNF384-positive B cell acute lymphoblastic leukemia (B-ALL) patients are reported to have a unique immunophenotype with high expression of CD19 and CD22, weak expression of CD20 and aberrant expression of CD13 and/or CD33, sensitivity to chemotherapy and a favorable outcome. To date, the cases of only 53 patients have been reported, albeit few reports on salvage therapy when conventional chemotherapies failed. Here, we describe two relapsed and refractory adult B-ALL patients with EP300-ZNF384 who achieved second remission through tandem CD19/CD22 CAR T-cell therapy. Grade 3 and 2 cytokine release syndrome were observed in cases 1 and 2, respectively. No immune effector cell-associated neurotoxicity syndrome was detected. Both patients underwent consolidate haploidentical hematopoietic stem cell transplantation (HSCT), and each maintained measurable residual disease-negative remission for 14 and 13 months, respectively. Our study suggests that CD19/CD22 CAR T-cell therapy bridging to allogeneic HSCT may be a viable option for EP300-ZNF384-positive B-ALL. Keywords: chimeric antigen receptor T-cells, CD19/CD22, EP300-ZNF384, acute lymphoblastic leukemia, relapsed/refractory |
| doi_str_mv | 10.2147/OTT.S324765 |
| format | Article |
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To date, the cases of only 53 patients have been reported, albeit few reports on salvage therapy when conventional chemotherapies failed. Here, we describe two relapsed and refractory adult B-ALL patients with EP300-ZNF384 who achieved second remission through tandem CD19/CD22 CAR T-cell therapy. Grade 3 and 2 cytokine release syndrome were observed in cases 1 and 2, respectively. No immune effector cell-associated neurotoxicity syndrome was detected. Both patients underwent consolidate haploidentical hematopoietic stem cell transplantation (HSCT), and each maintained measurable residual disease-negative remission for 14 and 13 months, respectively. Our study suggests that CD19/CD22 CAR T-cell therapy bridging to allogeneic HSCT may be a viable option for EP300-ZNF384-positive B-ALL. Keywords: chimeric antigen receptor T-cells, CD19/CD22, EP300-ZNF384, acute lymphoblastic leukemia, relapsed/refractory</description><identifier>ISSN: 1178-6930</identifier><identifier>EISSN: 1178-6930</identifier><identifier>DOI: 10.2147/OTT.S324765</identifier><identifier>PMID: 34744437</identifier><language>eng</language><publisher>Macclesfield: Dove Medical Press Limited</publisher><subject>Acute lymphoblastic leukemia ; Bone marrow ; Cancer ; Case Series ; CD13 antigen ; CD19 antigen ; CD20 antigen ; CD22 antigen ; Cell therapy ; Chemotherapy ; Cytokines ; Fever ; Flow cytometry ; Genes ; Graft versus host disease ; Hematopoietic stem cells ; Hypotension ; Leukemia ; Lymphatic leukemia ; Lymphocytes T ; Monoclonal antibodies ; Mutation ; Neurotoxicity ; Patients ; Remission ; Remission (Medicine) ; Stem cell transplantation ; Stem cells ; T cells ; Transplantation ; Vincristine ; Young adults</subject><ispartof>OncoTargets and therapy, 2021-10, Vol.14, p.5197-5204</ispartof><rights>COPYRIGHT 2021 Dove Medical Press Limited</rights><rights>2021. This work is licensed under https://creativecommons.org/licenses/by-nc/3.0/ (the “License”). 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To date, the cases of only 53 patients have been reported, albeit few reports on salvage therapy when conventional chemotherapies failed. Here, we describe two relapsed and refractory adult B-ALL patients with EP300-ZNF384 who achieved second remission through tandem CD19/CD22 CAR T-cell therapy. Grade 3 and 2 cytokine release syndrome were observed in cases 1 and 2, respectively. No immune effector cell-associated neurotoxicity syndrome was detected. Both patients underwent consolidate haploidentical hematopoietic stem cell transplantation (HSCT), and each maintained measurable residual disease-negative remission for 14 and 13 months, respectively. Our study suggests that CD19/CD22 CAR T-cell therapy bridging to allogeneic HSCT may be a viable option for EP300-ZNF384-positive B-ALL. Keywords: chimeric antigen receptor T-cells, CD19/CD22, EP300-ZNF384, acute lymphoblastic leukemia, relapsed/refractory</description><subject>Acute lymphoblastic leukemia</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Case Series</subject><subject>CD13 antigen</subject><subject>CD19 antigen</subject><subject>CD20 antigen</subject><subject>CD22 antigen</subject><subject>Cell therapy</subject><subject>Chemotherapy</subject><subject>Cytokines</subject><subject>Fever</subject><subject>Flow cytometry</subject><subject>Genes</subject><subject>Graft versus host disease</subject><subject>Hematopoietic stem cells</subject><subject>Hypotension</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Lymphocytes T</subject><subject>Monoclonal antibodies</subject><subject>Mutation</subject><subject>Neurotoxicity</subject><subject>Patients</subject><subject>Remission</subject><subject>Remission (Medicine)</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>T cells</subject><subject>Transplantation</subject><subject>Vincristine</subject><subject>Young