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Introduction: In acquired hemophilia A (AHA), the body produces auto-antibodies against Factor VIII. Although AHA is rare, with an incidence of 1.5 patients/1 million population/year, there is a strong association with human immunodeficiency virus (HIV) infection. The accurate interpretation of screening coagulation tests is critical to identify patients with AHA, as the mortality rate secondary to bleeding is high. Methods: This was a retrospective case series which included all newly diagnosed AHA patients that were referred to Hemophilia care unit at King Edward VIII Hospital, Durban, South Africa from January 2011 to December 2021. The clinical presentation and laboratory results were documented. Results: Five patients were included in this case series. All patients were females aged between 28 and 64 years of age and they were HIV seropositive. They presented with spontaneous cutaneous and intramuscular bleeding. Four patients were virologically suppressed on anti-retroviral therapy, and no patient had a family history of congenital bleeding diathesis. Laboratory investigations confirmed AHA with high Factor VIII inhibitor titers, which ranged from 41 to 900 Bethesda Units (BU). All patients were managed with bypassing agents and oral corticosteroids. The monitoring of patients after the initiation of treatment was difficult as they all defaulted treatment. Conclusion: In view of the prevalence of HIV in sub-Saharan Africa, there is a possibility that AHA is under-diagnosed in our setting. The clinician and the laboratory have a combined critical role in identifying patients with AHA as the investigation of a prolonged APTT is mandatory. There are challenges in managing AHA patients in a resource-constrained setting.

Background: Automated haematology analysers such as the Sysmex XN-3000 (Sysmex Corporation, Kobe, Japan) utilise white blood cell (WBC) flags to identify quantitative and qualitative abnormalities. Owing to clinical and biological factors, the sensitivity and specificity of the flags vary when compared to microscopy, the gold-standard method for assessing peripheral blood smear (PBS) morphology. Objective: This study assessed the performance of the Sysmex XN-3000 haematology analyser in comparison to PBS microscopy for the detection of WBC abnormalities. Methods: We collected 250 random full blood count samples from the haematology laboratory at Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, from March 2022 to April 2022. The performance of the automated WBC flags of the Sysmex XN-3000 was assessed in comparison to PBS microscopy, and the impact of established clinical variables on the performance of the flags was determined. Results: The sensitivity of the ‘blast’ flag was 96.3%, and the specificity was 84.9%. The efficiency of the flag was adversely impacted by low white cell counts ( 1.5 × 109/L; p 0.001), chemotherapy (p = 0.002), malignancy (p = 0.02), and infection (p = 0.02). The ‘abnormal lymphocyte’ flag demonstrated a sensitivity of 90% and a specificity of 96.2%, and its performance was adversely impacted by chemotherapy exposure (p = 0.03). Three cases (1.2%) erroneously flagged as ‘monocytosis’ demonstrated blasts on microscopy. Conclusion: In our setting, PBS microscopy remains necessary to confirm blasts, abnormal lymphocytes, and monocytosis in patients with malignancy, current chemotherapy exposure, low white cell counts, and infection. What this study adds: This study adds evidence that PBS morphology remains the gold standard for confirming WBC abnormalities in patients with a history of malignancy, chemotherapy, and leucopenia.

Abstract Background Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that harbors the Philadelphia chromosome. Tyrosine kinase inhibitor (TKI) therapy has dramatically improved the survival of patients with CML. Nevertheless, 20%–40% of CML patients require changes in TKI therapy due to intolerance or drug resistance. A total of 30%–60% of resistant cases result from kinase domain (KD) mutations. There is currently no published data on CML KD mutations in South Africa. Methods This retrospective, descriptive study collected data from 206 CML patients attending the King Edward Hospital Hematology clinic. Patient‐based and mutation‐based factors were analyzed using descriptive statistical analysis and Kaplan–Meier curves for survival analysis. Results KD mutations were detected in 29.1% (n = 60 of 206). A total of 40 different KD mutations were detected, with unknown responses to TKI therapy in 65% (n = 26 of 40). A total of 57.7% (n = 15 of 26) of mutations with an unknown response, showed a response to specific TKIs in our study. Four patients had A399T mutations, of which two showed good responses to Nilotinib. Patients with I293N and V280M mutations showed good responses to Imatinib. G250E was most frequently detected. Despite M351T being one of six most commonly reported KD mutations globally, this mutation was not detected in our patient cohort. A total of 20.9% (n = 43 of 206) human immunodeficiency virus (HIV) positive patients were identified, of which 25.6% (n = 11 of 43) had KD mutations. HIV status showed no significant effect on mutational status or overall survival. Conclusion The predicted response to TKI therapy was unknown in more than half of the KD mutations detected in our patient population. Additionally, eight patients with mutations with known responses to TKIs showed responses discordant to that expected. HIV status and KD mutations had no statistically significant effect on overall survival. Although some data were comparable to international publications, few notable differences warrant further investigation.

