Cytogenetically Normal Acute Myeloid Leukaemia at a single centre in South Africa

Nicholas Jenkins, Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town and NHLS, Groote Schuur Hospital, South Africa
Lee-Ann Phillips, Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town and NHLS, Groote Schuur Hospital, South Africa
Marian Stone, Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town and NHLS, Groote Schuur Hospital, South Africa
Estelle Verburgh, Division of Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, South Africa
Jenna Oosthuizen, Division of Haematology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Groote Schuur Hospital, South Africa
Karen Shires, Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town and NHLS, Groote Schuur Hospital, South AfricaFollow

Abstract

Background: The heterogeneous molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge. The European Leukaemia Net 2017 guidelines attempted 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. Objectives: 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 risk stratification in accordance with the ELN 2017 guidelines, using nucleophosmin (NPM1), fms-like tyrosine kinase internal tandem duplication (FLT3-ITD) and CCAAT/enhancer binding protein alpha (CEBPα) mutation status. Methods: A review of cytogenetic results for adult de novo AML cases diagnosed at Groote Schuur Hospital between 2005 and 2018 was performed. CN-AML cases were further characterized via by a review of clinical and laboratory data and additional molecular testing on stored DNA samples to allow for mutation-based risk stratification and outcome analysis Results : In total, 218 patients with AML were identified of which 33% were cytogenetically normal. NPM1, FLT3-ITD and CEBPα mutations were found in 39%, 34% and 9% of CN-AML cases respectively. Retrospective risk stratification according to mutations in these 3 genes accurately identified both patients at a high risk of induction-resistant disease and those who required an allogeneic SCT in CR1. Conclusion: Local rates of CN-AML and associated NPM1 and FLT3-ITD mutations were comparable to European cohorts. Limited mutation analysis in the form of triple mutation testing proved to be an economical and therapeutically informative prognostication approach for CN-AML in a resource limited setting.

Recommended Citation

Jenkins, Nicholas; Phillips, Lee-Ann; Stone, Marian; Verburgh, Estelle; Oosthuizen, Jenna; and Shires, Karen (2023) "Cytogenetically Normal Acute Myeloid Leukaemia at a single centre in South Africa," Hematology/Oncology and Stem Cell Therapy: Vol. 16 : Iss. 4 , Article 15.
Available at: https://doi.org/10.56875/2589-0646.1087