{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:47:27Z","timestamp":1793850447490,"version":"4.6.1"},"reference-count":55,"publisher":"American Society of Hematology","issue":"14","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chimeric antigen receptor (CAR) T-cell therapy can induce durable remissions of relapsed\/refractory B-acute lymphoblastic leukemia (ALL). However, case reports suggested differential outcomes mediated by leukemia cytogenetics. We identified children and young adults with relapsed\/refractory CD19+ ALL\/lymphoblastic lymphoma treated on 5 CD19-directed CAR T-cell (CTL019 or humanized CART19) clinical trials or with commercial tisagenlecleucel from April 2012 to April 2019. Patients were hierarchically categorized according to leukemia cytogenetics: High-risk lesions were defined as KMT2A (MLL) rearrangements, Philadelphia chromosome (Ph+), Ph-like, hypodiploidy, or TCF3\/HLF; favorable as hyperdiploidy or ETV6\/RUNX1; and intermediate as iAMP21, IKZF1 deletion, or TCF3\/PBX1. Of 231 patients aged 1 to 29, 74 (32%) were categorized as high risk, 28 (12%) as intermediate, 43 (19%) as favorable, and 86 (37%) as uninformative. Overall complete remission rate was 94%, with no difference between strata. There was no difference in relapse-free survival (RFS; P = .8112), with 2-year RFS for the high-risk group of 63% (95% confidence interval [CI], 52-77). There was similarly no difference seen in overall survival (OS) (P = .5488), with 2-year OS for the high-risk group of 70% (95% CI, 60-82). For patients with KMT2A-rearranged infant ALL (n = 13), 2-year RFS was 67% (95% CI, 45-99), and OS was 62% (95% CI, 40-95), with multivariable analysis demonstrating no increased risk of relapse (hazard ratio, 0.70; 95% CI, 0.21-2.90; P\u00a0= .7040) but a higher proportion of relapses associated with myeloid lineage switch and a 3.6-fold increased risk of all-cause death (95% CI, 1.04-12.75; P = .0434). CTL019\/huCART19\/tisagenlecleucel are effective at achieving durable remissions across cytogenetic categories. Relapsed\/refractory patients with high-risk cytogenetics, including KMT2A-rearranged infant ALL, demonstrated high RFS and OS probabilities at 2 years.<\/jats:p>","DOI":"10.1182\/blood.2021012727","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T16:56:20Z","timestamp":1638809780000},"page":"2173-2185","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":108,"title":["Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR\u00a0T-cell therapy"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-4064","authenticated-orcid":false,"given":"Allison Barz","family":"Leahy","sequence":"first","affiliation":[{"name":"Division of Oncology and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Penn Center for Cancer Care Innovation, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA;"},{"name":"Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin J.","family":"Devine","sequence":"additional","affiliation":[{"name":"Division of Oncology and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2542-2061","authenticated-orcid":false,"given":"Regina","family":"Myers","sequence":"additional","affiliation":[{"name":"Division of Oncology and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"DiNofia","sequence":"additional","affiliation":[{"name":"Division of Oncology and Cancer Immunotherapy Program, 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Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Callahan","sequence":"additional","affiliation":[{"name":"Division of Oncology and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Baniewicz","sequence":"additional","affiliation":[{"name":"Division of Oncology and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Patino","sequence":"additional","affiliation":[{"name":"Division of Oncology and Cancer 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PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan A.","family":"Grupp","sequence":"additional","affiliation":[{"name":"Division of Oncology and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Division of Oncology and Cancer Immunotherapy Program, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"},{"name":"Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Philadelphia, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon L.","family":"Maude","sequence":"additional","affiliation":[{"name":"Division of 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