Abstract Background Due to the high prevalence of HIV, HIV-associated lymphoma (HAL) is a common malignancy in South Africa. However, there is a paucity of literature on HAL from this region. The objective of this study was to profile the clinical characteristics and outcome of CD20-positive HAL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), with or without rituximab (R), from a single center in KwaZulu -Natal, South Africa. Methods Retrospective chart review of adult patients treated from 2006 to 2018 for HIV-associated CD20-positive lymphoma. The clinical characteristics, complete response (CR), and 2-year overall survival (OS) are described. Results The analysis included 102 patients, 54% females, median age of 39 years, and median CD4 cell count of 196 cells/μL. Bone marrow involvement was noted in 5%. Eighty-six percent of the cohort received concomitant antiretroviral therapy and chemotherapy, 76% of the CHOP group, and 92% of the R-CHOP group. Overall, a CR was seen in 55% (95% CI 45%; 65%), with a 2-year OS of 59% (95% CI 50%, 69%). A CR was attained in 46% on CHOP and 64% on R-CHOP, with a 2-year disease-free survival (DFS) for CHOP of 42% and 50% for R-CHOP. Conclusion Although the clinical characteristics and laboratory findings are similar to other higher-income cohorts, there was a difference in gender and incidence of marrow involvement. The low incidence of marrow involvement has prompted more routine use of immunohistochemistry and flow cytometry in staging marrows of HAL locally. Further randomized studies are required for the establishment of locally validated, cost-effective treatment guidelines.

ObjectivesTo profile the outcome of multiple myeloma (MM) patients treated at a South African tertiary hospital in KwaZulu-Natal (KZN) and to compare MM in HIV-negative patients and MM in people living with HIV (PLWH).MethodsA retrospective analysis of patients with MM was conducted over 5 years (2015-2020). Patient demographics, presenting complaints, symptom duration, disease stage, molecular profile, treatment, and survival data were captured. Statistical analysis was conducted using R Statistical software of the R Core Team, 2020, version 3.6.3.Results135 patients; 79% (n = 106) HIV-negative and 21% (n = 29) PLWH were investigated. 54% (n = 74) females and 57% (n = 76) 51-70-year-olds. The 40-50-year-old patient group had a significantly higher proportion of PLWH (p = 0.032). Pathological fractures were the commonest presenting complaint, 47% (n = 57 and 49% (n = 49) had International Staging System, stage III disease. Fluorescent in-situ hybridization (FISH) MM profiling was completed in 58% (n = 78). Positivity for del 11q22 was found in 23.7% (n = 14) with significantly more HIV-negative patients having the mutation (p = 0.027). Overall, 42.2% (n = 57) achieved 2-year overall survival (OS). There were no significant differences in treatment (p = 0.926) and 2-year survival outcome (p = 0.792) between the two groups.ConclusionThe incidence of HIV in newly diagnosed MM patients in KZN was increasing. KZN patient profile differed from other reports by showing female predominance but was similar in advanced-stage presentation and bone fracture predominance. Statistically significant differences between the HIV-negative patients and PLWH were observed in age distribution and mutational landscape. Further studies are required in this area.

