Impact of Binet Staging versus Tumour Bulk on Treatment Outcome in Chronic Lymphocytic Leukaemia.

BACKGROUND: Most of the predictive tools put up to prognosticate treatment outcomes in patients with chronic lymphocytic leukaemia (CLL) are not easily available and affordable in our resource-constrained environment. AIM: The aim of this study was to evaluate the impact of staging and some tumour bulk on treatment outcomes of persons with CLL, Enugu, Nigeria. PATIENTS AND METHODS: This is a 10-year review of the CLL data from the haemato-oncology unit of a Nigerian tertiary hospital to evaluate the impact of staging and tumour bulk indicators. Data were retrieved from the case notes of 102 patients with CLL receiving care at the facility. Data of interest include basic demographic variables, clinical features including spleen size and disease staging and blood counts. Statistical analysis was done using SPSS version 22. RESULTS: The median absolute lymphocyte count (ALC) was 108.05 (confidence interval [CI] = 50.8-201.3, interquartile range [IQR] = 124.4) ×109/L, and duration of survival for the study cohort was 5.5 (CI = 3.5-31.9, IQR = 27) months. Majority (69, 79.3%) were in Stage C. The Binet stage showed a significant association with the ALC (r = 0.338; P = 0.002) but not with spleen size (r = 0.198; P = 0.056). The duration of survival only showed a significant inverse relationship with the ALC (r = 0.35, P = 0.006) but with neither the Binet stage (r = 0.103, P = 0.431) nor spleen size (r = 0.184, P = 0.116). CONCLUSION: In CLL patients, ALC at presentation correlates with the duration of survival. We recommend that the ALC at presentation be used as a prognostic marker in our clime.

Cerebral artery conditional blood velocity in sickle cell disease: a multicentre study and evidence for active treatment.

OBJECTIVE: To obtain multicentre data on the prevalence of normal, high or conditional (intermediate) blood velocity in the cerebral arteries among children with sickle cell disease (SCD) in Nigeria. DESIGN: A prospective observational study in five tertiary healthcare institutions. By transcranial Doppler (TCD) ultrasonography, cerebral artery peak systolic blood velocity (PSV) was determined in 193 children with SCD and time averaged mean of the maximum blood velocity (TAMMV) in a different cohort of 115 children. This design was to make the findings relevant to hospitals with TCD equipment that measure either PSV or TAMMV. SETTING: Nigeria. PARTICIPANTS: 308 children (126 girls, 182 boys; age 2-16 years). MAIN OUTCOME MEASURES: Percentage of children with SCD who have normal, high or intermediate (often termed conditional) PSV or TAMMV. RESULTS: In the cohort of 193 children, PSV was normal in 150 (77.7%), high in 7 (3.6%) and conditional in 36 (18.7%). In the cohort of 115 children, TAMMV was normal in 96 (84%), high in 7 (6%) and conditional in 12 (10%). There were no significant differences in gender or age distribution between the PSV and TAMMV cohorts. Altogether, cerebral artery blood velocity was normal in 246/308 children (80%), high in 14 (4.5%) and conditional in 48 (15.5%). CONCLUSION: Since conditional blood velocity in cerebral arteries can progress to high values and predispose to stroke, the proportion of children with SCD who are affected (15.5%) raises the question of whether regular monitoring and proactive intervention ought to be the standard of care.

Plasma concentration of fucosyltransferase 7 is not associated with the number of clinically overt vaso-occlusive events in sickle cell disease.

Objective: To determine if the number of vaso-occlusive events in SCD relates to plasma concentration of fucosyltransferase 7 (FUT7), which catalyses the synthesis of selectin ligands. Design: A prospective, analytical study. Setting: Haematology and Chemical Pathology Departments of tertiary healthcare centres. Participants: Steady state HbSS individuals aged 13-45 years, 20 had 3 or more vaso-occlusive crises that required hospital admission in the previous year (with or without complications of SCD); 17 other HbSS persons had 0-1 vaso-occlusive crisis that required hospital admission in the previous year and no disease complications. Intervention: Steady-state plasma concentrations of FUT7 measured by ELISA were compared between SCD patients who had one vaso-occlusive crisis requiring hospital treatment in the previous year but no disease complications and those who had >3 crises with or without complications. Main Outcome Measures: Plasma level of FUT7and the number of vaso-occlusive events in each HbSS patient. Results: Mean + standard deviation plasma concentration of FUT7 was 8.6 + 2.7 ng/ml in patients with >3 vasoocclusive crises in the previous year and 7.3 + 1.7 ng/ml in those with 0-1 crisis and no complications; independent sample t-test, p > 0.05, not significantly different. Conclusion: Plasma concentration of fucosyltransferase7 is not associated with the number of vaso-occlusive events in sickle cell disease. Funding: None declared.

