HIV-associated thrombotic thrombocytopenic purpura (HIV-TTP): A practical guide and review of the literature.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP), a serious thrombotic microangiopathy (TMA), is prevalent in the South African HIV-infected population. The exact pathogenesis of HIV-associated TTP (HIV-TTP) is however still unclear with diagnostic and therapeutic inconsistancies. METHODS: A systematic review of the published literature regarding HIV-TTP was performed. RESULTS: HIV-TTP is still associated with significant morbidity and mortality in Africa despite the availability of anti-retroviral therpy (ART). Diagnosis of HIV-TTP requires the presence of a micro-angiopathic haemolytic anaemia with significant red blood cell schistocytes and thrombocytopenia in the absence of another TMA but background activation of the coagulation system and inflammation in HIV infected people can result in diagnostic anbiguity. Plasma therapy in the form of infusion or exchange is successful but expensive, associated with side-effects and not widely available. Adjuvant immunosuppression therapy may of benefit in patients with HIV-TTP and ART must always be optimised. Endothelial dysfunction caused by chronic inflammation and complement activation most likely contributes to the development of HIV-TTP. CONCLUSION: The role of adjuvant immunomodulating therpy, the therapeutic targets and pathogenic contribution from endothelial dysfunction in HIV-TTP requires further investigation.

Von Willebrand Factor Multimer Patterns in People Living with Human Immunodeficiency Virus Infection.

BACKGROUND: Endothelial dysfunction contributes to hypercoagulability in people with HIV (PWH). A surrogate marker of this is elevated von Willebrand factor (VWF) which has been documented in PWH. This study compared VWF multimer patterns in PWH who were anti-retroviral therapy (ART) naive and immune reconstituted on ART. METHODS: VWF multimer analysis was performed with a semi-quantitative electrophoresis assay on plasma from 79 PWH (39 ART-naive and 40 virally suppressed on ART) and 25 normal control samples. RESULTS: The total optical density mean VWF level was significantly increased in PWH and higher in ART-naive versus ART-exposed, virally suppressed patients (p < 0.0001). No quantitative difference was demonstrated in the multimer distribution pattern between the groups. CONCLUSIONS: Our findings suggest that there is no difference in multimer distribution between ART-naive and virally suppressed PWH. Due to a small sample size, confirmation in a larger study is required.

High Risk Janus Kinase 2 V617F Allele Burden in a Seven-Year Cohort of Patients with Myeloproliferative Neoplasms.

BACKGROUND: JAK2 V617F is the most common somatic mutation associated with the classical Philadelphia (Ph) chromosome negative myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). JAK2 V617F allele burden may be used for establishing the diagnosis, determining prognosis, and monitoring progression in these diseases. Limited data is available regarding the epidemiology of MPNs in Africa, and there is paucity of data on demographic, laboratory, and clinical features of MPNs in South Africa. This study determined the JAK2 V617F allele burden in a seven-year retrospective cohort of patients diagnosed with MPNs and described the characteristics of these diseases in a South African setting. METHODS: A laboratory database search was performed to identify patients diagnosed with ET, PV or PMF and a positive JAK2 V617F mutation, diagnosed qualitatively on Fluorescence Resonance Energy Transfer (FRET) real-time PCR and melting curve analysis. The allele burden for these patients was measured on archived residual DNA samples using a quantitative allele specific amplification (QUASA) assay. Demographic data and relevant laboratory results at presentation were analyzed. RESULTS: The search identified 87 patients who tested positive for JAK2 V617F mutation and fulfilled the diagnostic criteria for ET, PV or PMF from 2012 to 2018. Median age at diagnosis was 64 years with a male: female ratio of 1.2:1. ET, PV and PMF accounted for 11.5%, 44.8%, and 43.7% of the MPNs, respectively. Median allele burden for ET, PV, and PMF was 24.9%, 71.1%, and 55.8%, respectively. Allele burden was significantly lower in ET compared to PV (p = 0.0003) and PMF (p = 0.0023) and correlated with leukocytosis, neutrophilia, eosinophilia, and low erythrocyte mean cell volume (p < 0.05). CONCLUSIONS: JAK2 V617F-positive MPNs occurred predominantly in older patients with approximately equal gender ratio. ET was the least common MPN and there was a higher proportion of PMF cases than described in studies in Europe and America. Allele burden was also relatively high for all three subtypes of MPNs when compared to other published data, which may predispose to poorer prognosis.

