{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T02:27:56Z","timestamp":1773714476493,"version":"3.50.1"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Germline Checkpoint Kinase 2 gene (<jats:italic>CHEK2)<\/jats:italic> mutations can increase the risk of solid tumors. Recently, they have been identified as risk factors for hematologic malignancies. However, to the best of our knowledge, B-acute lymphoblastic leukemia (B-ALL) has never been described as a presenting manifestation of germline <jats:italic>CHEK2<\/jats:italic> mutation. Chimeric antigen receptor-T (CAR-T) cell therapy directed against CD19 antigen (tisagenlecleucel) is a novel cellular therapy for treatment of relapsed\/refractory (R\/R) B-ALL. The use of tisagenlecleucel has not been described in patients with <jats:italic>CHEK2<\/jats:italic> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>We describe a case of a pediatric patient with a heterozygous pathogenic germline <jats:italic>CHEK2<\/jats:italic> mutation (c.1100delC; p.Thr367Metfs*15) successfully treated with tisagenlecleucel for relapsed B-ALL to avoid hematopoietic cell transplant (HCT). The twelve-year-old boy was diagnosed with National Cancer Institute (NCI) high-risk B-ALL (white blood cell count &amp;gt;50,000\/mcL), with no extramedullary disease. Cytogenetic analysis revealed normal karyotype but fluorescent <jats:italic>in situ<\/jats:italic> hybridization (FISH) showed 93% positivity for <jats:italic>CRLF2::P2RY8<\/jats:italic> rearrangement. He was treated as per Children's Oncology Group (COG) AALL1131 therapy and achieved a complete remission. Seven months after diagnosis, he was found to have papillary thyroid carcinoma with no evidence of metastatic disease. The patient underwent a total thyroidectomy with central lymph node biopsy and radioactive iodine therapy. The patient's biological mother and fraternal twin brother carry the same germline <jats:italic>CHEK2<\/jats:italic> mutation with no history of malignancy. The biological father tested negative for the familial mutation. The patient's genetic panel also identified three variants of unclear significance: <jats:italic>CDKN2A<\/jats:italic> (c.37\u2005\u00b0C\u2009&amp;gt;\u2009T; p.Arg124Cys), <jats:italic>FLCN<\/jats:italic> (c.62G\u2009&amp;gt;\u2009A; p.Cys21Tyr) and <jats:italic>SDHAF2<\/jats:italic> (c.139A\u2009&amp;gt;\u2009G; p.Met47Val). Extended family history also revealed a diagnosis of anaplastic thyroid cancer in maternal uncle at the age of 44 years. Fifteen months after diagnosis the patient had a relapse of B-ALL (both medullary and extramedullary with blasts in CSF), which was successfully treated with tisagenlecleucel. The patient remains in remission 3 years after receiving tisagenlecleucel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As conventional chemotherapy and radiation can potentially increase the risk of DNA damage and development of secondary malignancies, CD19 CAR-T therapy (tisagenlecleucel) can be used as a substitute for intensive re-induction chemotherapy and HCT in patients with a germline <jats:italic>CHEK2<\/jats:italic> mutation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2023.1067131","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T05:37:37Z","timestamp":1677649057000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case report: Tisagenlecleucel for treatment of relapsed B- acute lymphoblastic leukemia in a patient with CHEK2 mutation"],"prefix":"10.3389","volume":"11","author":[{"given":"Abraham","family":"Ipe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Angiolillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Jacobsohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinjun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Bornhorst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anant","family":"Vatsayan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2675","DOI":"10.3390\/cells9122675","article-title":"CHEK2 Germline variants in cancer predisposition: stalemate rather than checkmate","volume":"9","author":"Stolarova","year":"2020","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1086\/426403","article-title":"CHEK2 Is a multiorgan cancer susceptibility gene","volume":"75","author":"Cybulski","year":"2004","journal-title":"Am J Hum Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1897-4287-7-4","article-title":"The contribution of CHEK2 to the TP53-negative li-fraumeni phenotype","volume":"7","author":"Ruijs","year":"2009","journal-title":"Hered Cancer Clin Pract"},{"key":"B4","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1158\/0008-5472.CAN-21-1845","article-title":"Functional analysis identifies damaging CHEK2 missense variants associated with increased cancer risk","volume":"82","author":"Boonen","year":"2022","journal-title":"Cancer 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variants in myeloid and other hematopoietic malignancies","volume":"17","author":"Stubbins","year":"2022","journal-title":"Curr Hematol Malig Rep"},{"key":"B9","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.leukres.2018.05.013","article-title":"Constitutional mutations of the CHEK2 gene are a risk factor for MDS, but not for de novo AML","volume":"70","author":"Janiszewska","year":"2018","journal-title":"Leuk Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"17111","DOI":"10.1073\/pnas.0909237106","article-title":"Mice with the CHEK2*1100delC SNP are predisposed to cancer with a strong gender bias","volume":"106","author":"Bahassi el","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e000364","DOI":"10.1136\/jitc-2019-000364","article-title":"CAR T-cell therapy for a relapsed\/refractory acute B-cell lymphoblastic lymphoma patient in the context of li-fraumeni 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