Cytogenetic profile of patients diagnosed with acute leukaemia in a resource-limited academic hospital, Ga-Rankuwa, South Africa

Abstract

Detection of genetic abnormalities in acute leukaemia (AL) by cytogenetic analysis is crucial to confirm the diagnosis and prognostication  of AL allowing personalised therapy and treatment response monitoring in a resource-limited setting. AL is classified into acute myeloid  leukaemia (AML), acute lymphoblastic leukaemia (ALL), and acute leukaemia of ambiguous lineage (ALAL). There is hardly any published  data on the cytogenetic profile of AL at Dr George Mukhari Academic Laboratory, Ga-Rankuwa, South Africa and there is limited  information on the success rate of cytogenetic testing in the country. This study aimed to describe the cytogenetic profile in patients with  AL and to examine the success rate of cytogenetic testing at Dr George Mukhari hospital’s laboratory. A cross-sectional review of  diagnosed cases of AL including children and adults was performed from July 2015 to June 2020. These results were extracted from the laboratory information system after obtaining ethical clearance. A total of 153 patients with AL satisfied the inclusion criteria. The  patients’ age categories were 0-12, 13-19, 20-35, 36-50, and those above 50 years, with a mean age of 29.8 ± 19.4 years. Statistical analyses  included frequencies and percentages undertaken to interpret categorical data according to their genetic abnormalities. The  Chi-square test was subsequently applied to analyse the frequency of the patients’ genetic abnormalities according to age, sex with AML,  and B-lymphoblastic leukaemia/lymphoma (B-ALL). The three main types of AL were AML, ALL, and ALAL. Interestingly, females  comprised most cases of AL. Expectedly, AML was more common in adults, and ALL was predominantly detected in children. The most  prevalent genetic abnormality in AML was the PML::RARA fusion gene with a high prevalence in adults, followed by RUNX1::RUNXT1 and CBFB::MYH11 fusion gene. Other genetic abnormalities included BCR::ABL1 and KMT2A rearrangement, detected mostly in adults. The  most prevalent genetic abnormality in B-ALL was the BCR::ABL1 fusion gene, detected mostly in adolescents and adults. This was  followed by KMT2A rearrangement which was equally seen in both children and adults. Other genetic abnormalities in B-ALL included the  ETV6::RUNX1 and TCF3::PBX1 fusion genes, as well as hyperdiploidy seen mostly in children, adolescents, and adults, respectively.  There was no statistically significant difference between age, sex, and genetic abnormalities in both AML and B-ALL (p>0.05). A high  prevalence of the BCR::ABL1 fusion gene was unexpected in AML and B-ALL and these results allowed for targeted therapy with tyrosine  kinase inhibitors in these patients. Therefore, cytogenetic testing remains crucial to diagnose and inform treatment choices for AL in  resourcelimited settings. Of concern was the high prevalence of unsuccessful cytogenetic results which requires further investigation to  promote the success rate of cytogenetic analysis.