A Rare Prothrombin Gene Mutation C20209T in a South African Patient with Pulmonary Embolism in Pregnancy: a Case Study and Systematic Review.

BACKGROUND: The G202010A prothrombin gene mutation is a documented prothrombotic risk factor in Caucasian patients. Several other mutations have been described within the prothrombin gene, predominantly in non-Caucasians, including the C20209T mutation. The clinical significance of this mutation is uncertain, but it has been associated with thrombotic events and pregnancy complications. METHODS: We describe a 28-year-old black South African woman who presented with pulmonary embolism during pregnancy. She was investigated for underlying prothrombotic biomarkers. RESULTS: Genetic screening for the prothrombin G202010A mutation by real-time polymerase chain reaction and melting curve analysis demonstrated an atypical mutant peak. Sequencing confirmed a variant C20209T prothrombin mutation. CONCLUSIONS: This is the first report of the C20209T mutation in the Southern African population. It remains uncertain whether genetic testing should be offered routinely to non-Caucasian patients in a resource-limited setting.

An Expanded Spectrum of High-Grade B-Cell Non-Hodgkin Lymphomas Involving the Cervicovaginal Region.

The uterine cervix and vaginal regions are infrequently infiltrated by lymphoma. Involvement of these topographic regions may constitute primary disease or more commonly represent a manifestation of systemic lymphomatous disease. Herein, we report an expanded spectrum of high-grade B-cell non-Hodgkin lymphomas comprising plasmablastic lymphoma (with and without plasmacytic differentiation), ALK-positive large B-cell lymphoma, and diffuse large B-cell lymphoma which involved the uterine cervix and/or vagina of 6 patients at initial diagnosis. These tumors clinically mimicked carcinoma and developed predominantly, but not exclusively, in the setting of human immunodeficiency virus infection.

Derangements of immunological proteins in HIV-associated diffuse large B-cell lymphoma: the frequency and prognostic impact.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of B-cells frequently encountered among people living with HIV. Immunological abnormalities are common in immunocompetent individuals with DLBCL, and are often associated with poorer outcomes. Currently, data on derangements of immunological proteins, such as cytokines and acute phase reactants, and their impact on outcomes in HIV-associated DLBCL (HIV-DLBCL) is lacking. This study assessed the levels and prognostic relevance of interleukin (IL)-6, IL-10 and Transforming Growth Factor Beta (TGFß), the acute phase proteins C-reactive protein (CRP) and ferritin; serum free light chains (SFLC) (elevation of which reflects a prolonged pro-inflammatory state); and the activity of the immunosuppressive enzyme Indoleamine 2,3-dioxygenase (IDO)in South African patients with DLBCL. Methods: Seventy-six patients with incident DLBCL were enrolled, and peripheral blood IL-6, IL-10, TGFß, SFLC and IDO-activity measured in selected patients. Additional clinical and laboratory findings (including ferritin and CRP) were recorded from the hospital records. Results: Sixty-one (80.3%) of the included patients were people living with HIV (median CD4-count = 148 cells/ul), and survival rates were poor (12-month survival rate 30.0%). The majority of the immunological proteins, except for TGFß and ferritin, were significantly higher among the people living with HIV. Elevation of IL-6, SFLC and IDO-activity were not associated with survival in HIV-DLBCL, while raised IL-10, CRP, ferritin and TGFß were. On multivariate analysis, immunological proteins associated with survival independently from the International Prognostic Index (IPI) included TGFß, ferritin and IL-10. Conclusion: Derangements of immunological proteins are common in HIV-DLBCL, and have a differential association with survival compared to that reported elsewhere. Elevation of TGFß, IL-10 and ferritin were associated with survival independently from the IPI. In view of the poor survival rates in this cohort, investigation of the directed targeting of these cytokines would be of interest in our setting.