adults</subject><issn>1178-6930</issn><issn>1178-6930</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptktFq2zAUhs3YWLtuV3sBwWA3w6lsSbZ8M3CdditkbUi9m90IWT52VBQptexCXmbPOqUNWwNDFxLS9_-c8-tE0ccEz9KE5ue3dT27IynNM_YqOk2SnMdZQfDrF-eT6J339xhnGU_p2-iE0JxSSvLT6PeP1Ty-gV6O-hHQCjbae-0surbtpKBF2qLLJcE4_nVzRThFS-f1E3oRl4sFWgYd2NGjZodqaVvYoGqeFOfVPE1RVa5QHVdgDKrXMMjtDl0Muu217dHoUGmM68GCVuhu3AufwEFavzXSjsHZ2ffRm04aDx8O-1n08-qyrr7Hi9tv11W5iBVlyRgXwNqGSAU86TpMOkYKyLDiShYNZWnCOWaQNW0OvFPQtTjnbZE3mDCGcdFJchZ9ffbdTs0GWhV6GqQR20Fv5LATTmpx_GL1WvTuUXCWsYLTYPDpYDC4hwn8KO7dNNhQs0gDkGCSU_yP6qUBoW3ngpkKmStRhq9hOCc8DdTsP1RYIV6tnIVOh_sjwecXgjVIM669M9M-QX8MfnkG1eC8H6D722GCxX6YRBgmcRgm8genXreX</recordid><startdate>20211031</startdate><enddate>20211031</enddate><creator>Zhang, Xin-Yue</creator><creator>Dai, Hai-Ping</creator><creator>Zhang, Ling</creator><creator>Liu, Si-Ning</creator><creator>Dai, Yin</creator><creator>Wu, De-Pei</creator><creator>Tang, Xiao-Wen</creator><general>Dove Medical Press Limited</general><general>Taylor & Francis Ltd</general><general>Dove</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1125-7744</orcidid><orcidid>https://orcid.org/0000-0002-2100-0152</orcidid></search><sort><creationdate>20211031</creationdate><title>MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation</title><author>Zhang, Xin-Yue ; Dai, Hai-Ping ; Zhang, Ling ; Liu, Si-Ning ; Dai, Yin ; Wu, De-Pei ; Tang, Xiao-Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-9e5db3ace81ff03f539e60c8ca9b45218805e6bd7e8fcefd078d97b0355009fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Bone marrow</topic><topic>Cancer</topic><topic>Case Series</topic><topic>CD13 antigen</topic><topic>CD19 antigen</topic><topic>CD20 antigen</topic><topic>CD22 antigen</topic><topic>Cell therapy</topic><topic>Chemotherapy</topic><topic>Cytokines</topic><topic>Fever</topic><topic>Flow cytometry</topic><topic>Genes</topic><topic>Graft versus host disease</topic><topic>Hematopoietic stem cells</topic><topic>Hypotension</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Lymphocytes T</topic><topic>Monoclonal antibodies</topic><topic>Mutation</topic><topic>Neurotoxicity</topic><topic>Patients</topic><topic>Remission</topic><topic>Remission (Medicine)</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>T cells</topic><topic>Transplantation</topic><topic>Vincristine</topic><topic>Young adults</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Xin-Yue</creatorcontrib><creatorcontrib>Dai, Hai-Ping</creatorcontrib><creatorcontrib>Zhang, Ling</creatorcontrib><creatorcontrib>Liu, Si-Ning</creatorcontrib><creatorcontrib>Dai, Yin</creatorcontrib><creatorcontrib>Wu, De-Pei</creatorcontrib><creatorcontrib>Tang, Xiao-Wen</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>OncoTargets and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xin-Yue</au><au>Dai, Hai-Ping</au><au>Zhang, Ling</au><au>Liu, Si-Ning</au><au>Dai, Yin</au><au>Wu, De-Pei</au><au>Tang, Xiao-Wen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation</atitle><jtitle>OncoTargets and therapy</jtitle><date>2021-10-31</date><risdate>2021</risdate><volume>14</volume><spage>5197</spage><epage>5204</epage><pages>5197-5204</pages><issn>1178-6930</issn><eissn>1178-6930</eissn><abstract>EP300-ZNF384-positive B cell acute lymphoblastic leukemia (B-ALL) patients are reported to have a unique immunophenotype with high expression of CD19 and CD22, weak expression of CD20 and aberrant expression of CD13 and/or CD33, sensitivity to chemotherapy and a favorable outcome. To date, the cases of only 53 patients have been reported, albeit few reports on salvage therapy when conventional chemotherapies failed. Here, we describe two relapsed and refractory adult B-ALL patients with EP300-ZNF384 who achieved second remission through tandem CD19/CD22 CAR T-cell therapy. Grade 3 and 2 cytokine release syndrome were observed in cases 1 and 2, respectively. No immune effector cell-associated neurotoxicity syndrome was detected. Both patients underwent consolidate haploidentical hematopoietic stem cell transplantation (HSCT), and each maintained measurable residual disease-negative remission for 14 and 13 months, respectively. Our study suggests that CD19/CD22 CAR T-cell therapy bridging to allogeneic HSCT may be a viable option for EP300-ZNF384-positive B-ALL. Keywords: chimeric antigen receptor T-cells, CD19/CD22, EP300-ZNF384, acute lymphoblastic leukemia, relapsed/refractory</abstract><cop>Macclesfield</cop><pub>Dove Medical Press Limited</pub><pmid>34744437</pmid><doi>10.2147/OTT.S324765</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1125-7744</orcidid><orcidid>https://orcid.org/0000-0002-2100-0152</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acute lymphoblastic leukemia Bone marrow Cancer Case Series CD13 antigen CD19 antigen CD20 antigen CD22 antigen Cell therapy Chemotherapy Cytokines Fever Flow cytometry Genes Graft versus host disease Hematopoietic stem cells Hypotension Leukemia Lymphatic leukemia Lymphocytes T Monoclonal antibodies Mutation Neurotoxicity Patients Remission Remission (Medicine) Stem cell transplantation Stem cells T cells Transplantation Vincristine Young adults |
| title | MRD-Negative Remission Induced in EP300-ZNF384 Positive B-ALL Patients by Tandem CD19/CD22 CAR T-Cell Therapy Bridging to Allogeneic Stem Cell Transplantation |
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