Masters Degrees (Haematology)
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Item The prognostic of CD38 and CD49d flow cytometry markers in chronic lymphocytic leukemia: a retrospective 5-year study.(2023) Voxeka, Siyabonga Eric.; Murugan, Stephanie.; Rapiti, Nadine.Background: The prognosis of chronic lymphocytic leukemia (CLL) is determined by various prognostic markers. The importance of the immunophenotypic markers CD38 and CD49d on flow cytometry in CLL is well-established internationally. However, there is no data from South Africa on these markers. Objective: This study assessed the frequency of CD38 and CD49d expression in newly diagnosed CLL patients, and the correlation of these markers with other prognostic variables. Methods: A 5-year retrospective analysis was performed on all newly diagnosed CLL patients. The expression of CD38 and CD49d were correlated with haemoglobin concentration, platelet counts and markers by Fluorescence in situ hybridisation (FISH) analysis. Patient charts were obtained from the haematology clinic for 2-year overall survival (OS) analysis, and described using Kaplan-Meier survival curves. Results: Data from 86 newly diagnosed CLL patients were analyzed. Most of the patients, 70.9% (n=61), were between 60-79 years of age. The frequency of CD38 positivity was 29% (n=25), CD49d positivity was 15.1% (n=13), dual positivity for CD38 and CD49d was 15.1% (n=13) and dual negativity was 40.7% (n=35). Of the 37% (n=33) who had CLL FISH studies, seven had 13q deletion, ten had trisomy 12 and two had 11q deletion. CD49d expression correlated with trisomy12 with (p value 0.002). Conclusion: The incidence of CD49d expression in KwaZulu-Natal, was lower than that described in CLL internationally. Although there was some correlation with molecular abnormalities detected by FISH, further prospective studies are warranted to confirmif these immunophenotypic markers can be utilized as surrogate prognostic markers in CLL.Item Distribution of PML-RARA isoforms in Acute promyelocytic leukemia patients from a tertiary hospital in KZN, South Africa using qPCR.(2017) Safiya, Ebrahim.; Gordon, Michelle Lucille.; Parsanath, Sharlene.The study of genetic epidemiology of cancers in Africa is unique as compared to first world countries, as it entails the combination of gene-environment interaction, poor socio-economic conditions and the high prevalence of infectious (e.g. tuberculosis and HIV) and non-infectious diseases. Acute Promyelocytic Leukemia (APL), a subtype of Acute Myeloid leukemia (AML) if not diagnosed within 24 hours because of its hemorrhagic tendencies, becomes a medical emergency. It has become one of the most treatment-responsive cancers due to its excellent response to all trans-retinoic acid (ATRA). Advances in molecular diagnostics have resulted in a reversetranscriptase polymerase chain reaction (RT-PCR) test to detect the PML-RARA (retinoic acid receptor alpha) transcript found in APL’s. Globally, many centers have investigated the different breakpoint cluster regions (bcr) to classify the patients into different prognostic groups for specific molecular targeted treatment. However, there are no reports from Africa on the frequency of the different isoforms in APL patients. In this study we aim to identify and determine the frequency of bcr isoforms in APL patients from a tertiary hospital in Kwa Zulu Natal (KZN) by quantitative RT-PCR (qPCR). The correlation of the hematological parameters with the different isoforms was analyzed by descriptive non-parametric statistical analysis. The qPCR confirmed bcr1 to be the predominant isoform (63,6%) followed by bcr3 (31,8%) and bcr2 (4,5%). There was a median age group of less than 45 in our patient cohort. Patients with the bcr3 isoform had a poor prognosis according to their clinical risk stratification but this did not necessarily result in poor overall survival when monitored for minimal residual disease (MRD). The HIV-infected APL patients with different isoforms responded to “standard of care” treatment in the same way as noninfected HIV patients.Item Coagulation system abnormalities in human immunodeficiency virus (HIV) positive African (Black) patients with acute upper segment deep vein thrombosis(DVT) of the lower limbs.(2006) Bassa, Fatima Cassim.; Poovalingam, V.Background Several case reports and studies have alluded to an increased prevalence of venous thrombosis in human immunodeficiency virus positive (HIV-positive) patients. Although a relationship between HIV infection and thrombotic disease has been suggested, the mechanisms predisposing to thrombosis have not been fully elucidated. Aim A prospective study, to determine possible coagulation factor abnormalities that could explain the predisposition to thrombosis in HIV-infected African (Black) patients, was undertaken. Method African (Black) patients, with acute upper segment deep vein thrombosis (DVT) confirmed by duplex ultrasound, were enrolled. Patients who had recognisable risk factors such as recent surgery, pregnancy or malignancy, were excluded. After informed consent, blood samples were taken for baseline tests as well as a thrombophilia screen. The control group comprised known HIV-positive African (Black) patients without DVT. Patients with DVT who were found to be HIV-negative were also analysed. Analysis was done in 2 parts: HIV-positive patients with and without thrombosis and HIV-positive and negative patients with thrombosis were compared. Results Part A: HIV-positive patients with and without thrombosis Of the 77 patients with DVT, 50 patients tested HIV-positive. These 50 patients (HIV-positive DVT-arm), as well as 56 controls (HIV-positive, no DVT), were enrolled into the study. The groups were well matched with regard to age, sex and cluster designation 4 (CD4) count. On univariate analysis, significant findings in the DVT-arm were a history of active tuberculosis on treatment, low protein C levels and a positive qualitative D-dimer, whereas on multivariate analysis, only tuberculosis and an elevated D-dimer proved to be significant. Part B: HIV-positive and negative patients with thrombosis There were 20 HIV-negative patients with DVT who met our inclusion criteria Limited assessment was done on this group owing to unavailability of some data. The mean age of the HIV positive DVT group was significantly lower than the HIV-negative group with DVT (31.78 vs. 41.45 years; p=0.005). There was no significant difference in the prevalence of tuberculosis between the HIV-positive and HIV-negative patients with thrombosis (p = 0.269). Mean protein C levels were reduced in the HIV-positive group and normal in the HIV-negative group. They were significantly lower in the HIV-positive patients compared to the negative group (p=0.02). Conclusion The findings of the study suggest a relationship between HIV, its complications and DVT. Although this study confirms HIV infection as a risk factor for thrombosis, clear pathogenetic mechanisms remain to be elucidated. In our population, tuberculosis appears to be an important risk factor predisposing patients to the development of DVT, both in the HIVpositive and negative population. Further studies will need to be done to confirm this hypothesis.