Clinicopathologic Study of Sickle Cell-associated Kidney Disease: A Nigerian Experience.

BACKGROUND: Improvements in sickle cell disease (SCD) care have resulted in the survival of many patients into adulthood, although this is accompanied by the increased incidence of end-organ damage, including chronic kidney disease (CKD). OBJECTIVES: This study assessed the prevalence, pattern and predictors of renal dysfunction in SCD patients and investigated the associated renal histopathologic changes. METHODS: We evaluated 105 patients with SCD, for proteinuria, estimated glomerular filtration rate (eGFR), and tubular dysfunction. Renal biopsy was conducted on 22 patients who qualified. Data were analysed using SPSS package version 23. RESULTS: Thirty-seven (35.2%) of the 105 patients had CKD, as defined by an eGFR of 60 ml/min/1.73 m2 and/or proteinuria. The fractional excretion of potassium (FEK) was elevated in all patients, whereas the fractional excretion of sodium (FENa) was elevated in 98.1%. Glomerular filtration rate was negatively correlated with irreversible percentage sickle cell count (r = -0.616, P = 0.0001), FEK (r = -0.448, P = 0.0001) and FENa (r = -0.336, P = 0.004). Age, irreversible percentage sickle cell count, haemoglobin levels and FENa were the major predictors of CKD. The histological pattern in the 22 patients who had biopsies was consistent with mesangioproliferative glomerulonephritis 11 (50%), minimal change disease 6 (27.3%), focal segmental glomerulosclerosis 3 (13.6%) and interstitial nephritis 2 (9.1%). CONCLUSIONS: CKD was prevalent in SCD patients, and it was characterised by tubular dysfunction and mesangioproliferative glomerulonephritis. The main predictors of CKD were increased age, severity of vaso-occlusive crisis, worsening anaemia and tubular dysfunction.

Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia with e1a3 BCR-ABL1 transcript in a Nigerian with sickle cell anemia: a case report.

BACKGROUND: The occurrence of acute leukemia in patients with sickle cell anemia is uncommon. The Philadelphia chromosome is the hallmark of chronic myeloid leukemia. However, it may also be associated with acute lymphoblastic leukemia and acute myeloblastic leukemia. The common BCR-ABL1 transcripts seen in acute lymphoblastic leukemia are e1a2, e13a2, and e14a2, while other transcripts such as e1a3, e13a3, and e6a2 occur rarely. This report describes the presentation, management, and outcome of the occurrence of B-cell acute lymphoblastic leukemia with the rare e1a3 BCR-ABL1 transcript in a patient with sickle cell anemia. CASE PRESENTATION: A 19-year-old male Nigerian, a known sickle cell anemia patient was admitted on account of severe vaso-occlusive crisis. Examination revealed fever, palor, and jaundice. Full blood count showed anemia and leukocytosis. Peripheral blood and bone marrow smears revealed numerous large and small lymphoblasts in keeping with the L2 subtype of acute lymphoblastic leukemia based on the French-American-British classification. Further evaluation was in keeping with a diagnosis of BCR-ABL1-positive mature B-cell acute lymphoblastic leukemia associated with the rare e1a3 transcript. He was commenced simultaneously on induction chemotherapy and Imatinib while being prepared for allogeneic stem cell transplantation. However, he died  six  months after diagnosis from meningoencephalitis. CONCLUSION: The occurrence of acute lymphoblastic leukemia with a rare BCR-ABL1 e1a3 transcript in association with sickle cell anemia is uncommon and associated with poor prognosis.

Management of Chronic Lymphocytic Leukemia in Less-Resourced Countries.

ABSTRACT: Despite the practice-changing advances achieved in the prognostic stratification and treatment of chronic lymphocytic leukemia (CLL), a large fraction of the world population resides in countries where access to many of these advances remains unavailable or subject to severe constraints. Although some of these countries display incidence rates of CLL that are lower than those of developed Western countries, a large number of patients are expected to be diagnosed with CLL in these regions every year. In this article, we review issues regarding management of CLL in some less-resourced countries, with a focus on the evidence basis for epidemiological and clinical information on this disease, the availability of diagnostic and therapeutic resources, and participation in clinical trials. Going forward, challenges that still need to be addressed include the development of unified countrywide registries, guidelines for management applicable to each country, wider availability of prognostic tools, access to new drugs, and policies that ensure these drugs are affordable to all patients worldwide.

Ethnic and geographic diversity of chronic lymphocytic leukaemia.

