Swati Naik, Subodh Selukar, Aimee C Talleur, Samira Deshpande, Gabriela Llaurador Caraballo, Vanessa A Fabrizio, Rayne H Rouce, Xiaopei Lily Zeng, Anant Vatsayan, Jenna Rossoff, Holly L Pacenta, Samuel John, Christine L Phillips, Julie-An M Talano, Amy Moskop, Michael R Verneris, Gary Douglas Myers, Erin M Hall, Nicole A Karras, Challice L Bonifant, Muna Qayed, Emily Bakinowski, Amy Keating, Susanne H C Baumeister, Emily Tomilson, Michelle L Hermiston, Prakash Satwani, Christa Krupski, Vasant Chinnabhandar, Heather E Stefanski, Emily Egeler, Kevin J Curran, Theodore W Laetsch, Crystal L Mackall, Snehit Prabhu, Khanh Nguyen, Christina Baggott, Liora M Schultz, Kevin O McNerney
{"title":"接受细胞tisagenlecucell治疗的儿科患者血液毒性的表征和预测。","authors":"Swati Naik, Subodh Selukar, Aimee C Talleur, Samira Deshpande, Gabriela Llaurador Caraballo, Vanessa A Fabrizio, Rayne H Rouce, Xiaopei Lily Zeng, Anant Vatsayan, Jenna Rossoff, Holly L Pacenta, Samuel John, Christine L Phillips, Julie-An M Talano, Amy Moskop, Michael R Verneris, Gary Douglas Myers, Erin M Hall, Nicole A Karras, Challice L Bonifant, Muna Qayed, Emily Bakinowski, Amy Keating, Susanne H C Baumeister, Emily Tomilson, Michelle L Hermiston, Prakash Satwani, Christa Krupski, Vasant Chinnabhandar, Heather E Stefanski, Emily Egeler, Kevin J Curran, Theodore W Laetsch, Crystal L Mackall, Snehit Prabhu, Khanh Nguyen, Christina Baggott, Liora M Schultz, Kevin O McNerney","doi":"10.1182/bloodadvances.2025016824","DOIUrl":null,"url":null,"abstract":"<p><p>Hematotoxicity is the most frequent severe toxicity following chimeric antigen receptor (CAR) T therapy. However, limited data exist on risk factors and outcomes for hematotoxicity for children and young adults (CAYA) with B-acute lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel. We conducted a multi-institutional study involving 326 CAYA, with 144 evaluable in an initial training cohort and 141 evaluable in a validation cohort, through the Pediatric Real World CAR Consortium to characterize the incidence and outcomes of prolonged severe neutropenia (PSN) and to develop a predictive risk score for PSN, tailored for use in this population. The incidence of PSN, defined as an absolute neutrophil count (ANC) of <500 cells/µL for ≥ 30 days, was 15.3% in the initial training cohort and 21% in the validation cohort. Development of PSN was associated with inferior overall survival (p<0.001), relapse-free survival (p=0.01), higher non-relapse mortality (p=0.003), and a greater risk of infections within 30 days (p=0.03). Multivariable penalized regression analysis identified key risk factors for PSN which included pre-infusion C-reactive protein and bone marrow disease burden, and post-infusion peak ferritin and occurrence of severe CRS, which were used to create the CytoRisk score. In the validation cohort, the CytoRisk score discriminated between patients with and without PSN (area under the curve: 0.90, specificity: 93%, sensitivity: 71%, positive predictive value: 74%, negative predictive value: 92%). The CytoRisk score may be used to a priori identify patients at highest risk of PSN and overall worse outcomes.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.1000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Characterization and prediction of hematotoxicity in pediatric patients receiving tisagenlecuecel.\",\"authors\":\"Swati Naik, Subodh Selukar, Aimee C Talleur, Samira Deshpande, Gabriela Llaurador Caraballo, Vanessa A Fabrizio, Rayne H Rouce, Xiaopei Lily Zeng, Anant Vatsayan, Jenna Rossoff, Holly L Pacenta, Samuel John, Christine L Phillips, Julie-An M Talano, Amy Moskop, Michael R Verneris, Gary Douglas Myers, Erin M Hall, Nicole A Karras, Challice L Bonifant, Muna Qayed, Emily Bakinowski, Amy Keating, Susanne H C Baumeister, Emily Tomilson, Michelle L Hermiston, Prakash Satwani, Christa Krupski, Vasant Chinnabhandar, Heather E Stefanski, Emily Egeler, Kevin J Curran, Theodore W Laetsch, Crystal L Mackall, Snehit Prabhu, Khanh Nguyen, Christina Baggott, Liora M Schultz, Kevin O McNerney\",\"doi\":\"10.1182/bloodadvances.2025016824\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Hematotoxicity is the most frequent severe toxicity following chimeric