{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:27:21Z","timestamp":1786688841039,"version":"build-2736575974"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LKLY25H160010"],"award-info":[{"award-number":["LKLY25H160010"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2025HY1372"],"award-info":[{"award-number":["2025HY1372"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008092","name":"Jinhua Science and Technology Bureau","doi-asserted-by":"publisher","award":["2024-4-237"],"award-info":[{"award-number":["2024-4-237"]}],"id":[{"id":"10.13039\/501100008092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Therapy-related myeloid neoplasms (t-MNs) have emerged as a serious late complication of CD19-directed chimeric antigen receptor (CAR) T-cell therapy. While large-scale studies have characterized the epidemiology of t-MNs, the mechanisms underlying their development remain incompletely understood, and cases with extended latency are rarely documented. We report a case of therapy-related acute myeloid leukemia (t-AML) occurring 24 months after initial CD19 CAR-T cell therapy, with longitudinal genomic monitoring demonstrating evolution from wild-type TP53 to biallelic TP53 loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 65-year-old male was diagnosed with germinal center B-cell (GCB)-type diffuse large B-cell lymphoma (DLBCL) in February 2019. After first-line R-CHOP chemotherapy and subsequent relapse, he received two courses of CD19 CAR-T cell therapy (June 2020 and February 2021) with sintilimab maintenance. Twenty-four months after the first CAR-T infusion, he presented with pancytopenia. Bone marrow examination revealed increased primitive and immature mononuclear cells, with flow cytometry confirming 9.49% abnormal myeloid blasts (CD34+, CD117+, MPO+) consistent with AML-M5b. Cytogenetic analysis demonstrated a complex karyotype: 44-45, XY, del(5)(q14q33),\u221216, der(17;18)(q10;q10),-19, add(21q). Next-generation sequencing identified biallelic TP53 loss (copy number loss and p.P278A point mutation in exon 8). Notably, NGS at initial DLBCL diagnosis had shown wild-type TP53. The patient received azacitidine plus venetoclax, achieving partial remission, followed by child-to-parent haploidentical allogeneic hematopoietic stem cell transplantation. DLBCL remained in remission throughout AML-directed therapy. The patient ultimately died from COVID-19 pneumonia in December 2022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case illustrates a rare but serious late complication of CD19 CAR-T cell therapy, characterized by an exceptionally long 24-month latency and documented evolution from wild-type TP53 to biallelic loss. While causality cannot be established from a single case, these findings are consistent with the hypothesis that prolonged genotoxic stress and inflammatory cytokine exposure may promote clonal selection of TP53-mutated hematopoietic cells. This report underscores the necessity of extended hematologic surveillance beyond the first 12 months post-CAR-T infusion, baseline CHIP screening prior to therapy, and systematic longitudinal genomic profiling in future cases to validate these observations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1876141","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:33:37Z","timestamp":1786685617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapy-related acute myeloid leukemia with 24-month latency after CD19 CAR-T cell therapy in relapsed\/refractory diffuse large B-cell lymphoma: a case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Manqi","family":"Su","sequence":"first","affiliation":[{"name":"Department of Hematology, Dongyang People's Hospital, Dongyang Hospital Affiliated to WenZhou Medical University","place":["Dongyang, 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