{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/36465"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/36465","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa","abstract":"Introduction The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge worldwide. The latest European LeukaemiaNet (ELN) 2017 guidelines attempt to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains elusive due to limited local data. This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological, molecular and treatment outcomes and consequently investigate the local applicability of a triple mutation testing approach for nucleophosmin (NPM1), fms-like tyrosine kinase internal tandem duplication (FLT3-ITD) and CCAAT/enhancer binding protein alpha (CEBPα) mutations in accordance with the ELN 2017 guidelines. Methods A review of cytogenetic results for all adult de novo AML cases diagnosed at Groote Schuur Hospital between 2005 and 2018 was performed. CN-AML cases were further characterized via molecular testing and review of clinical and laboratory data. Results In total, 218 patients with AML were identified of which fifty-six (33%) were cytogenetically normal. NPM1, FLT3-ITD and CEBPα mutations were found in 39%, 34% and 9% of CN-AML cases respectively, and allowed for definitive prognostication of 50% of cases. The 2-year overall survival rate for the entire CN-AML cohort was 16%. Conclusion Local rates of CN-AML and associated NPM1 and FLT3-ITD mutations were comparable to European cohorts. In contrast, local survival outcomes were notably inferior. Triple testing proved a resource effective prognostication approach for CN-AML. High throughput sequencing for adverse risk mutations should be considered for CN-AML patients inconclusively stratified via triple testing.","abstract_html":"Introduction The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge worldwide. The latest European LeukaemiaNet (ELN) 2017 guidelines attempt to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains elusive due to limited local data. This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological, molecular and treatment outcomes and consequently investigate the local applicability of a triple mutation testing approach for nucleophosmin (NPM1), fms-like tyrosine kinase internal tandem duplication (FLT3-ITD) and CCAAT/enhancer binding protein alpha (CEBPα) mutations in accordance with the ELN 2017 guidelines. Methods A review of cytogenetic results for all adult de novo AML cases diagnosed at Groote Schuur Hospital between 2005 and 2018 was performed. CN-AML cases were further characterized via molecular testing and review of clinical and laboratory data. Results In total, 218 patients with AML were identified of which fifty-six (33%) were cytogenetically normal. NPM1, FLT3-ITD and CEBPα mutations were found in 39%, 34% and 9% of CN-AML cases respectively, and allowed for definitive prognostication of 50% of cases. The 2-year overall survival rate for the entire CN-AML cohort was 16%. Conclusion Local rates of CN-AML and associated NPM1 and FLT3-ITD mutations were comparable to European cohorts. In contrast, local survival outcomes were notably inferior. Triple testing proved a resource effective prognostication approach for CN-AML. High throughput sequencing for adverse risk mutations should be considered for CN-AML patients inconclusively stratified via triple testing.","abstract_has_math":false,"creators":["Jenkins, Nicholas"],"institution":"Department of Clinical Laboratory Sciences","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Shires, Karen"],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022","date_published":"2022","updated_at":"2026-07-22T22:22:51Z","subjects":["haematology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/36465","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Shires, Karen"]},{"key":"dc:creator","label":"Author","values":["Jenkins, Nicholas"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2022-06-10T10:05:14Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2022-06-10T10:05:14Z"]},{"key":"dc:date.issued","label":"Date","values":["2022"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Clinical Laboratory Sciences"]},{"key":"dc:type","label":"Dc Type","values":["Master Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Masters","MMed"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["haematology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11427/36465"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Introduction The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge worldwide. The latest European LeukaemiaNet (ELN) 2017 guidelines attempt to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains elusive due to limited local data. This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological, molecular and treatment outcomes and consequently investigate the local applicability of a triple mutation testing approach for nucleophosmin (NPM1), fms-like tyrosine kinase internal tandem duplication (FLT3-ITD) and CCAAT/enhancer binding protein alpha (CEBPα) mutations in accordance with the ELN 2017 guidelines. Methods A review of cytogenetic results for all adult de novo AML cases diagnosed at Groote Schuur Hospital between 2005 and 2018 was performed. CN-AML cases were further characterized via molecular testing and review of clinical and laboratory data. Results In total, 218 patients with AML were identified of which fifty-six (33%) were cytogenetically normal. NPM1, FLT3-ITD and CEBPα mutations were found in 39%, 34% and 9% of CN-AML cases respectively, and allowed for definitive prognostication of 50% of cases. The 2-year overall survival rate for the entire CN-AML cohort was 16%. Conclusion Local rates of CN-AML and associated NPM1 and FLT3-ITD mutations were comparable to European cohorts. In contrast, local survival outcomes were notably inferior. Triple testing proved a resource effective prognostication approach for CN-AML. High throughput sequencing for adverse risk mutations should be considered for CN-AML patients inconclusively stratified via triple testing."]},{"key":"dc:title","label":"Title","values":["Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa"]}]}],"canonical_facts":{"dc:contributor.advisor":["Shires, Karen"],"dc:creator":["Jenkins, Nicholas"],"dc:date.accessioned":["2022-06-10T10:05:14Z"],"dc:date.available":["2022-06-10T10:05:14Z"],"dc:date.issued":["2022"],"dc:description.abstract":["Introduction The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge worldwide. The latest European LeukaemiaNet (ELN) 2017 guidelines attempt to address this by guiding post-remission therapy according to six prognostically informative mutations. However, its applicability in a South African setting remains elusive due to limited local data. This retrospective study aimed to describe a South African CN-AML cohort according to clinicopathological, molecular and treatment outcomes and consequently investigate the local applicability of a triple mutation testing approach for nucleophosmin (NPM1), fms-like tyrosine kinase internal tandem duplication (FLT3-ITD) and CCAAT/enhancer binding protein alpha (CEBPα) mutations in accordance with the ELN 2017 guidelines. Methods A review of cytogenetic results for all adult de novo AML cases diagnosed at Groote Schuur Hospital between 2005 and 2018 was performed. CN-AML cases were further characterized via molecular testing and review of clinical and laboratory data. Results In total, 218 patients with AML were identified of which fifty-six (33%) were cytogenetically normal. NPM1, FLT3-ITD and CEBPα mutations were found in 39%, 34% and 9% of CN-AML cases respectively, and allowed for definitive prognostication of 50% of cases. The 2-year overall survival rate for the entire CN-AML cohort was 16%. Conclusion Local rates of CN-AML and associated NPM1 and FLT3-ITD mutations were comparable to European cohorts. In contrast, local survival outcomes were notably inferior. Triple testing proved a resource effective prognostication approach for CN-AML. High throughput sequencing for adverse risk mutations should be considered for CN-AML patients inconclusively stratified via triple testing."],"dc:identifier.uri":["http://hdl.handle.net/11427/36465"],"dc:publisher.department":["Department of Clinical Laboratory Sciences"],"dc:subject":["haematology"],"dc:title":["Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa"],"dc:type":["Master Thesis"],"dc:type.qualificationlevel":["Masters","MMed"]},"updated_at":"2026-07-22T22:22:51Z"}