Mutlu Kartal-Kaess, Axel Karow, Ulrike Bacher, Thomas Pabst, Raphael Joncourt, Christiane Zweier, Claudia E Kuehni, Naomi Azur Porret, Jochen Roessler
{"title":"在接受自体干细胞移植的儿童患者中,具有不确定潜能的克隆性造血非常罕见。","authors":"Mutlu Kartal-Kaess, Axel Karow, Ulrike Bacher, Thomas Pabst, Raphael Joncourt, Christiane Zweier, Claudia E Kuehni, Naomi Azur Porret, Jochen Roessler","doi":"10.1080/08880018.2024.2362885","DOIUrl":null,"url":null,"abstract":"<p><p>Clonal hematopoiesis of indeterminate potential (CHIP) describes recurrent somatic gene mutations in the blood of healthy individuals, associated with higher risk for hematological malignancies and higher all-cause mortality by cardiovascular disease. CHIP increases with age and is more common in adult patients after chemotherapy or radiation for cancer. Furthermore, in some adult patients undergoing autologous stem cell transplantation (ASCT) or thereafter, CHIP has been identified. In children and adolescents, it remains unclear how cellular stressors such as cytotoxic therapy influence the incidence and expansion of CHIP. We conducted a retrospective study on 33 pediatric patients mostly with solid tumors undergoing ASCT for presence of CHIP. We analyzed CD34+ selected peripheral blood stem cell grafts after several cycles of chemotherapy, prior to cell infusion, by next-generation sequencing including 18 \"CHIP-genes\". Apart from a somatic variant in <i>TP53</i> in one patient no other variants indicative of CHIP were identified. As a CHIP-unrelated finding, germline variants in <i>CHEK2</i> and in <i>ATM</i> were identified in two and four patients, respectively. In conclusion, we could not detect \"typical\" CHIP variants in our cohort of pediatric cancer patients undergoing ASCT. However, more studies with larger patient numbers are necessary to assess if chemotherapy in the pediatric setting contributes to an increased CHIP incidence and at what time point.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":" ","pages":"530-539"},"PeriodicalIF":1.2000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clonal hematopoiesis of indeterminate potential is rare in pediatric patients undergoing autologous stem cell transplantation.\",\"authors\":\"Mutlu Kartal-Kaess, Axel Karow, Ulrike Bacher, Thomas Pabst, Raphael Joncourt, Christiane Zweier, Claudia E Kuehni, Naomi Azur Porret, Jochen Roessler\",\"doi\":\"10.1080/08880018.2024.2362885\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Clonal hematopoiesis of indeterminate potential (CHIP) describes recurrent somatic gene mutations in the blood of healthy individuals, associated with higher risk for hematological malignancies and higher all-cause mortality by cardiovascular disease. CHIP increases with age and is more common in adult patients after chemotherapy or radiation for cancer. Furthermore, in some adult patients undergoing autologous stem cell transplantation (ASCT) or thereafter, CHIP has been identified. In children and adolescents, it remains unclear how cellular stressors such as cytotoxic therapy influence the incidence and expansion of CHIP. We conducted a retrospective study on 33 pediatric patients mostly with solid tumors undergoing ASCT for presence of CHIP. We analyzed CD34+ selected peripheral blood stem cell grafts after several cycles of chemotherapy, prior to cell infusion, by next-generation sequencing including 18 \\\"CHIP-genes\\\". Apart from a somatic variant in <i>TP53</i> in one patient no other variants indicative of CHIP were identified. As a CHIP-unrelated finding, germline variants in <i>CHEK2</i> and in <i>ATM</i> were identified in two and four patients, respectively. In conclusion, we could not detect \\\"typical\\\" CHIP variants in our cohort of pediatric cancer patients undergoing ASCT. However, more studies with larger patient numbers are necessary to assess if chemotherapy in the pediatric setting contributes to an increased CHIP incidence and at what time point.</p>\",\"PeriodicalId\":19746,\"journal\":{\"name\":\"Pediatric Hematology and Oncology\",\"volume\":\" \",\"pages\":\"530-539\"},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Hematology and Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/08880018.2024.2362885\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Hematology and Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08880018.2024.2362885","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/6 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Clonal hematopoiesis of indeterminate potential is rare in pediatric patients undergoing autologous stem cell transplantation.
Clonal hematopoiesis of indeterminate potential (CHIP) describes recurrent somatic gene mutations in the blood of healthy individuals, associated with higher risk for hematological malignancies and higher all-cause mortality by cardiovascular disease. CHIP increases with age and is more common in adult patients after chemotherapy or radiation for cancer. Furthermore, in some adult patients undergoing autologous stem cell transplantation (ASCT) or thereafter, CHIP has been identified. In children and adolescents, it remains unclear how cellular stressors such as cytotoxic therapy influence the incidence and expansion of CHIP. We conducted a retrospective study on 33 pediatric patients mostly with solid tumors undergoing ASCT for presence of CHIP. We analyzed CD34+ selected peripheral blood stem cell grafts after several cycles of chemotherapy, prior to cell infusion, by next-generation sequencing including 18 "CHIP-genes". Apart from a somatic variant in TP53 in one patient no other variants indicative of CHIP were identified. As a CHIP-unrelated finding, germline variants in CHEK2 and in ATM were identified in two and four patients, respectively. In conclusion, we could not detect "typical" CHIP variants in our cohort of pediatric cancer patients undergoing ASCT. However, more studies with larger patient numbers are necessary to assess if chemotherapy in the pediatric setting contributes to an increased CHIP incidence and at what time point.
期刊介绍:
PHO: Pediatric Hematology and Oncology covers all aspects of research and patient management within the area of blood disorders and malignant diseases of childhood. Our goal is to make PHO: Pediatric Hematology and Oncology the premier journal for the international community of clinicians and scientists who together aim to define optimal therapeutic strategies for children and young adults with cancer and blood disorders. The journal supports articles that address research in diverse clinical settings, exceptional case studies/series that add novel insights into pathogenesis and/or clinical care, and reviews highlighting discoveries and challenges emerging from consortia and conferences. Clinical studies as well as basic and translational research reports regarding cancer pathogenesis, genetics, molecular diagnostics, pharmacology, stem cells, molecular targeting, cellular and immune therapies and transplantation are of interest. Papers with a focus on supportive care, late effects and on related ethical, legal, psychological, social, cultural, or historical aspects of these fields are also appreciated. Reviews on important developments in the field are welcome. Articles from scientists and clinicians across the international community of Pediatric Hematology and Oncology are considered for publication. The journal is not dependent on or connected with any organization or society. All submissions undergo rigorous peer review prior to publication. Our Editorial Board includes experts in Pediatric Hematology and Oncology representing a wide range of academic and geographic diversity.