Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa

dc.contributor.advisorShires, Karen
dc.contributor.authorJenkins, Nicholas
dc.date.accessioned2022-06-10T10:05:14Z
dc.date.available2022-06-10T10:05:14Z
dc.date.issued2022
dc.date.updated2022-06-10T10:04:56Z
dc.description.abstractIntroduction 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.apacitationJenkins, N. (2022). <i>Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa</i>. (). ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/36465en_ZA
dc.identifier.chicagocitationJenkins, Nicholas. <i>"Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa."</i> ., ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2022. http://hdl.handle.net/11427/36465en_ZA
dc.identifier.citationJenkins, N. 2022. Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa. . ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. http://hdl.handle.net/11427/36465en_ZA
dc.identifier.ris TY - Master Thesis AU - Jenkins, Nicholas AB - 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. DA - 2022 DB - OpenUCT DP - University of Cape Town KW - haematology LK - https://open.uct.ac.za PY - 2022 T1 - Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa TI - Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa UR - http://hdl.handle.net/11427/36465 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/36465
dc.identifier.vancouvercitationJenkins N. Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa. []. ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2022 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/36465en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Clinical Laboratory Sciences
dc.publisher.facultyFaculty of Health Sciences
dc.subjecthaematology
dc.titleCytogenetically normal acute myeloid leukaemia at a single centre in South Africa
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationlevelMMed
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