Baxter, Jayson McNeil2024-11-122024-11-122024Baxter, Jayson McNeil. (2024). A 15 -Year Review of Multiple Myeloma in HIV-1 Seropositive Patients at Chris Hani Baragwanath Academic Hospital [Master’s dissertation, University of the Witwatersrand, Johannesburg]. WireDSpace.https://hdl.handle.net/10539/42356https://hdl.handle.net/10539/42356A research report submitted in partial fulfillment of the requirements for the degree of Master of Medicine (Internal Medicine) to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2024Background: Multiple Myeloma (MM) is a haematological malignancy characterized by the malignant proliferation of plasma cells in the bone marrow and manifesting with skeletal related events as the clinical and radiological hallmark of the disease. The incidence of MM varies substantially across the different continents, with intermediate rates being encountered in Africa. MM occurs more commonly in people of Afro-Caribbean descent, with the incidence being 2-fold higher in African Americans compared to Caucasians. In South Africa, prior to the advent of and impact of HIV, MM was the most common haematological malignancy in adults. However, since 2002, Non-Hodgkin Lymphoma (NHL) has superseded MM, with MM being the second most common haematological malignancy encountered in adults, currently. At Chris Hani Baragwanath Academic Hospital (CHBAH), MM has been a stable disease since the 1970’s, with a noticeable increase in numbers since 2016. MM is characteristically a disease of middle-aged and elderly individuals. In the Western world, ninety-eight percent of cases occur over the age of 40 years with a peak in incidence in the seventh decade. The median age at diagnosis is 66 years. However, in Africa, the disease presents at a younger median age (approximately 5-10 years younger), with 7% of the patients being under the age of 40 years. In 2020, globally there were 36 million adults with HIV-1 of which 67% were living in sub- Saharan Africa. Women accounted for 63% of all new HIV-1 infections, compared to men with 37%. South Africa has the highest number of HIV-1 sero-positive individuals in the world and is home to approximately 8 million people living with HIV (PLWH). In South Africa, HIV has reached epidemic proportions and is impacting on a number of haematological malignancies, including MM. This study was undertaken to better characterize and describe the demographics, clinical, laboratory and radiological findings of patients presenting with HIV-1 sero-positivity and concomitant MM in our patient population. In addition, it describes the therapy, response to therapy, outcome and survival of the patients with this association. b. Patients and Methods: This is a retrospective study of all adult patients with a confirmed diagnosis of MM, together with HIV-1 sero-positivity, seen at the Clinical Haematology Unit, Department of Medicine, from January 2006 to December 2020 (15 years). Demographic, clinical, radiological and therapeutic data was retrieved from the patient files and laboratory data from the NHLS data base. Data was processed in Microsoft Excel and the appropriate statistical software was used to analyse the results. Descriptive analysis was conducted through the computation of frequency tables for categorical variables and appropriate measures of central tendency, i.e., mean, ± SD/median and (IQR), for continuous variables. Kaplan-Meier survival curves were plotted to determine the survival probability of the patients based on the clinical, laboratory and treatment characteristics. c. Results and Discussion: During the study period (01/01/2006 to 31/12/2020 – 15 years), a total of 601 patients were diagnosed with MM. 84 patients were HIV-1 seropositive (14%). Of these 84 patients, 14 were excluded. A total of 70 evaluable HIV-1 seropositive patients were included in this study (12%). Of these 70 patients, there were 42 females and 28 males with a female to male ratio of 1.5:1. The mean age for females was 49.9 years (range 31-77 years), and males was 50.6 years (range 36-73 years), while the mean age for the whole group was 50.2 years (range 31-77years). All the patients in the study were of Black African ethnicity, in keeping with the demographic of CHBAH, where >90% of the patients admitted to the hospital are of Black African ethnicity. The pertinent findings in this study were the following: 1. An increase in the number of MM patients from 165 (2006-2010) and 168 (2011-2015), to 