Determinants of the haemoglobin level in patients with sickle cell disease living in sub-Saharan Africa: Major impact of the country of residence and independent effects of leucocyte and platelet counts and haemolysis.

The degree of anaemia in sickle cell disease (SCD) is a well-known contributor to morbidity and mortality. We aimed to explore the factors affecting haemoglobin (Hb) level in African SCD patients, considering haemolysis biomarkers (LDH and bilirubin level, and reticulocyte count), leucocyte and platelet counts and socio-demographic characteristics (gender, age group, country of residence and BMI). The research was part of the CADRE multinational cohort and involved 3699 SCD patients living in Mali, Senegal, Ivory Coast, Democratic Republic of Congo, Gabon and Cameroon: 2936 SS/Sß0, 587 SC and 176 Sß + patients with median Hb level of 8, 11.3 and 11.2 g/dL respectively (p < 0.001). In multivariate analysis conducted in 1394 SS/Sß0 patients, living in Cameroon, female gender, lower BMI, higher haemolysis markers (especially LDH) and higher leucocyte and platelet counts were independently associated with lower Hb level (all p < 0.05). In 497 SC and 156 Sß + patients, female gender (p < 0.001), lower BMI (p < 0.05) and higher platelet counts (p < 0.001) were independently associated with lower Hb level. Anaemia in African SCD patients is not only associated with haemolysis but also with the country of residence, lower BMI and leucocyte or platelet counts which might reflect inflammation related to infectious burden in the region.

Estimating the risk of child mortality attributable to sickle cell anaemia in sub-Saharan Africa: a retrospective, multicentre, case-control study.

BACKGROUND: Many children with sickle cell disease living in sub-Saharan Africa die before reaching age 5 years. We estimate the child mortality associated with sickle cell anaemia using an indirect approach to overcome the absence of systematic screening at birth. METHODS: We did a retrospective, multicentre, case-control study in five countries in sub-Saharan Africa (Burkina Faso, Democratic Republic of the Congo, Côte d'Ivoire, Mali, and Senegal). Women with at least one child with a confirmed SS haemoglobin phenotype (sickle cell anaemia) and who had at least three (alive or deceased) children from the same father born more than 5 years ago were recruited at an outpatient consultation in a sickle cell disease care centre. Women who had children without sickle cell disease (control group) were recruited from the same area, with inclusion criteria of being a neighbour or relative of one of the mothers included in the study who had a child with sickle cell anaemia, having no child or other first-degree relative with major sickle cell syndrome, having at least three children (alive or deceased) born more than 5 years ago, and having a confirmed haemoglobin AA phenotype. During the mothers' interview, we collected data concerning the mortality of siblings from the same father of a child with sickle cell anaemia and characteristics of the family, such as age at the time of the survey and the level of education of both parents. Mortality rates were calculated for children younger than 1, 5, and 10 years using the Kaplan-Meier method after excluding the index children. We assumed, as per Mendel law, that in families who have a child with sickle cell anaemia and healthy heterozygous parents, 25% of children born on average have sickle cell anaemia. A multivariate Cox model was used to describe socioeconomic and geographical factors associated with mortality. FINDINGS: Between Sept 1, 2017, and Nov 30, 2020, 1563 women who had at least one child with sickle cell anaemia and 4972 women from the same neighbourhood who had children without sickle cell disease were assessed for eligibility. Of 1563 women, 248 were excluded because the genotype of the index child was SC or S ß-thalassaemia. 1315 families with cases of sickle cell anaemia and 1243 control families were included in the study. The median age of children (alive) was 14 years (IQR 8-20) in control families and 13 years (8-19) in families with cases of sickle cell anaemia. 5532 [50·6%] of 10 924 children were male. Mortality rates were 15·3% (95% CI 13·3-17·3) for children with sickle cell anaemia younger than 1 year, 36·4% (33·4-39·4) for those younger than 5 years, and 43·3% (39·3-47·3) for those younger than 10 years. Multivariate Cox survival analysis showed that belonging to a family with sickle cell anaemia (hazard ratio [HR] 2·23, 95% CI 1·96-2·54), living in the Democratic Republic of the Congo (HR 1·64, 1·34-2·01), having an older parent (father or mother age had similar effect; HR 1·12, 1·05-1·19 per 10 years of age), or a significantly higher global Multidimensional Poverty Index (HR 1·09, 1·03-1·14), independently increased the risk of mortality. Whereas, living in Senegal (HR 0·70, 95% CI 0·57-0·86) or having a mother with higher education (high school HR 0·66, 0·55-0·80 or advanced HR 0·41, 0·28-0·61) independently decreased the risk of mortality. INTERPRETATION: Although higher than in high-income countries and affected by non-specific socioeconomic factors, the estimated mortality in children with sickle cell anaemia living in sub-Saharan African cities was substantially lower than previous estimates, suggesting an improvement of sickle cell anaemia care in this setting. FUNDING: Fondation Pierre Fabre. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

[Pre-therapeutic and evolutive characteristics of patients suffering from chronic myeloid leukemia, in Abidjan, Ivory Coast]. / Caractéristiques préthérapeutiques et évolutives des patients atteints de la leucémie myéloïde chronique à Abidjan Côte d'Ivoire.