Prevalence of venous thromboembolism and its associations in a large racially homogenous population of sickle cell disease patients.

To determine the prevalence of venous thromboembolism (VTE) among adult sickle cell disease (SCD) patients in Nigeria. METHODS: This was a multicentre retrospective study in which the medical records of adult SCD patients were reviewed. Information on demographics, steady-state haemogram, clinical phenotypes, duration of follow-up, history of VTE including risk factors and management was collected. RESULTS: Of the 509 SCD patients with a median (IQR) duration of follow-up of 2 years, 10 (2.0%) had VTE (9 DVT and 1 PE). Their median (IQR) age was 27 (22.8-30.3) years. Identifiable risk factors for VTE included positive family history (2, 20%) surgery, splenectomy, paraplegia and cancer (1, 10% each). No risk factor was identifiable in four persons. VTE had no significant association with age and gender. VTE was significantly associated with the following events: acute chest syndrome [p = .002, odds ratio (OR) 8, 95% CI 2.2-28.9], osteonecrosis [p = .012, OR 5.24, 95% CI, 1.45-18.91] and vaso-occlusive crisis [p = .035]. Also significantly associated with VTE were pulmonary hypertension [p = .001, OR 23.3, 95%CI 5.18-105.06] and stroke [p = .032, OR 9.35, 95%CI 0.87-53.25]. CONCLUSION: The prevalence of VTE among SCD patients in Nigeria is low. It is significantly associated with vaso-occlusive crisis, pulmonary hypertension and stroke.

Variations and characteristics of the various clinical phenotypes in a cohort of Nigerian sickle cell patients.

BACKGROUND: Sickle cell anaemia affects about 4 million people across the globe, making it an inherited disorder of public health importance. Red cell lysis consequent upon haemoglobin crystallization and repeated sickling leads to anaemia and a baseline strain on haemopoiesis. Vaso-occlusion and haemolysis underlies majority of the chronic complications of sickle cell. We evaluated the clinical and laboratory features observed across the various clinical phenotypes in adult sickle cell disease patients. METHODS: Steady state data collected prospectively in a cohort of adult sickle cell disease patients as out-patients between July 2010 and July 2020. The information included epidemiological, clinical and laboratory data. RESULTS: About 270 patients were captured in this study (165 males and 105 females). Their ages ranged from 16 to 55 years, with a median age of 25 years. Sixty-eight had leg ulcers, 43 of the males had priapism (erectile dysfunction in 8), 42 had AVN, 31 had nephropathy, 23 had osteomyelitis, 15 had osteoarthritis, 12 had cholelithiasis, 10 had stroke or other neurological impairment, 5 had pulmonary hypertension, while 23 had other complications. Frequency of crisis ranged from 0 to >10/year median of 2. Of the 219 recorded, 148 of the patients had been transfused in the past, while 71 had not. CONCLUSION: The prevalence of SLU, AVN, priapism, nephropathy and the other complications of SCD show some variations from other studies. This variation in the clinical parameters across different clinical phenotypes indicates an interplay between age, genetic and environmental factors.

Seroprevalence of human T-cell lymphoma/leukemia virus type-1 (HTLV-1) antibodies among blood donors at Enugu, Nigeria.