East Asians, Asian Indians and Amerindians have a five to ten-fold lower age-adjusted incidence rate (AAIR) of chronic lymphocytic leukaemia (CLL) compared with persons of predominately European descent. The data we review suggest a genetic rather than environmental basis for this discordance. All these populations arose from a common African Black ancestor but different clades have different admixture with archaic hominins including Neanderthals, Denisovans and Homo erectus, which may explain different CLL incidences. There are also some differences in clinical laboratory and molecular co-variates of CLL between these populations. Because the true age-adjusted incidence rate in African Blacks is unknown it is not possible to determine whether modern Europeans acquired susceptibility to CLL or the other populations lost susceptibility and/or developed resistance to developing CLL. We also found other B-cell lymphomas and T- and NK-cell cancers had different incidences in the populations we studied. These data provide clues to determining the cause(s) of CLL.

Distribution of BCR-ABL1 Transcript Variants in Nigerians with Chronic Myeloid Leukemia.

The distribution of BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") in Nigerians with chronic myeloid leukemia (CML) had not been previously studied. In addition, there is paucity of data on the impact of BCR-ABL1 transcript variants on clinical presentation and survival in CML patients in Nigeria. The BCR-ABL1 transcript variants were analyzed in 230 Imatinib-treated CML patients at diagnosis. Patients with incomplete data (n = 28), e19a2 (n = 3) and e1a2 (n = 1) were excluded from analysis of transcript variant on disease presentation and survival leaving only 198. The frequencies of BCR-ABL1 transcript variants were 30 (13.0%), 114 (49.6%), 82 (35.7%), three (1.3%) and one (0.4%) for e13a2, e14a2, co-expression of e13a2/e14a2, e19a2 and e1a2, respectively. A significantly higher platelet count was found in patients with e13a2 variant (531.1 ± 563.4 × 109/L) than in those expressing e14a2 (488.2 ± 560.3 × 109/L) or e13a2/e14a2 (320.7 ± 215.8 × 109/L); p = 0.03. No significant differences were found between the variants with regards to gender, age, phase of disease at diagnosis, total white blood cell count, neutrophil percentage, hematocrit, splenomegaly or hepatomegaly. Overall survival was higher but not statistically significant (p = 0.4) in patients with e14a2 variant (134 months) than in e13a2 (119 months) and co-expression of e13a2/e14a2 (115 months). Nigerian CML patients have the highest incidence of co-expression of e13a2 and e14a2. Distinct disease characteristics which contrast with findings from the Western countries were also identified in Nigerians which may be due to genetic factors.

Paediatric to adult transition care for patients with sickle cell disease: a global perspective.

Sickle cell disease is a life-threatening inherited condition designated as a public health priority by WHO. Increased longevity of patients with sickle cell disease in high-income, middle-income, and low-income countries present unprecedented challenges for all settings; however, a globally standardised solution for patient transition from paediatric to adult sickle cell disease health care is unlikely to address the challenges. We established a task force of experts from a multicountry (the USA, Europe, Middle East, and Africa) consortium. We combined themes from the literature with viewpoints from members of the task force and invited experts to provide a global overview of transition care practice, highlighting barriers to effective transition care and provide baseline recommendations that can be adapted to local needs. We highlighted priorities to consider for any young person with sickle cell disease transitioning from paediatric to adult health care: skills transfer, increasing self-efficacy, coordination, knowledge transfer, linking to adult services, and evaluating readiness (the SICKLE recommendations). These recommendations aim to ensure appropriate benchmarking of transition programming, but multisite prospective studies are needed to address this growing public health need.

The Inflammatory Response to Surgery in Sickle Cell Disease Patients Undergoing Cholecystectomy.

BACKGROUND AND OBJECTIVES: Patients with sickle cell anemia (SCA) may have elevated inflammatory markers in health, and this may be heightened after open operations. The inflammatory response of patients with SCA after minimally invasive surgeries has not been fully explored. PATIENTS AND METHODS: Consecutive patients with SCA and with hemoglobin AA (HbAA) undergoing laparoscopic cholecystectomy for acute cholecystitis were recruited into the study. Blood samples were taken before induction of anesthesia (0-h); at 4, 12, 24, and 48 h; and on postoperative day 7. Samples were analyzed for serum C-reactive protein and interleukin (IL)-1 through IL-18. RESULTS: Twenty-three patients, including 9 with SCA and 14 with HbAA, were recruited with 4 cases performed by open laparotomy. At 0-h, proinflammatory IL-1 levels (6.1 versus 4.8) and C-reactive protein levels (32.5 versus 26.6) were higher in patients with hemoglobin SS (HbSS) than in patients with HbAA, respectively. Over time, inflammatory markers were generally higher at each time-point for patients with HbSS compared with patients with HbAA for both proinflammatory and anti-inflammatory cytokines, rising immediately after surgery and up to 48 hours, then returning to baseline by postoperative day 7. There was a higher mean IL-1 level across all time-points in the HbSS group than in the HbAA group (P = .04). CONCLUSION: This exploratory study found an enhanced inflammatory response to cholecystectomy in patients with SCA compared with patients with HbAA. Minimally invasive surgical strategies for this patient group may help to mediate this response.