INTRODUCTION: The diagnosis of chronic myeloid leukemia is based on the presence of translocation t(9,22). Additional cytogenetic abnormalities may exist at diagnosis and have prognostic value. The authors evaluated the relationship between these additional chromosomal abnormalities, clinical presentation, and therapeutic response. METHOD: In a retrospective and comparative study from 2005 to 2015, at Yopougon university hospital, 51 cases of myeloid leukemia were selected, including 22 cases with additional chromosomal abnormalities. RESULTS: Thirteen types of additional Ph1 abnormalities were detected in one group, with a median age of 39years (13-73); a sex ratio of 1.4 and a low social class (49%). The median consultation time is 13months (2-29). Hepatomegaly (54%, P=0.05); fever (81.8%, P=0.0017); bone pain (63.6%, P=0.0001); lymphadenopathies (27.3% P=0.014); poor general condition [WHO>1 (77.3%, P=0.001)], high Sokal index (63.6%, P=0.0019), eosinophilia>5% (72.7, P=0.02) and circulating blastosis were found more frequent in the group with additional abnormalities treated with imatinib mesylate. We obtained 13.6% hematologic remission and 22.7% cytogenetic remission (P=0.02). The average survival was relatively short (20months vs. 76.4months, Log-rank<0.0001). We deplored a high death rate (59.1%). CONCLUSION: The presence of an additional anomaly constitutes a pejorative element refractory to imatinib.

Prevalence and correlates of growth failure in young African patients with sickle cell disease.

Growth failure (GF) in children with sickle cell disease (SCD) tends to decline in high-income countries, but data are lacking in sub-Saharan Africa. We performed a cross-sectional study nested in the CADRE (Cœur, Artères et DREpanocytose) cohort in Mali, Senegal, Cameroon, Gabon and the Ivory Coast. SCD patients and healthy controls aged 5-21 years old were recruited (n = 2583). Frequency of GF, defined as a height, weight or body mass index below the 5th percentile on World health Organization growth charts, was calculated. We assessed associations between GF and SCD phenotypic group, clinical and biological characteristics and history of SCD-related complications. GF was diagnosed in 51% of HbSS, 58% of HbSß0 , 44% of HbSC, 38% of HbSß+ patients and 32% of controls. GF in patients was positively associated with parents' lower education level, male sex, age 12-14 years, lower blood pressure, HbSS or HbSß0 phenotypes, icterus, lower haemoglobin level, higher leucocyte count and microalbuminuria. No association was found between GF and clinical SCD-related complications. In sub-Saharan Africa, GF is still frequent in children with SCD, especially in males and during adolescence. GF is associated with haemolysis and microalbuminuria, but not with the history of SCD-related clinical complications.

Hypercalcémie importante révélant un myélome multiple chez une adolescente de 19 ans

Le myélome multiple est caractérisé par une prolifération des plasmocytes malins sécrétant une immunoglobuline monoclonale complète ou incomplète. C'est une affection de l'adulte mûr. L'âge moyen de survenue est au-delà de 50 ans, rare avant 40 ans et exceptionnel chez les enfants ce qui fait qu'il n'est pas toujours évoqué en première intention chez les sujets jeunes en Afrique Noire. Nous rapportons dans cette étude, l'observation d'une adolescente de 19 ans, sans antécédents pathologiques particuliers, adressée dans notre service pour l'investigation d'une anémie sévère. La symptomatologie était dominée par une hypercalcémie importante inexpliquée associée à une insuffisance rénale. Le myélogramme fait dans le compte d'une anémie normochrome normocytaire arégénérative notait une infiltration médullaire d'environ 12 % par les plasmocytes dysmorphiques. La présence d'une immunoglobuline monoclonale IgG exprimant la chaine légère de type kappa à l'immunofixation des protéines urinaires et les lésions osseuses multiples ont permis de porter le diagnostic de myélome multiple. La chimiothérapie par le protocole VRD a permis une rémission partielle avec correction de la calcémie. L'intérêt de cette étude réside dans le caractère exceptionnel de cette affection à cette tranche d'âge suscitant un intérêt étiopathogénique. Ceci devait motiver les praticiens à y penser devant les signes révélateurs chez les sujets jeunes

Subclinical Cardiac Dysfunction Is Associated With Extracardiac Organ Damages.