The prognostic impact of monocyte fluorescence, immunosuppressive monocytes and peripheral blood immune cell numbers in HIV-associated Diffuse Large B-cell Lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a high grade non-Hodgkin lymphoma which is common among immunodeficient people. Derangements of peripheral blood immune cells have been described to have a prognostic impact in DLBCL in high income countries, including a monocytosis, the ratios of lymphocytes to both monocytes (L:M) and neutrophils (N:L), as well as the numbers of regulatory T-cells (Tregs) and immunosuppressive monocytes (HLA-DRlow monos). To date, the impact of these variables has not been assessed in the setting of HIV-associated DLBCL (HIV-DLBCL), which is among the most common malignancies seen in people living with HIV. In this study, we assessed these factors in a cohort of South African patients with DLBCL and a high HIV-seropositivity-rate. In addition, we evaluated the prognostic value of monocyte activation (as reflected by monocyte fluorescence (MO-Y) on a Sysmex haematology analyser). This parameter has to date not been assessed in the setting of DLBCL. METHODS: A full blood count and differential count as well as flow cytometry for HLA-DRlow monocyte and Treg enumeration were performed in patients with incident DLBCL referred to the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between November 2019 and May 2022. Additional clinical and laboratory data were recorded from the patient charts and laboratory information system. RESULTS: Seventy-six patients were included, of whom 81.3% were people living with HIV with a median CD4 count of 148 cells/ul. Most patients had advanced stage disease (74.8%) and were predominantly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy (without Rituximab). At a median follow-up period of 19 months, the median survival time was 3.5 months, with a 12-month survival rate of 27.0%. All of the immune-cell-related variables (with the exception of the CD4 count) were similar between the people living with HIV and the HIV-negative individuals. In contrast to previous studies, a high monocyte count, the L:M and increased numbers of HLA-DRlow monocytes were not significantly associated with survival in HIV-DLBCL, while a neutrophilia (>8 x 109/L), the N:L (>6:1), high numbers of Tregs (≥5.17% of CD4s) and lymphopenia (<1.3 x 109/L) were. In addition, increased monocyte fluorescence (MO-Y >115.5) was associated with superior outcomes, which we speculate to reflect a more robust antitumour immune response among individuals with high levels of monocyte activation. On Cox Proportional hazard analysis, immune-cell factors independently associated with survival included a CD4 count <150 cells/ul and a neutrophilia. CONCLUSION: The monocyte count, L:M and the number of HLA-DRlow monos are not strong prognostic indicators in HIV-DLBCL, while a low CD4 count and neutrophilia are. Elevation of the MO-Y shows some promise as a potential biomarker of antitumour immunity; further study in this regard would be of interest.

Validation of the Xpert Breast Cancer STRAT 4 Assay on the GeneXpert instrument to Assess Hormone Receptor, Ki67, and HER2 Gene Expression Status in Breast Cancer Tissue Samples.

