Khosa, Cain Mikateko2024-11-132024-11-132024Khosa, Cain Mikateko . (2024). A fifteen year review of chronic lymphocytic leukaemia in adults, at Chris Hani Baragwanath academic hospital [Master’s dissertation, University of the Witwatersrand, Johannesburg]. WireDSpace.https://hdl.handle.net/10539/42403A research report submitted in partial fulfillment of the requirements for the degree of Master of Medicine in Internal Medicine to the Faculty of Health Sciences, School of Clinical MedicineUniversity of the Witwatersrand, Johannesburg,Johannesburg, June 2024Background: Chronic Lymphocytic Leukaemia (CLL) is one of the four common types of leukaemia encountered in adults. CLL is characterized by the clonal proliferation and accumulation of small, mature, neoplastic, CD-5 positive, B-lymphocytes in the blood, bone marrow and lymphoid tissues. There are geographical variations in the incidence of CLL worldwide, with CLL being the commonest form of leukaemia in some parts of Europe and the Western World. The median age at diagnosis is approximately 70 years, with less than 10% of patients presenting under 45 years of age. Most studies show a male predominance of 1.5-1.9:1. While the incidence in Europe is similar to that reported in the United States, the incidence is lower in Asia and Africa. Moreover, in Africa, the disease tends to present in individuals who are 5-10 years younger, primarily because of the younger age structure of the African population. At Chris Hani Baragwanath Academic Hospital (CHBAH), CLL ranks 5th in order of frequency, amongst the haematological malignancies that are encountered in adult patients. Based on a small study done at CHBAH in 1994, the disease presents at a younger median age of 63 years, with a male predominance of 1.5:1. Although CLL is generally a stable disease at CHBAH, there has been a noticeable increase in the number of patients by 1.5 fold, from 2015 to 2019. This study was undertaken to better characterize and describe the demographics, clinical and laboratory features, staging and treatment outcome of adult patients with CLL, seen at our centre over a 15 year period. b. Patients and Methods: This was a retrospective study of all adult patients with a confirmed diagnosis of CLL, seen over a 15 year period (01/01/2005 to 31/12/2019), at the Clinical Haematology Unit, Department of Medicine, CHBAH (15 years). Demographic, clinical, and therapeutic data was retrieved from the patient files and laboratory data from the NHLS data base. Data was obtained retrospectively from patient files, captured onto a data sheet and entered onto an Excel spread sheet prior to statistical analysis, using a programme such as Stata/Statistica (and/with the assistance of a statistician). The patient demographics were summarized using descriptive statistics for dependent variables that are normally distributed, including means and standard deviations. For comparisons between normally distributed variables, a Student t-test was be used. For comparing the different staging systems, a Chi squared test was used. Where a comparison was required in more than two groups, the Anova test was used. When data was not normally distributed, the Mann-Whitney or Kruskal-Willis test was used for correlation between variables. For the purpose of statistical analysis, a 95% confidence interval, with a p-value (p<0.05) was considered significant c. Results and Discussion: The key findings in this study were: 1. A stable number of patients in the first ten years of the study (01/01/2005 to 31/12/2014), with a 1.5 fold increase in the latter 5 years of this study (2015-2019). 2. A younger median age of 64 years, with a male predominance of 1.87:1. 3. Most of the patients were symptomatic, with an ECOG PS ≥1 in 92.8% of the patients. 4. Fatigue (49.2%), loss of weight (47%) and fever (43%) were the most common symptoms at presentation. 5. Lymphadenopathy was the dominant physical sign (91.2%). Hepatosplenomegaly was evident in 49.2% of the patients. 6. The vast majority of patients had anaemia (82.9%), with a mean haemoglobin of 9.44 g/dl. The mean white cell count and lymphocyte counts were 173 x109/l and 158.7 x 109/l, respectively. The mean platelet count was 155 x 109/l. Clinical thrombocytopenia was present in 37% of the patients. 7. More than half the patients presented with advanced stage/high risk disease, with a Rai stage III and IV accounting for 62.5% and Binet C for 56.4% of the patients at presentation. 8. A diffuse pattern of bone marrow infiltration, indicating adverse prognosis was evident in 89.5% of the patients. 9. Cytogenetics showed a favourable genotype (13q) in 43%, an intermediate phenotyope (trisomy 12) in 31.7% and an unfavourable phenotype (11q and 17p) in 14% and 11%, of the patients, respectively. 10. HIV sero-positivity was present in 8.8% of the patients, with sero-positive patients showing a number of differences, including a younger median age at presentation, a more marked male predominance, similar clinical presentation and staging of the disease, a higher proportion of TB, hepatitis B and C, and a lower mean survival, with a similar median survival. 11. Supportive care only was offered to 22.7%, while chemotherapy was administered to 69% of the patients. 12. The outcomes of the patients at the end of study were: i) Lost to follow up (65.2%), ii) Deceased (31.5%) and Alive (3.3%). 13. The mean survival for the whole group was 32 months, with a median survival of 6 months, while for the HIV sero-positive group the median survival was 20 months, with a median survival of 6 months. d. Conclusions and future recommendations: Based on the findings of this study, the following conclusions and future recommendations are suggested: Education with regard to the key clinical manifestations of CLL, early suspicion of the possible diagnosis and timeous referral to a tertiary or specialized centre, so that the diagnosis can be confirmed and appropriate treatment (where indicated), can be initiated as soon as possible. Every effort should be made to improve compliance and attendance at follow up visits. This is vital in order to assess response to treatment and to detect early relapse or progression of the disease. Efforts to improve accessibility of ‘state of the art’ and novel therapies for public sector patients should be prioritised and ongoing. Prospective, randomised, multi-centre studies should be performed to assess the benefits of various therapeutic options and to compare existing therapies with novel treatment options in our local South African patient population (including both the private and public sector). Although HIV sero-positivity is not a major problem, the numbers of sero-positive patients is steadily increasing, with a doubling of the number in the latter 5 years, compared to the first 10 years of the study. In principle, these patients should be offered the same treatment options as HIV-1 sero-negative individuals, with the proviso that every attempt is made to achieve optimal virological suppression and immune reconstitution, with combination anti- retroviral therapen© 2024 University of the Witwatersrand, Johannesburg. All rights reserved. The copyright in this work vests in the University of the Witwatersrand, Johannesburg. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of University of the Witwatersrand, Johannesburg.Chronic Lymphocytic Leukaemia (CLLUCTDSDG-3: Good health and well-beingDissertationUniversity of the Witwatersrand, Johannesburg