Background: Several studies conducted in America or Europe have described major cardiac remodeling and diastolic dysfunction in patients with sickle cell disease (SCD). We aimed at assessing cardiac involvement in SCD in sub-Saharan Africa where SCD is the most prevalent. Methods: In Cameroon, Mali and Senegal, SCD patients and healthy controls of the CADRE study underwent transthoracic echocardiography if aged ≥10 years. The comparison of clinical and echocardiographic features between patients and controls, and the associations between echocardiographic features and the vascular complications of SCD were assessed. Results: 612 SCD patients (483 SS or Sß0, 99 SC, and 19 Sß+) and 149 controls were included. The prevalence of dyspnea and congestive heart failure was low and did not differ significantly between patients and controls. While left ventricular ejection fraction did not differ between controls and patients, left and right cardiac chambers were homogeneously more dilated and hypertrophic in patients compared to controls and systemic vascular resistances were lower (p < 0.001 for all comparisons). Three hundred and forty nine SCD patients had extra-cardiac organ damages (stroke, leg ulcer, priapism, microalbuminuria or osteonecrosis). Increased left ventricular mass index, cardiac dilatation, cardiac output, and decreased systemic vascular resistances were associated with a history of at least one SCD-related organ damage after adjustment for confounders. Conclusions: Cardiac dilatation, cardiac output, left ventricular hypertrophy, and systemic vascular resistance are associated with extracardiac SCD complications in patients from sub-Saharan Africa despite a low prevalence of clinical heart failure. The prognostic value of cardiac subclinical involvement in SCD patients deserves further studies.

Degree of anemia, indirect markers of hemolysis, and vascular complications of sickle cell disease in Africa.

The hyperhemolysis paradigm that describes overlapping "hyperhemolytic-endothelial dysfunction" and "high hemoglobin-hyperviscous" subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2407 SCD patients (1751 SS or sickle ß-zero-thalassemia [Sß0], 495 SC, and 161 sickle ß+-thalassemia [Sß+]), aged 3 years old and over, were included at steady state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity [TRV], microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sß0 adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sß0 adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.

Arterial Stiffness Impairment in Sickle Cell Disease Associated With Chronic Vascular Complications: The Multinational African CADRE Study.

BACKGROUND: Although a blood genetic disease, sickle cell disease (SCD) leads to a chronic vasculopathy with multiple organ involvement. We assessed arterial stiffness in SCD patients and looked for associations between arterial stiffness and SCD-related vascular complications. METHODS: The CADRE (Coeur Artères et Drepanocytose, ie, Heart Arteries and Sickle Cell Disease) study prospectively recruited pediatric and adult SCD patients and healthy controls in Cameroon, Ivory Coast, Gabon, Mali, and Senegal. Patients underwent clinical examination, routine laboratory tests (complete blood count, serum creatinine level), urine albumin/creatinine ratio measure, and a measure of carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AI) at a steady state. The clinical and biological correlates of cf-PWV and AI were investigated by using a multivariable multilevel linear regression analysis with individuals nested in families further nested in countries. RESULTS: Included were 3627 patients with SCD and 943 controls. Mean cf-PWV was lower in SCD patients (7.5±2.0 m/s) than in controls (9.1±2.4 m/s, P<0.0001), and lower in SS-Sß(0) than in SC-Sß(+) phenotypes. AI, corrected for heart rate, increased more rapidly with age in SCD patients and was higher in SCD than in control adults. cf-PWV and AI were independently associated with age, sex, height, heart rate, mean blood pressure, hemoglobin level, country, and hemoglobin phenotype. After adjustment for these correlates, cf-PWV and AI were associated with the glomerular filtration rate and osteonecrosis. AI was also associated with stroke, pulmonary hypertension, and priapism, and cf-PWV was associated with microalbuminuria. CONCLUSIONS: PWV and AI are deeply modified in SCD patients in comparison with healthy controls. These changes are independently associated with a lower blood pressure and a higher heart rate but also with the hemoglobin phenotype. Moreover, PWV and AI are associated with several SCD clinical complications. Their prognostic value will be assessed at follow-up of the patients.

Interest in Determining the CD34+ CD38- Phenotype in the Diagnosis and Prognosis of Acute Leukemia in Abidjan - Côte d'Ivoire.

