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Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa
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 progn...
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| Format: | Thesis |
| Language: | English |
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Department of Clinical Laboratory Sciences
2022
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| _version_ | 1867613206969581568 |
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| access_status_str | Open Access |
| author | Jenkins, Nicholas |
| author2 | Shires, Karen |
| author_browse | Jenkins, Nicholas Shires, Karen |
| author_facet | Shires, Karen Jenkins, Nicholas |
| author_sort | Jenkins, Nicholas |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/36465 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:27.580Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Department of Clinical Laboratory Sciences |
| publisherStr | Department of Clinical Laboratory Sciences |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/36465 Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa Jenkins, Nicholas Shires, Karen haematology 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. 2022-06-10T10:05:14Z 2022-06-10T10:05:14Z 2022 2022-06-10T10:04:56Z Master Thesis Masters MMed http://hdl.handle.net/11427/36465 eng application/pdf Department of Clinical Laboratory Sciences Faculty of Health Sciences |
| spellingShingle | haematology Jenkins, Nicholas Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa |
| thesis_degree_str | Master's |
| title | Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa |
| title_full | Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa |
| title_fullStr | Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa |
| title_full_unstemmed | Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa |
| title_short | Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa |
| title_sort | cytogenetically normal acute myeloid leukaemia at a single centre in south africa |
| topic | haematology |
| url | http://hdl.handle.net/11427/36465 |
| work_keys_str_mv | AT jenkinsnicholas cytogeneticallynormalacutemyeloidleukaemiaatasinglecentreinsouthafrica |