Introduction. Chronic myeloid leukaemia (CML) management has evolved from a disease once considered to be incurable just over 2 decades ago to that of one of a “functional cure” as defined by the sustained molecular response on stopping tyrosine kinase inhibitor(TKI) therapy. The next goal of CML management has been treatment-free remission (TFR). The past 4 years have seen much international data on TFR attempts in CML in clinical practice. However, Africa as a continent has lagged behind the rest of the world, in keeping up with the latest trends in CML management, and so this study aims to address this gap by assessing the outcome of TFR in CML in a single centre in South Africa (SA). Methods. We conducted a retrospective cohort study in 12 CML patients in the chronic phase to assess the success of TKI discontinuation. The patients were treated in King Edward VIII Hospital (KEH), a tertiary, academic hospital in KwaZulu-Natal, South Africa, and the study period was from June 2020 to May 2022. Patients included had to have been on TKI therapy for a minimum of 5 years and achieved a deep molecular response (DMR) for a minimum period of 3 years. Results. The overall TFR cohort showed a success rate of 75% at a median follow-up of 12 months. All patients who failed TFR, defined as a loss of major molecular remission (MMR), failed within 6 months of stopping TKI therapy. All patients who failed TFR regained DMR after retreatment with TKI, with no disease progression reported. The only factor influencing the success of TFR was the total period of TKI therapy. Conclusion. Despite our study having a small cohort of patients, this study demonstrated that TFR in CML is an attainable goal, even in a resource-limited setting.

Background: The recommendation for coagulation blood samples is to centrifuge at 4000 revolutions per minute (rpm) for 15 min to produce platelet-poor plasma before analysis. Rapid centrifugation, defined as centrifuging samples at higher speeds for shorter durations, could potentially reduce turn-around times (TAT), provided sample integrity is maintained. Objective: This study assessed the impact of rapid centrifugation on routine coagulation assay results. Methods: Blood samples were collected from volunteers at Inkosi Albert Luthuli Central Hospital and King Edward VIII Hospital, Durban, KwaZulu-Natal, South Africa, from September to November 2021. Samples were centrifuged using Method A, the current standard (4000 rpm/15 min), Method B (4000 rpm/10 min), Method C (5000 rpm/10 min) and Method D (5000 rpm/5 min). Platelet count, prothrombin time, activated partial thromboplastin time, thrombin time (TT), fibrinogen and D-dimer levels were analysed and results from Methods B, C and D compared to reference Method A. Results: Platelet-poor plasma was obtained from all samples (n = 60) using Methods A and B, and from 33/60 (55%) samples using Methods C and D. Differences between Method A and Methods C and D for normal prothrombin time, normal D-dimer and abnormal TT results were statistically significant. Prothrombin time results correlated strongly across all methods, while TT and D-dimer results correlated poorly. Activated partial thromboplastin time and fibrinogen results showed no significant differences across all methods. Conclusion: Rapid centrifugation at 4000 rpm/10 min (Method B) showed results consistent with the reference method. This method could potentially reduce the overall TAT for routine coagulation assays.

Background: Paroxysmal nocturnal haemoglobinuria (PNH) clones in children are rare but commonly associated with aplastic anaemia (AA) and myelodysplasia. Objective: This study aimed to determine the prevalence of PNH clones in paediatric patients with idiopathic AA, identify differences in clinical and laboratory features and outcomes, and determine the impact of clone size on clinical presentation. Methods: Patients with confirmed idiopathic AA who were tested for PNH between September 2013 and January 2018 at the Inkosi Albert Luthuli Central Hospital, Durban, KwaZulu-Natal, South Africa, were included. PNH clones were detected in neutrophils and monocytes by flow cytometry using fluorescent aerolysin, CD24, CD66b and CD14. Results: Twenty-nine children with AA were identified and 11 were excluded. Ten patients (10/18, 55.6%) had PNH clones ranging from 0.11% to 24%. Compared to the PNH-negative group, these children were older (median: 10 years vs 4 years, p = 0.02) and had significantly lower total white cell counts (median 1.7 × 109/L vs 3.2 × 109/L; p = 0.04). There was no difference in median absolute neutrophil count or haemoglobin concentration. Four patients in each group received immunosuppressive therapy (IST). At six months, all four patients with PNH clones had responded, compared to one in the PNH-negative group. Conclusion: More than half of children with AA had a PNH clone. The size of the clone did not impact clinical severity; however, IST use may positively impact prognosis. We recommend early initiation of IST in patients with AA to avoid delays associated with human leukocyte antigen typing.