BACKGROUND: In Côte d'Ivoire, acute leukemias account for 12.5% of hematological malignancies. Acute leukemias are due to an anomaly of the stem cell characterized among other things by the expression of CD34(+) CD38(-) surface markers. This CD34(+) CD38(-) phenotype as well as other factors such as tumor syndrome, high leukocytosis and blasts are considered as important factors of poor prognosis. We therefore proposed to investigate the prognostic value of the expression of CD34(+) CD38(-) markers in acute leukemias in Abidjan. METHODS: We selected 23 patients aged 33 years on whom we performed Complete Blood Count, bone marrow aspiration and immunophenotyping. To search for myeloperoxydase, smears of blood or bone marrow were stained with benzidine and revealed by the use of Hydrogen peroxide. Acute leukemias were then identified and distributed using the score proposed by the European Group for the Immunological characterization of Leukemias. The definitive diagnosis was made by combining morphological characters that serve as the basis for the French-American-British classification as well as cytochemical and immunophenotypic characters. RESULTS: According to the cytological and immunophenotypic classifications, the acute lymphoid leukemia 2 and B IV predominated. 52.2% (12/33) of patients were CD34(+) CD38(-). This phenotype was found in almost all cytological immunophenotypic types. The medullary invasion by blasts (reflection of the tumor mass) of the total sample of CD34(+), CD34(+) CD38(-) patients and those not expressing CD34(+) was respectively 79.4%, 81.25%, 83.3% and 74.8%. CONCLUSION: There was therefore no correlation between medullary blasts and the expression of CD34(+) CD38(-). To the factors we selected it would have been necessary to associate the study of cytogenetic and molecular anomalies to better understand the role of CD34(+) CD38(-) phenotype, concerning prognosis.

[Rare localisations of endemic Burkitt lymphoma: about 21 cases observed in the Haematology Department of the University Hospital of Yopougon Abidjan]. / Localisations exceptionnelles du Lymphome endémique de Burkitt (à propos de 21 cas vus en Côte d'Ivoire).

In this retrospective study, we analysed rare localisations of Burkitt lymphoma observed in the Haematology Department of the University Hospital of Yopougon Abidjan. Over a 10-year study period, we saw 106 patients with Burkitt lymphoma, 21 with unusual localisations. The mean age at onset of symptoms or discovery was 15.48 years, and more patients were female. There were 8 cases of primary Burkitt lymphoma in a rare localisation and 13 cases of unusual localisations of secondary lymphomas. The most frequent of these rare lesions were renal (6), ovarian (4), in peripheral nodes (4), testicular (3), and mammary (3). Still rarer were thyroid, skin, pulmonary, and suprarenal localisations. Clinical manifestations were non-specific and difficult to differentiate from other solid tumours. The CMA protocol produced complete remission in 29% of cases (n=6). Seven patients died. In conclusion, the rare forms of Burkitt lymphoma are non-specific and can be mistaken for other solid tumours. Diagnosis should thus be based on histochemical analysis.

Results of treatment with CMA, a low intermediate regimen, in endemic Burkitt lymphomas in sub-Saharian Africa: experience of Côte d'Ivoire.

African Burkitt lymphomas (BL) are highly aggressive lymphomas mainly affecting children and young adults in Africa. This lymphoma was marked by its high sensitivity to chemotherapy in comparison to Sporadic Burkitt lymphoma. In this study, we evaluated the treatment response and survival of patients with CMA protocol. Eighty-five of the 105 children registered were evaluated for response; there were 46 boys and 39 girls, whose age at diagnosis ranged from 3 to 18 years (median 11 years), admitted to the Hematology National Teaching Hospital of Abidjan in the period 1998-2008 with a diagnosis of BL on histological review and who were given CMA chemotherapy with curative intent are included in this analysis. CMA protocol is a low intermediate regimen of 3 drugs [Cytarabin (ara-C), Methotrexate (MTX), and Cyclophosphamide] with CNS-directed treatment by intrathecal MTX, ara-C and corticosteroid. Fifty-five of 85 patients obtained CR after induction therapy and 10 after 3 supplementary cycle because of partial response. The overall complete remission was 76%. Fifty-three of patients were alive in first CR at a median survival rate period of 2 years (range 82 days to 9 years) and are continuously disease free from Burkitt lymphomas. Twelve patients relapse after CR and died of lymphoma progression. More than 32 patients died, as a result of lymphoma progression. Among the 32 dead, 10 were in Murphy stage IV and all the patients who presented bone marrow involvement died. The projected 5-year overall survival rate was 62%. In conclusion, CMA protocol shows the high sensitivity of African Burkitt lymphoma. This can be considered as a successful result for people living in poor socio-economic conditions with no health insurance.