Studies on the effect of a nutritious vegetable, Telfairia occidentalis, on HbSS blood.

Medicinal plants have been used traditionally in Africa, especially Nigeria, in the management of sickle cell disorder (SCD) whose treatment has been mainly palliative. The antisickling properties of ethanol extract of Telfairia occidentalis Hook, F. (TO) (Family Cucurbitaceae) leaf was tested in vitro at concentrations 1, 2, 4, 8 and 16 mg/mL using inhibitory and reversal models. Nitrogen gas was used to induce hypoxia for 1 h. The effect of TO on red cell density and cell membrane were also determined. The methanol sub fraction of TO extract was subjected to GC/MS to identify some of the active compounds. The TO gave antisickling activities of 78.84 ± 1.34% inhibition and 95.4 ± 0.81% reversal, which are significantly (p < 0.05) higher than that of Ciklavit®. The TO extract gave a change in density of 17.83 ± 0.77% and a dose dependent activity on RBC membrane. Methyl 9-cis 11- trans-octadecadienoate; 1, 4- benzenedicarboxylic acid; 9, 12-octadecadienoic acid (Linoleic acid); and hexadecanoic acid methyl ester (palmitic acid); were identified from TO ethanol leaf extract for the first time using GC/MS. This study authenticated the ethnomedicinal claims of the use of T. occidentalis in the management of sickle cell disorder.

Preliminary Evaluation of a Point-of-Care Testing Device (SickleSCAN™) in Screening for Sickle Cell Disease.

Sickle cell disease affects about 150,000 births annually in Nigeria. Early diagnosis is hampered by factors such as centralized and urban localization of laboratories, high cost of diagnostic equipment and inadequate skilled manpower to operate them. The need for a low-cost, portable, easy-to-use diagnostic test for sickle cell disease is critical, especially in resource-poor countries. In this study, we evaluated the performance characteristics of a novel point-of-care testing device (SickleSCAN™), and its acceptability and feasibility, as a possible screening tool for sickle cell disease. In the first phase, we assessed the performance characteristics of SickleSCAN™ by evaluating 57 subjects comprising both children and adults attending a primary health center, for Hb SS (ßS/ßS; HBB: c.20A>T), Hb SC (ßS/ßC; HBB: c.19G>A) and Hb AS (ßA/ßS) using SickleSCAN™, cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC). Performance characteristics such as diagnostic sensitivity and specificity were compared to HPLC as a standard method. We subsequently undertook a second phase wherein the acceptability and feasibility of the device for sickle cell disease screening, was evaluated using semi-structured and structured questionnaires among 197 healthcare personnel and 221 subjects, respectively. Sickle cell disease was carried by 3.4% of the subjects. The diagnostic sensitivity, specificity and test efficiency of SickleSCAN™ for sickle cell disease (Hb SS and Hb SC), were 100.0, 98.2 and 98.2%, respectively. Findings from this study showed SickleSCAN™ to be a viable screening tool that can easily be applied in community-based screening for early diagnosis of sickle cell disease with little expertise and low cost.

Pulmonary hypertension in Nigerian adults with sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is the commonest hemoglobinopathy and is associated with high morbidity and mortality. Pulmonary hypertension (PH) is reported to play a significant role in this regard. There is very limited literature on PH in SCA in Nigeria. OBJECTIVES: The objectives of this study were to determine the prevalence of Doppler-derived PH in SCA, assess its influence on exercise capacity, and determine the correlates and predictors of measures of estimated pulmonary pressure. METHODS: A total of 92 SCA subjects had echocardiography and 6-minute self-paced walking exercise. PH was diagnosed by Doppler echocardiography on finding a tricuspid regurgitant velocity (TRV) of ≥2.5 m/s. The pulmonary flow profile was also assessed to estimate mean pulmonary arterial pressure (MPAP). RESULTS: Doppler-derived PH was detected in 23.9% of adults with SCA. The 6-minute walking distance (6MWD) was significantly lower in SCA adults with PH than in those without PH (380.33 ± 63.17 m vs 474.28 ± 76.74 m; p = 0.014). TRV and estimated MPAP had a significant inverse correlation with the 6MWD (r = -0.442; p < 0.001 and r = -0.571; p < 0.001, respectively). CONCLUSION: PH as derived by Doppler is common in Nigerian adults with SCA and has a significantly negative influence on exercise capacity. Screening for PH should be encouraged to optimize management and thus improve their quality of life and life expectancy.

Chronic Myeloid Leukemia in Nigerian Patients: Anemia is an Independent Predictor of Overall Survival.