Breast cancer is the commonest cause of cancer-related mortality in African females where patients often present later and with advanced disease. Causes for delayed diagnosis include restricted diagnostic access and international controversy on interpretation of ancillary tests like immunohistochemistry (IHC). Fine needle aspirates (FNAC) are an attractive alternative although may have reduced sensitivity. The Xpert Breast Cancer STRAT4 (STRAT4) (CE-IVD*) assay (Cepheid, Sunnyvale) is a semi-quantitative reverse-transcription polymerase chain reaction assay which detects messenger RNA (mRNA) expression in breast samples for estrogen receptor ( ESR1 ), progesterone receptor ( PGR1 ), human epidermal growth factor receptor/Erb-B2 receptor tyrosine kinase 2 (HER2/ ERBB2 ) and the proliferation marker, MKi67 . We assessed the performance of this assay on both formalin-fixed paraffin-embedded (FFPE, n=31) and matched FNAC (n=20) samples from patients presenting with breast cancer to the Johannesburg academic hospitals. IHC and Fluorescent in situ hybridization analysis (performed on HER2-indeterminate samples) was compared with the mRNA expression of the corresponding target genes in FFPE samples, and mRNA expression on FNAC samples was compared with the FFPE results for both mRNA expression and IHC. Concordance between IHC/FISH and Xpert Breast Cancer STRAT4 in FFPE and FNAC samples using the Quick lysis (Q) method (a research-use-only modification of the validated FFPE-lysis method), showed an overall percentage agreement for ESR1 expression of 90.3% and 81.3%, and for PGR1 expression at 86.7% and 81.3% respectively in FFPE and FNAC samples. Concordance was lowest for Ki67 expression, using a binary IHC cutoff for Ki67 positivity at ≥20% staining) at 83.9% and 62.5%, for FFPE and FNAC samples, respectively. This suggests that the STRAT4 assay may be a useful ancillary test in determining HR and Ki67 status in FFPE samples and that use on FNAC samples may be feasible. Future studies should expand the sample numbers and establish locally relevant cutoffs.

Infection and myelodysplasia: A case report of GATA2 deficiency in a South African patient.

Rare diseases often result in delays in diagnosis. It is important to recognize conditions that have features of both inborn errors of immunity and predispose to myeloid neoplasia. Here we report a patient with GATA2 deficiency that presented with disseminated non-tuberculous mycobacterial infection and pancytopenia secondary to myelodysplastic syndrome.

Diffuse Large B-Cell Lymphoma in the Public-Sector of Johannesburg, South Africa, in the Era of Widescale Antiretroviral Therapy Use.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a high-grade non-Hodgkin lymphoma with increased incidence among people living with HIV-infection (PLWH). Although its frequency is reportedly attenuated by antiretroviral therapy (ART), we have previously shown a similar rate of DLBCL in the post-ART era (2017) in Johannesburg, South Africa compared with that observed when ART had only limited availability in the South Africa state-sector (2007). Here, we present a more detailed analysis of DLBCL in the pre-and post-ART eras in Johannesburg. METHODS AND RESULTS: All cases of DLBCL diagnosed in the state-sector hospitals of Johannesburg in 2007 and 2017 were extracted from the laboratory information system, and factors of interest compared. Most (>85%) were observed among PLWH at both time-points; ART-coverage was significantly higher in 2017 compared with 2007, but with failed immunological recovery in 50% of cases. The immunohistochemically-defined cell of origin differed according to HIV-status; the germinal center (GC) and non-GC subtypes predominating in the PLWH and the HIV-negative group, respectively. MYC-gene rearrangement was more common than is reported elsewhere (22.1%), whereas BCL6 and BCL2 gene rearrangements were less so (14.6% and 0%, respectively). Slight improvement in survival was noted in the post-ART era, but remained poor, with bone marrow involvement and albumin levels ≤30 g/L independently associated with mortality. CONCLUSIONS: Although the frequency of DLBCL in Johannesburg has not dropped significantly in the post-ART era, a slight improvement in survival is observed. However, outcomes remain poor, indicating a need for further improvements in care.

Extranodal presentation of a lymphoma with precursor B-cell phenotype and translocation t(8;14) in South Africa.