ObjectiveTo describe 4-year survival outcomes and assess the value of established and additional relevant variables to predict complete response (CR), four-year progression-free survival (PFS) and overall survival (OS) of CD20 positive AIDS-Related Lymphoma (ARL) treated with standard combination chemotherapy.MethodWe performed a retrospective review of patients diagnosed with CD20 positive ARL between 2006 and 2016. All patients over 12 years of age who received at least one cycle of combination chemotherapy with curative intent were included in the analysis. Variables assessed included the International Prognostic Index (IPI), age-adjusted-IPI, age, gender, B symptoms, extent of disease, functional performance status, CD4 cell count, viral load, concurrent ART with chemotherapy, rituximab inclusion, and number of chemotherapy cycles used. Kaplan-Meier survival curves for OS and PFS at 4 years were compared for IPI and aaIPI using the log-rank test. A Cox proportional hazards model was used to investigate the effects of prognostic variables for patients achieving OS and PFS at 4 years and logistic regression for patients achieving CR.ResultsA total of 102 patients were included in the analysis. At year four of follow-up, the OS was 50% (n = 51) and PFS was 43% (n = 44). Attaining a CR and male gender were significantly associated with improved 4-year OS (pConclusionThis study is a first from a high prevalence HIV area in KwaZulu-Natal, South Africa, and confirms the utility of the internationally accepted prognostic scoring systems in predicting survival in CD20 positive ARL in the local population.

Background: The International Myeloma Working Group and College of American Pathologists recommend a 24-h urine collection to determine the Bence Jones protein (BJP) excretion level for monitoring treatment response in patients with multiple myeloma (MM). There are several issues related to sample collection and the method is prone to inaccuracy. Objective: This study compared measured 24-h to random urine collections for the quantitation of BJP in a South African population. Methods: Sixty-six patients with MM submitted random urine samples with their routine 24-h urine collection from April 2016 – March 2018. Measured 24-h urine BJP was compared to two estimated 24-h BJP excretions calculated as follows: Estimation 1 (E1): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 10. Estimation 2 (E2): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 15 mg/kg for women or × 20 mg/kg for men. Results: Correlation of estimation equations E1 and E2 to the measured 24-h urine BJP was 0.893. Patients showed no difference in classification of treatment response using either the E1 or E2 estimation equations when compared to the measured 24-h urine BJP results. Conclusion: This study demonstrates that the estimated 24-h BJP shows a high degree of correlation with the measured 24-h BJP and can likely be used to monitor treatment response in South African patients with MM.

ackground:Minimal residual disease (MRD) detection has been shown to be the best prognostic factor in B-acute lymphoblastic leukaemia (B-ALL). Multicolour flow cytometry (FCM) and specific molecular aberrations (MOL) are the classic techniques used to assess MRD. The former is faster and less costly. Aim: This study compares morphology and FCM to MOL in detecting MRD. Setting: The study was conducted at Inkosi Albert Luthuli Central Hospital (IALCH). Methods: A retrospective review of children with B-ALL managed at IALCH from January 2013 to January 2018 was conducted. Multicolour flow cytometry was performed using Euroflow® panels. Molecular aberrations looked at common cytogenetic markers. Presentation and post-induction morphology (May–Grunwald Giemsa stain), FCM and MOL data for MRD were analysed. Results: Eleven patients were excluded (6-demised, 5-incomplete records), leaving 64 to be analysed (54% female, median age 5 years). Five post-induction aspirates were unsuitable but the rest (92%) were in morphological remission. At diagnosis and post-induction, 62 (95%) and 61 (94%) children, respectively, had FCM performed. A positive MOL result was found in 39 (60%) patients. MOL turn-around times (TATs) averaged 14 days compared with those of FCM’s average of 3 days. MRD was found in 9 patients (FCM) and 7 patients (MOL). Of these patients, 4 had a good correlation between the two and 2 patients with negative FCM had positive MOL MRD post-induction. Conclusion: Morphology is insensitive in MRD assessment. FCM correlated well with molecular MRD and has the shortest turn-around time. FCM has major benefit in the 40% of patients with negative MOL. It can also be safely used to guide treatment escalation in those patients awaiting molecular results.