BACKGROUND: Human T-cell lymphotrophic/leukemia virus (HTLV-1) is a retrovirus implicated in transfusion-transmitted infection. OBJECTIVE: The objective of this study was to determine the seroprevalence of HTLV-1 antibodies among blood donors at the University of Nigeria Teaching Hospital, Enugu, Eastern Nigeria. METHODS: A cross-sectional study was carried out on consented participants over 4 months. A total of 300 blood donors were recruited consecutively from the blood bank. The serum of the collected 5 mL of blood obtained from each participant was stored at -20°C until required for analysis. The serum samples were then analyzed for antibodies to HTLV-1 using a one-step incubation double-antigen sandwich ELISA (enzyme-linked immunosorbent assay) kit. Participants' demographic characteristics and degree of exposure to the risk factors associated with HTLV-1 infection were captured using a questionnaire. Statistical analysis of results was done using SPSS version 17. RESULTS: Of the 300 blood donors, 288 (96%) were male, while 12 (4%) were female. The average age of the blood donors was 26.85±8.52 years. The age group with the highest representation among the blood donors were those aged between 21 and 25 years. Only 22.3% of the blood donors were above 30 years. None of the 300 screened blood donors tested positive to HTLV-1 antibodies. Hence, the seroprevalence of HTLV-1 infection among blood donors was 0%. Of the blood donors, 5% had history of previous sexually transmitted disease, while 34.7% used condoms during sexual intercourse. CONCLUSION: The seroprevalence obtained in this study cannot statistically support the justification of routine screening of blood donors for HTLV-1 infection. More prospective and multicentered studies are required to determine the infectivity of HTLV-1 in blood donors in Nigeria.

Stroke prevalence amongst sickle cell disease patients in Nigeria: a multi-centre study.

BACKGROUND: Stroke is a life-changing, debilitating complication of sickle cell disease (SCD). Previous studies had recorded high stroke prevalence amongst this group of patients. Nigeria has a large population of people affected by this condition and this study aims to assess the stroke prevalence in this large population. METHODOLOGY: Stroke prevalence data from 14 physicians working in 11 tertiary health centres across the country was collated by doctors using the sickle cell registers and patient case notes. This data was then collated and used to obtain the overall stroke prevalence in adult and children. RESULTS: The stroke prevalence in sickle cell disease patients in Nigeria was observed to be 12.4 per 1000 patients. Prevalence in the adult patients was 17.7 per 1000 patients and 7.4 per 1000 patients in children. Twenty three percent of the affected patients had more than stroke episode. CONCLUSION: The stroke prevalence in Nigeria is lower than previously recorded rates and further studies will be required to investigate other factors which may play a role.

Seroprevalence and correlates of human T-cell lymphoma/leukemia virus type 1 antibodies among pregnant women at the University of Nigeria Teaching Hospital, Enugu, Nigeria.

BACKGROUND: Human T-cell lymphoma/leukemia virus (HTLV)-1 is a retrovirus transmitted vertically from mother to child parenterally and sexually by infected lymphocytes. OBJECTIVE: The objective of this study was to determine the seroprevalence of HTLV-1 antibodies and associated risk factors for HTLV-1 infection among pregnant women in University of Nigeria Teaching Hospital, Enugu, southeast Nigeria. MATERIALS AND METHODS: A cross-sectional study was carried out from July to October 2010. Two hundred pregnant women were recruited consecutively from the antenatal clinic. Five milliliters of blood was collected from each of the participants into a plain sterile bottle and allowed to clot. The serum obtained was stored at -20°C until required for analysis. The serum samples were then analyzed for antibodies to HTLV-1 using a one-step incubation double-antigen sandwich enzyme-linked immunosorbent assay kit. Participants' demographic characteristics and degree of exposure to the risk factors associated with HTLV-1 infection were captured using a questionnaire. Statistical analysis of results was done using SPSS version 17. RESULTS: The average age of the pregnant women was 28.94 years (standard deviation 4.17). The age-group with the highest representation was those between the ages of 26 and 30 years. Thirty-six percent of the population was above 30 years old. The result of the tests showed that only one respondent, a 31-year-old pregnant woman tested positive for HTLV-1 antibodies. Therefore, the seroprevalence of HTLV-1 antibodies among pregnant women attending the antenatal clinic at University of Nigeria Teaching Hospital was 0.5%, with a 95% confidence interval of 0%-2.8%. Some of the sociodemographic risk factors of HTLV-1 infection found to be applicable to the 31-year-old woman who tested positive included positive history of previous sexually transmitted diseases, high parity, low socioeconomic status, female sex, and age above 30 years. The pregnant women that participated in this study were exposed to risk factors and behaviors associated with HTLV-1 infection. Some of the pregnant women (17.5%) had contracted sexually transmitted diseases, and 80.5% did not use condoms during coitus. CONCLUSION: The seroprevalence obtained in this study was low, though it is 100% for anyone infected. More prospective and multicenter studies are required to determine the infectivity of HTLV-1 among pregnant women in Nigeria.