INTRODUCTION: A rare entity of a B-cell malignancy with precursor B-cell phenotype and concomitant translocation t(8;14) or variant MYC translocation exists. These cases show clinical, pathological and molecular overlap between precursor B-lymphoblastic leukaemia or lymphoma and Burkitt leukaemia or lymphoma (BLL). CASE PRESENTATION: We report a case from February 2019 at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa, of a 9-month-old infant with a predominantly extracranial soft tissue mass showing extradural extension. There was no involvement of the peripheral blood or bone marrow. Fine needle aspiration and Tru-Cut biopsy of the soft tissue scalp mass showed the tumour to be of precursor B-cell phenotype. Contrastingly, an immunophenotypic assessment revealed a high S-phase fraction and raised concern for BLL. This prompted testing for the translocation t(8;14) by fluorescence in-situ hybridisation analysis, which confirmed this aberration. MANAGEMENT AND OUTCOME: Based on the published experience of other centres, the patient was initiated on a BLL protocol. Despite an excellent clinical response, the patient succumbed to neutropenic sepsis six months after diagnosis. CONCLUSION: Leukaemia or lymphoma with translocation t(8;14) or variant MYC translocation and precursor B-cell phenotype is a rare entity with a varied clinical presentation. This poses a challenge for diagnosis and classification and a clinical dilemma for the choice of treatment.

Changing Patterns of Lymphoma in the Antiretroviral Therapy Era in Johannesburg, South Africa.

BACKGROUND: South Africa has a high HIV prevalence, which associates with an increased risk of lymphoma. Antiretroviral therapy (ART) became accessible in 2004, but the program has substantially expanded. Changes in lymphoma patterns are documented in high-income countries after wide-scale ART including declining high-grade B-cell non-Hodgkin lymphomas (HG B-NHLs), particularly diffuse large B-cell lymphoma, and increased Hodgkin lymphoma (HL). There are limited data from Africa. This study aimed to compare HG B-NHL characteristics in the early (2007) and later (2017) ART era. METHODS: All incident lymphomas at the National Health Laboratory Service, Johannesburg, were identified using the laboratory information system, and data were collected for each patient. RESULTS: The total number of lymphoma cases increased from 397 (2007) to 582 (2017). This was associated with improved lymphoma classification and patient referral for oncological care. HG B-NHL remained the most diagnosed lymphoma subtype in 2017 comprising 70% of HIV-associated lymphomas, followed by HL (24%). Diffuse large B-cell lymphoma comprised 65% of all HG B-NHLs and 45% of all lymphomas in people with HIV in 2017. Significantly more patients were on ART in 2017, with improvements in virological control documented. Despite this, 47.6% of patients were not virologically suppressed, and 37.5% of patients were ART-naive at time of diagnosis in 2017. Immunological reconstitution was suboptimal, which may reflect late initiation of ART. CONCLUSION: Public health initiatives to initiate ART as early as possible and to retain patients in ART programs may assist in decreasing the number of HIV-associated lymphomas in our setting.

Preparing for the next pandemic: Lessons from rapid scale-up of SARS-CoV-2 testing in a South African high-throughput automated HIV molecular laboratory.

Africa's readiness to respond to the SARS-COV-2 pandemic was tested due to reliance on rapid turn-around-time of polymerase chain reaction results for clinical management, isolation and quarantine decisions. The NHLS HIV Molecular Laboratory in Johannesburg, South Africa, is one of the largest automated HIV molecular laboratories worldwide. Despite its extensive molecular capacity and experience in managing high volumes acquired from a large HIV program, significant challenges were encountered during its rapid transition to large scale SARS-CoV-2 testing. We describe the strategies employed to manage these challenges that resulted in a 30% improvement in SARS-CoV-2 test turn-around-time during the first wave peak during which approximately 25000 samples were tested per month, and further improvement during the second wave peak, with 81% within targeted turn-around-time.

Brief Report: HIV-Associated Hodgkin Lymphoma Involving the Bone Marrow Identifies a Very High-Risk Subpopulation in the Era of Widescale Antiretroviral Therapy Use in Johannesburg, South Africa.