antigen receptor (CAR) T therapy. However, limited data exist on risk factors and outcomes for hematotoxicity for children and young adults (CAYA) with B-acute lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel. We conducted a multi-institutional study involving 326 CAYA, with 144 evaluable in an initial training cohort and 141 evaluable in a validation cohort, through the Pediatric Real World CAR Consortium to characterize the incidence and outcomes of prolonged severe neutropenia (PSN) and to develop a predictive risk score for PSN, tailored for use in this population. The incidence of PSN, defined as an absolute neutrophil count (ANC) of <500 cells/µL for ≥ 30 days, was 15.3% in the initial training cohort and 21% in the validation cohort. Development of PSN was associated with inferior overall survival (p<0.001), relapse-free survival (p=0.01), higher non-relapse mortality (p=0.003), and a greater risk of infections within 30 days (p=0.03). Multivariable penalized regression analysis identified key risk factors for PSN which included pre-infusion C-reactive protein and bone marrow disease burden, and post-infusion peak ferritin and occurrence of severe CRS, which were used to create the CytoRisk score. In the validation cohort, the CytoRisk score discriminated between patients with and without PSN (area under the curve: 0.90, specificity: 93%, sensitivity: 71%, positive predictive value: 74%, negative predictive value: 92%). 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Characterization and prediction of hematotoxicity in pediatric patients receiving tisagenlecuecel.
Hematotoxicity is the most frequent severe toxicity following chimeric antigen receptor (CAR) T therapy. However, limited data exist on risk factors and outcomes for hematotoxicity for children and young adults (CAYA) with B-acute lymphoblastic leukemia (B-ALL) treated with tisagenlecleucel. We conducted a multi-institutional study involving 326 CAYA, with 144 evaluable in an initial training cohort and 141 evaluable in a validation cohort, through the Pediatric Real World CAR Consortium to characterize the incidence and outcomes of prolonged severe neutropenia (PSN) and to develop a predictive risk score for PSN, tailored for use in this population. The incidence of PSN, defined as an absolute neutrophil count (ANC) of <500 cells/µL for ≥ 30 days, was 15.3% in the initial training cohort and 21% in the validation cohort. Development of PSN was associated with inferior overall survival (p<0.001), relapse-free survival (p=0.01), higher non-relapse mortality (p=0.003), and a greater risk of infections within 30 days (p=0.03). Multivariable penalized regression analysis identified key risk factors for PSN which included pre-infusion C-reactive protein and bone marrow disease burden, and post-infusion peak ferritin and occurrence of severe CRS, which were used to create the CytoRisk score. In the validation cohort, the CytoRisk score discriminated between patients with and without PSN (area under the curve: 0.90, specificity: 93%, sensitivity: 71%, positive predictive value: 74%, negative predictive value: 92%). The CytoRisk score may be used to a priori identify patients at highest risk of PSN and overall worse outcomes.
期刊介绍:
Blood Advances, a semimonthly medical journal published by the American Society of Hematology, marks the first addition to the Blood family in 70 years. This peer-reviewed, online-only, open-access journal was launched under the leadership of founding editor-in-chief Robert Negrin, MD, from Stanford University Medical Center in Stanford, CA, with its inaugural issue released on November 29, 2016.
Blood Advances serves as an international platform for original articles detailing basic laboratory, translational, and clinical investigations in hematology. The journal comprehensively covers all aspects of hematology, including disorders of leukocytes (both benign and malignant), erythrocytes, platelets, hemostatic mechanisms, vascular biology, immunology, and hematologic oncology. Each article undergoes a rigorous peer-review process, with selection based on the originality of the findings, the high quality of the work presented, and the clarity of the presentation.