An analysis of cytogenetic and molecular abnormalities in patients with Acute Myelogenous Leukaemia at the Charlotte Maxeke Johannesburg Academic Hospital (2013 – 2016)
Date
2020
Authors
Debising, Mohith
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Abstract
Introduction:
Acute Myeloid Leukaemia (AML) is a heterogenous disease with a relatively low incidence
worldwide but a disproportionately high mortality rate. Despite modern advances and improved
understanding of the disease the overall survival statistics of those afflicted by AML is still poor.
Increasing weight is placed on cytogenetic and molecular analyses of patients’ specific
malignancies through new research findings, allowing for the improvement in prognostication of
these patients. In the past few years, a number of new treatments, targeting these abnormalities,
have been approved for use, or are currently in development, in the management of AML. In
addition, our improved understanding of the prognosis of this disease based on cytogenetic and
molecular mutations now allows us to fast-track patients with a high risk for relapse post induction
toward haemopoietic stem cell transplantation.
Aims:
The aim of the study was to review the specific cytogenetic and molecular mutational trends in
patients managed at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) as well as in
samples submitted to the National Health and Services Laboratory (NHLS) from surrounding
hospitals from January 2013 to May 2016. The study also involved a review of management and
survival outcomes in AML patients managed at CMJAH.
Methods:
A retrospective review was undertaken of cytogenetic and molecular analyses of bone marrow and
peripheral blood specimens in patients diagnosed with AML submitted to the NHLS and a review
of patients’ files and treatment records of patients managed for AML at CMJAH. The study analysed two separate data subsets, one cohort (Cohort A) analysing cytogenetic and mutational
abnormalities and outcomes in patients treated at CMJAH and the other cohort (Cohort B)
analysing only molecular mutational abnormalities for patients from surrounding hospitals.
Results:
Cohort A analysed 65 patients, with a median age at diagnosis of 43 years old (range 16 - 74 years)
and found most patients (71%) to have abnormal cytogenetics. The most commonly encountered
cytogenetic abnormality wast(8;21) translocation seen in 20% of patients. According to prognostic
risk stratification most of these patients fell within the favourable prognostic grouping. For this
cohort of 65 patients, only one patient had no records available for review of treatment and
outcome. Of the remaining 64 patients, 48 patients (75%) underwent chemotherapy as part of their
disease management, with 36 (75%) patients surviving initial treatment. Of those who survived
induction therapy, 20 patients (56%) achieved a complete remission (CR). Overall one year
survival was found to be 43% (95% confidence interval (CI): 29% - 57%) for the group as a whole
with a significant difference (HR=0.34; 95% CI: 0.16 – 0.73; p=0.0058) seen between the survival
of those who received chemotherapy and those who were managed conservatively.
Cohort B analysed a total of 188 patients, revealing a median age at diagnosis of 47 years old
(range 14 – 85 years). The most commonly encountered mutation was of Nucleophosmin 1 (NPM
1) (37 of 188 patients) followed by (FMS-like tyrosine kinase 3) FLT 3 (34 of 188 patients).
Mutations of both NPM 1 and FLT 3 were found to be present in 11 patients (6% of this cohort).
Conclusions:
Our study findings were found to be similar to those seen internationally for upper middle income
countries (UMICs) and lower middle income countries (LMICs), yielding similar disease patterns to those of studies undertaken in Brazil and Malaysia. Moreover, the study confirmed the
differences in AML epidemiology seen between high income countries (HICs) and UMICs and
LMICs. To illustrate this, the cytogenetic analysis in our study revealed the highest prevalence of
patients in the age group 20 – 30 years of age, similar to findings in Brazil and Malaysia. On the
other hand, studies in the UK and USA, both HICs, reveal AML as a disease of older people of
age 60 years and older. The higher incidence of core binding factor (CBF) AML seen in younger
patients was also found in Cohort A (20% of patients positive for t(8;21) cytogenetic abnormality)
similar to epidemiology trends in other UMICs and LMICs
Description
A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the Degree of Master of Medicine (MMed)