BACKGROUND: The incidence of HIV-associated Hodgkin lymphoma (HIV-HL) has not dropped in the era of widespread antiretroviral therapy (ART), and there have reportedly been shifts in the most prevalent variants encountered. In this study, factors of interest in cases of HIV-HL diagnosed before and after the widespread availability of ART in Johannesburg, South Africa, were compared. METHODS: All cases of HIV-HL diagnosed in 2007 and 2017 were extracted from the laboratory information system, and pertinent factors compared. RESULTS: The number of cases of HL increased significantly over the period assessed, but without a clear increase in the incidence of HIV-HL. As has been reported previously, the proportion of HIV-HL subclassified as the Nodular Sclerosis and Mixed Cellularity subtypes increased and decreased respectively over the period. The number of unclassifiable cases also increased significantly largely because of more frequent diagnosis in bone marrow (BM). BM involvement was highly prevalent at both timepoints (51.7% in 2007 vs 66.2% in 2017; P = 0.18), but was more frequently associated with multiple cytopenias in 2017. Despite significant ART upscaling, the median CD4 count was significantly lower in 2017 (242.5 cells/µL in 2007 vs 85.5 in 2017; P = 0.002). This particularly affected patients with BM involvement, and the median survival time was significantly shorter among BM+ patients diagnosed in 2017 as compared to those diagnosed in 2007. Notably, 40.8% of the patients with BM involvement diagnosed in 2017 died before the diagnosis was established. CONCLUSION: HIV-HL with BM involvement identifies a very high-risk subpopulation in the post-ART era.

Hematologic malignancies in South Africa 2000-2006: analysis of data reported to the National Cancer Registry.

Little is known about the incidence patterns of hematologic malignancies in Sub-Saharan Africa, including South Africa. We estimated incidence rates of pathology-confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and 2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender-specific age-standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20-50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set-up of the NCR (pathology-based) could lead to some degree of under-ascertainment in all groups. This is the first country-wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer-related health care.

Hepatosplenic T-cell lymphoma: A case series.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of Non-Hodgkin Lymphoma (NHL), grouped under the mature or peripheral T-cell lymphomas. It is characterised by extranodal infiltration and proliferation of malignant T-cells within the sinusoids of the liver, sinuses and red pulp of the spleen, and the bone marrow. The tumour cells express CD2 and CD3, but are CD4, CD5 and CD8 negative and express a clonally restricted gamma-delta (or less commonly alpha-beta) T-cell receptor. The disease has an aggressive clinical course associated with a poor prognosis. We highlight and report three patients from South Africa with HSTCL, all of whom had hepatosplenomegaly and cytopaenias, and despite being HIV seronegative and immunocompetent, had a poor outcome, with a mean survival of 7.5 months in the two evaluable patients. This rare entity has not previously been reported from South Africa and as yet needs to be adequately characterised in a population where lymphoma is the most common haematological malignancy in adults, and where approximately two thirds of the adult lymphoma population are HIV seropositive.

Immature platelet fraction levels in a variety of bone marrow pathologies in South African HIV-positive patients with thrombocytopenia.

OBJECTIVES: Thrombocytopenia is common in HIV-infected individuals and often requires a diagnostic bone marrow examination. Interpretation may, however, be limited due to the multifactorial nature of HIV-associated thrombocytopenia and the difficulty in assessing megakaryocyte function morphologically. The immature platelet fraction (IPF) is a parameter which reportedly reflects megakaryocyte activity, with an IPF >7.7% suggesting increased platelet production. The aim of this study was to correlate the IPF with the bone marrow findings as well as other clinical variables of interest in South African patients with HIV-associated thrombocytopenia. METHODS: Seventy-eight HIV-positive patients with thrombocytopenia were enrolled from the Charlotte Maxeke Johannesburg Academic Hospital. The IPF levels were measured using a Sysmex XE-5000 haematology analyzer and were correlated with bone marrow and other findings. RESULTS: The median IPF was 7.6%, ranging from 1.3 to 44%. It was raised in 78% of patients with immune thrombocytopenia (ITP) (median = 16.3%) and low in 79% of patients with hypocellular marrow (median = 6.5%). Surprisingly, it was highly variable among patients with malignant marrow infiltration and mycobacterial infection of the bone marrow (BMTB) (median = 8.4 and 7.1%, respectively). Multivariate linear regression analysis confirmed a significant independent inverse relationship between the IPF and hypocellular marrow (P < 0.0001), a marginally significant positive association with ITP (P = 0.059), and the absence of any relationship with malignant infiltration or BMTB. The IPF had a significant inverse association with the platelet count (P = 0.0006), but was unrelated to the CD4 count and exposure to anti-retroviral therapy. Unexpectedly, it showed a significant positive association with the HIV viral load (P = 0.005). We speculate this to reflect increased megakaryocyte activity in compensation for accelerated platelet clearance due to HIV-driven platelet activation. CONCLUSION: This study investigates the role of the IPF in HIV-associated thrombocytopenia, and emphasizes the limitations of morphological analysis in determining megakaryocyte function.