268 (2016-2020), in the latter five years of the study. A corresponding increase in HIV seropositivity of 10.9% (2006-2010) and 10.1% (2011-2015), to 18.3% (2016-2020) in the latter 5 years of the study, with a background seroprevalence in Gauteng of 14.9% (2005) to14.4% (2008) and 18.8% (2012) to 18.7% (2017), 2. A younger mean age of 50 years, with a female predominance of 1.5:1, 3. More than half the patients (54.7%) had an ECOG PS ≥2, 4. Bone pain and anaemia were the dominant clinical features, 5. A higher proportion of cytopenias, including leucopenia, neutropenia and thrombocytopenia was noted in the study population compared to other studies done locally at CHBAH on MM. 6. Plasmacytomas were evident clinically in 29% of patients and radiologically in 52% of patients. 7. Biochemical features of note were: hypercalcaemia in 56% of patients, renal dysfunction in 33% of patients, hypoalbuminaemia in 65% of patients and an elevated B2M level in 96.3% of the patients. The mean CD4 count was 367 cells/ul, with a range of 23-964 cells/ul. Approximately a quarter of the patients (26.1%) had a CD4 count <200 cells/ul, 8. IgG isotype (74%) was the most common subtype of MM, 9. Lytic lesions were found in up to 77% of the patients on CT scan, with vertebral compression fractures being present in 77% of patients on MRI. 10. Most patients had advanced stage of disease, with DS stage III in 92% of the patients and ISS stage III in 70% of the patients. 11. Specific therapy in the form of chemotherapy (different combinations of cytotoxics, corticosteroids and immunomodulatory agents such as thalidomide etc.) was administered to 76% of the patients. Furthermore, 34% had radiotherapy and only 6% had an ASCT, 12. Despite the use of cART and specific therapy, the overall outcome was poor, with a median survival of 5.64 months (Interquartile range 0.82-19.24 months), 13. Survival was statistically significantly better in those who received chemotherapy and/or radiotherapy compared to those who received supportive care only (p=<0.001) and those who had ISS stage I and II disease, compared to ISS stage III disease (p=0.006), and 14. Although survival was better in those who had a higher CD4 count (≥200 cells/ul versus <200 cells/ul) (p=0.081), and those who achieved at least a PR versus <PR (p=0.108), these two parameters were not statistically significantly different. d: Conclusions and Future recommendations: Although chronic antigenic stimulation and immunodeficiency in HIV-1 sero-positive individuals may contribute to an increased risk of MM, it is unclear whether the association between the two diseases in our patients, is causal or coincidental. Nevertheless, what is apparent is that this association is increasing (18% in the latter five years of the study). As such, we need to create awareness of this, so that the patients can be recognized, diagnosed and treated timeously, in order to improve the prognosis and outcomes of the patients. It is clear from this study, that MM in association with HIV-1 sero-positivity presents in younger individuals, with a female predominance, with typical and characteristic features of bone pain, anaemia, lytic bone lesions, vertebral compression fractures, hypercalcaemia, renal dysfunction, as well as more frequent extramedullary manifestations such as plasmacytomas, predominance of an IgG isotype, advanced stage disease and inferior outcomes. Future recommendations should include: Continued efforts to prevent, minimize and lessen the burden of HIV, together with early initiation of antiretroviral therapy, recognition of, and aggressive and optimal management of complications of the disease. Education with regard to the key clinical manifestations of MM, early suspicion of the diagnosis and timeous referral to a tertiary or specialized centre, so that treatment can be initiated as soon as possible. Appropriate follow up of the patients 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. Increase the number of patients who require an ASCT, as part of consolidation treatment. Furthermore, prospective, multicentre studies need to be undertaken to optimally manage HIV- 1 sero-positivity in association with MM. 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.en© 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.Multiple Myeloma (MM) iHematological malignancyHIV-1 Seropositive PatientsUCTDSDG-3: Good health and well-beingDissertationUniversity of the Witwatersrand, Johannesburg