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.

Effect of Sickle Cell Trait on Human Immunodeficiency Virus Type 1 Infection.

Introduction: Whereas several studies show that homozygous (HbSS) sickle cell disease protects against human immunodeficiency virus infection, it is not clear if human immunodeficiency virus infection is affected by the heterozygous state of the sickle globin gene (HbAS or sickle cell trait). Objective: To evaluate the effects of sickle cell trait on the prevalence and severity of human immunodeficiency virus type 1 infection in a large patient population. Methods: Hemoglobin genotype was determined by high performance liquid chromatography (HPLC) in 1,226 HIV-1 patients in Nigeria. Their demographic data were documented. Blood CD4+ cell counts and HIV-1 viral load previously determined on the same blood samples to guide clinical care were used as indices of severity of HIV-1 infection. Statistical analysis of the data was done to evaluate the effects of sickle cell trait on the severity and prevalence of HIV-1 infection, relative to the prevalence of 1.4% in the general population of Nigeria. Results and Discussion: The distribution of hemoglobin genotypes among the HIV-1 patients was comparable to that in the general population of Nigeria (Chi-squared statistic =1.025; p value = 0.31, not significant). Neither viral load (p = 0.32) nor blood CD4+ cell count (p = 0.30) was significantly different between all HbAS versus all HbAA patients. There was a trend towards lower viral load in females and a significant interaction between gender and HbAS for viral load (P = 0.018), suggesting that sickle cell trait might be associated with the severity of HIV-1 infection in females. Conclusion: The findings suggest that sickle cell trait might be associated with severity of HIV-1 infection in female, but not all, patients. Larger, prospective studies are required to further investigate the effect of sickle cell trait on HIV-1 infection.

Sickle Cell Disease Clinical Trials and Phenotypes.

Sickle cell disease, one of the world's most common genetic disorders is prevalent in sub-Saharan Africa. The trans-Atlantic slave trade accounted for the gene movement from Africa to the Caribbean and United States of America and lately, migration has resulted in the introduction of the gene to the United Kingdom and other parts of Europe. Different haplotypes exist, however the differences in these haplotypes are not sufficient to explain the different clinical variations within the same region or different settings.

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts.

Alpha-thalassemia and the BCL11A rs1427407 T allele are commonly observed in sickle cell anemia (SCA) patients and are associated with reduced hemolysis and higher hemoglobin F levels, respectively. We investigated whether a high-risk genetic profile, defined as SCA patients who did not inherit either α-thalassemia or the BCL11A rs1427407 T allele, had stronger associations with clinical and laboratory variables than the individual genetic components in the University of Ibadan cohort (n=249). We then replicated our findings in SCA cohorts from the University of Illinois at Chicago (UIC)(n=260) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST)(n=387). High-risk was associated with higher reticulocytes (15.0% vs. 7.8%, P=0.08) and stroke history (6% vs. 1%, P=0.02) than standard risk patients and these associations were more significant than the individual genetic components in the University of Ibadan cohort. These findings were replicated in high-risk patients from UIC and Walk-PHaSST for reticulocytes (UIC: 13.5% vs. 11.8%, P=0.03; Walk-PHaSST: 9.6% vs. 8.2%, P=0.0003) and stroke history (UIC: 32% vs. 22%, P=0.07; Walk-PHaSST: 14% vs. 7%, P=0.01). On combined analysis, high-risk had strong associations with increased markers of hemolysis (hemoglobin ß= -0.29, 95%CI: -0.50 to -0.09; P=0.006; reticulocyte% ß=2.29, 95%CI: 1.31 to 3.25; P=1x10-5) and stroke history (OR=2.0, 95%CI: 1.3 to 3.0; P=0.0002), but no association with frequent vaso-occlusive crises (≥3/year). A high-risk genetic profile is associated with increased hemolysis and stroke history in three independent cohorts. This profile may help identify patients to prioritize for hydroxyurea and for closer monitoring strategies for stroke.