Changing pattern of lymphoma subgroups at a tertiary academic complex in a high-prevalence HIV setting: a South African perspective.

BACKGROUND: HIV infection has been associated with an increased risk of non-Hodgkin lymphoma, particularly in the first world. Despite the high burden of HIV infection in sub-Saharan regions, published data on HIV and malignancies are sparse from these areas. MATERIALS AND METHODS: We recently published data on lymphomas diagnosed from January 2004 to December 2006, at a single center in Johannesburg, to serve as a baseline for long-term comparison during the period of highly active antiretroviral therapy rollout. We report a retrospective analysis of the follow-up data collected from January 2007 to December 2009 at the Johannesburg academic hospital complex (Gauteng, South Africa). RESULTS: There were 2225 new diagnoses of lymphoproliferative disorders made during 2007-2009 as compared with 1897 cases diagnosed during 2004-2006. A significant increase in both high-grade B-cell lymphomas and Hodgkin lymphoma was documented during 2007-2009. This was associated with a statistically significant increase in HIV prevalence in those tested (from 44.3% in 2004-2006 to 62.0% in 2007-2009). HIV-positive patients presented at a statistically significantly younger median age and showed a relative overrepresentation of females when compared with HIV-negative patients. HIV-positive patients were diagnosed at later stages of HIV infection when compared with patients in the first world. CONCLUSIONS: The pattern of lymphoma subtypes and the demographics of the patients diagnosed have altered in association with significantly increased HIV prevalence. These changes have important public health implications. In particular, scale-up and earlier access to highly active antiretroviral therapy is essential with continued monitoring as access to therapy improves.

Characterization of Lymphomas in a high prevalence HIV setting.

BACKGROUND: HIV infection has been associated with an increased risk of malignancy, both AIDS defining and non-AIDS defining. METHODS: This study presents a detailed pathological description of newly diagnosed lymphomas in Johannesburg, South Africa (January 2004 and December 2006). The review coincides with introduction of combination antiretroviral therapy. RESULTS: One thousand eight hundred and ninety-seven new lymphoproliferative disorders were referred to the Charlotte Maxeke Johannesburg Academic Hospital. B-cell non-Hodgkin lymphoma accounted for 83%, T-cell non-Hodgkin lymphoma 3.5%, and Hodgkin lymphoma 7% of cases. The overall prevalence of HIV infection was 37% (n = 709). Diffuse large B-cell lymphoma (21%; n = 401) was the most common lymphoma. HIV prevalence ranged from an absence in follicular or mantle cell lymphoma to a low prevalence in diseases like small lymphocytic lymphoma/chronic lymphocytic leukemia (4%) and pre-B/common ALL (5%) to a high prevalence in diffuse large B-cell lymphoma (80%), Burkitt lymphoma/leukemia (86%), and primary effusion lymphoma (100%). CONCLUSIONS: This study provides a baseline for monitoring the impact of HIV and management thereof on lymphoma trends. The high prevalence of HIV in certain lymphoma categories emphasizes the need for capacity to diagnose and manage dual conditions. This study highlights the need for strengthening of cancer registries within South Africa and the region.