Priapism in homozygous sickle cell patients: important clinical and laboratory associations.

OBJECTIVE: To evaluate the relationship between the occurrence of priapism and important steady-state clinical and laboratory parameters in homozygous sickle cell disease (SCD). SUBJECTS AND METHODS: Steady-state clinical and laboratory data were obtained from the medical records of 126 male patients seen in the clinic over a 7-year period. Estimated prevalence rates, correlation coefficients and independent t tests were calculated to assess the relationship between priapism and several important clinical and laboratory indices. Patient data on age, haemoglobin concentrations, the frequency of crises per annum, leucocyte counts, platelet counts, serum bilirubin and aspartate transaminase were evaluated. RESULTS: The prevalence of priapism was determined to be 21.4%, and 22.2% of those affected had erectile dysfunction. There was a significant positive correlation between priapism and older age (p = 0.049) and lower leucocyte counts (p = 0.008). There was no significant relationship with other clinical or laboratory indices. CONCLUSION: About 1 in 4 of all homozygous older SCD patients had priapism, and an approximately similar ratio developed erectile dysfunction; they also had lower steady-state leucocyte counts. Other clinical and laboratory indicators of disease severity in SCD did not positively correlate with the occurrence of priapism, and this may imply an alternative pathogenetic mechanism.

Addition of multimodal therapy to standard management of steady state sickle cell disease.

Most people on folic acid to boost erythropoiesis and prophylactic antimicrobials, the standard management of steady state sickle cell disease (SCD), have unacceptable numbers of crises. The objective of this study was to evaluate the effects of adding multimodal therapy with potassium thiocyanate and omega-3 fatty acids to the standard management of steady state SCD. Pre- and post-treatment numbers of crises and other disease indices were compared in 16 HbSS individuals on folic acid and paludrine after 12 months of adding eicosapentaenoic acid 15 mg/kg/day, docosahexaenoic acid 10 mg/kg/day, and potassium thiocyanate 1-2 mL/day, each milliliter of which contained 250 mg of thiocyanate and 100 micrograms of iodine to prevent hypothyroidism: a possible side-effect due to competitive inhibition of the transport of iodide into the thyroid gland by thiocyanate. Median number of crises reduced from 3/yr to 1/yr (P < 0.0001). There was no evidence of impaired thyroid function. Plasma level of tri-iodothyronine improved (P < 0.0001). Steady state full blood count and bilirubin level did not change significantly. The findings suggest that addition of potassium thiocyanate and eicosapentaenoic and docosahexaenoic acids to standard management of steady state SCD reduces the number of crises. This observation needs to be evaluated in larger studies.

Pilot study of omega-3 fatty acid supplements in sickle cell disease.

In a previous retrospective study, it was observed that the greater the amounts of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the blood, the lesser the number of complications of sickle cell disease (SCD) and the higher the steady state haemoglobin level. SCD causes ischaemia-reperfusion injury and inflammation; which can be ameliorated by a metabolite of DHA that down-regulates expression of pro-inflammatory genes. The objectives of this prospective pilot study were to evaluate the effects of DHA and EPA supplements in SCD, and test the hypothesis that these effects are mediated partly by reducing inflammation. Oral DHA and EPA supplements were given to 16 SCD patients for 6 months. We then compared pre- and post-supplementation values of number of crisis, steady state Hb, plasma unconjugated bilirubin and three indices of inflammation: plasma interleukin-6, blood neutrophil and platelet counts. There was a significant reduction in the plasma level of unconjugated bilirubin, and the number of sickle cell crisis; but not in the markers of inflammation. The pilot data suggest that DHA and EPA supplements reduce the number of crisis and steady state haemolysis in SCD; but provide no evidence that these effects are mediated by reducing inflammation.