OBJECTIVES: The advent of the tyrosine kinase inhibitors has markedly changed the prognostic outlook for patients with Ph(+) and/or BCR-ABL1 (+) chronic myeloid leukemia (CML). This study was designed to assess the overall survival (OS) of Nigerian patients with CML receiving imatinib therapy and to identify the significant predictors of OS. METHODS: All patients with CML receiving imatinib from July 2003 to June 2013 were studied. The clinical and hematological parameters were studied. The Kaplan-Meier technique was used to estimate the OS and median survival. P-value of <0.05 was considered as statistically significant. RESULTS: The median age of all 527 patients (male/female = 320/207) was 37 (range 10-87) years. There were 472, 47, and 7 in chronic phase (CP), accelerated phase, and blastic phase, respectively. As at June 2013, 442 patients are alive. The median survival was 105.7 months (95% confidence interval [CI], 91.5-119.9); while OS at one, two, and five years were 95%, 90%, and 75%, respectively. Multivariate Cox regression analysis revealed that OS was significantly better in patients diagnosed with CP (P = 0.001, odds ratio = 1.576, 95% CI = 1.205-2.061) or not in patients with anemia (P = 0.031, odds ratio = 1.666, 95% CI = 1.047-2.649). Combining these variables yielded three prognostic groups: CP without anemia, CP with anemia, and non-CP, with significantly different median OS of 123.3, 92.0, and 74.7 months, respectively (χ (2) = 22.042, P = 0.000016). CONCLUSION: This study has clearly shown that for Nigerian patients with CML, the clinical phase of the disease at diagnosis and the hematocrit can be used to stratify patients into low, intermediate, and high risk groups.

Blood transfusion services for patients with sickle cell disease in Nigeria.

BACKGROUND: Safe, timely red blood cell transfusion saves lives and chronic transfusion therapy (CTT) prevents or limits morbidities such as stroke, therefore improving quality of life of patients with sickle cell disease (SCD). METHODS: This questionnaire-based study assessed the ability of sickle cell centers in Nigeria to provide safe blood to patients with SCD between March and August 2014. RESULTS: Out of the 73 hospitals contacted, responses were obtained from 31. Twenty four (78%) hospitals were unable to transfuse patients regularly due to blood scarcity. Packed red blood cells were available in 14 (45%), while only one provided leukocyte-depletion. Most centers assessed donor risk and screened for HIV in 30 (97%), hepatitis B in 31(100%) and hepatitis C in 27 (87%) hospitals. Extended phenotyping and alloantibody screening were not available in any center. A quarter of the hospitals could monitor iron overload, but only using serum ferritin. Access to iron chelators was limited and expensive. Seventeen (55%) tertiary hospitals offered CTT by top-up or manual exchange transfusion; previous stroke was the most common indication. CONCLUSION: Current efforts of Nigerian public hospitals to provide safe blood and CTT fall short of best practice. Provision of apheresis machines, improvement of voluntary non-remunerated donor drive, screening for red cell antigens and antibodies, and availability of iron chelators would significantly improve SCD care in Nigeria.

Degrees of kidney disease in nigerian adults with sickle-cell disease.

OBJECTIVE: To study degrees of chronic kidney disease (CKD) using creatinine clearance in adult Nigerian patients with sickle-cell disease (SCD). METHODS: One hundred SCD patients, made up of 79 HbSS (homozygous haemoglobin S) patients and 21 HbSC (heterozygous haemoglobins S and C) patients, were investigated prospectively, along with 50 normal controls. Their sociodemographic data, weight and drug history were documented. Each participant underwent dipstick urinalysis, and creatinine clearance was calculated following a 24-hour urine collection and serum creatinine measurement. They were categorized into stages of CKD based on the creatinine clearance. RESULTS: Of the 79 HbSS patients, 14 (18%), 28 (35%), 33 (42%) and 4 (5%) had stage 1, 2, 3 and 4 CKD, respectively. In the HbSC group, 3 (14%), 9 (43%) and 9 (43%) patients had stage 1, 2 and 3 CKD, respectively. Proteinuria was noted in 16 (20%) HbSS patients but not in any of the HbSC patients. Of the subjects aged ≤24 years (n = 49), 9 (18%), 18 (37%), 21 (43%) and 1 (2%) had stage 1, 2, 3 and 4 CKD, respectively. Of those aged >24 years (n = 51), 8 (16%), 19 (37%), 21 (41%) and 3 (6%) had stage 1, 2, 3 and 4 CKD, respectively. None of the subjects had stage 5 CKD. CONCLUSION: In this study, the adult subjects with SCD had various degrees of CKD. Adequate follow-up and active intervention are advocated to delay the onset of end-stage nephropathy.