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.

Efficacy and Tolerance of Vascular Electrical Stimulation Therapy in the Management of Vaso-Occlusive Crises in Patients with Sickle Cell Disease: A Phase II Single-Centre Randomized Study in Ivory Coast.

BACKGROUND: Vaso-occlusive crisis (VOC) is the primary cause of hospitalization in patients with sickle cell disease. Treatment mainly consists of intravenous morphine or nonsteroidal anti-inflammatory drugs (NSAIDs), which have many dose-related side effects. The question arises as to whether vascular electrical stimulation therapy (VEST) could be effective or not on VOCs. OBJECTIVE: To measure the effectiveness and safety of VEST in reducing the median time spent in severe VOC. METHODS: We conducted a phase II, single blinded, randomized, controlled, triple-arm, comparative trial. We included thirty (30) adult patients with severe vaso-occlusive crisis. The study arms were divided as follows: our control group (group 0) constituted of 10 patients followed with conventional therapy (Analgesics + Hydration + NSAIDs), while 20 patients were divided equally into two interventional arms-10 patients followed with VEST + Analgesics + Hydration (group 1) and the other 10 patients followed with VEST + Analgesics + Hydration + NSAIDs (group 2). The primary efficacy endpoint was median time to severe crisis elimination. The secondary end points were median time to end-of-crisis, median tramadol consumption, progress of the haemoglobin level over 3 days, side effects, and treatment failure. RESULTS: The age ranged from 14 to 37 years, including 23 women. We noted a beneficial influence of the VEST on the median time to severe crisis (VAS greater than 2) elimination; 17 hours (group 1) against 3.5 hours (group 2) p=0.0166 and 4 hours (group 3) with p value = 0.0448. Similar significant results were obtained on the diminution of total duration of the crisis (VAS over 0) and median tramadol consumption in patients in the interventional arms. CONCLUSION: These statistically significant results in the interventional arms suggest that VEST could be an alternative treatment of VOC in sickle cell patients.

[Homozygous sickle cell disease in Ivory Coast adults]. / Drépanocytose homozygote chez l'adulte ivoirien de plus de 21 ans.

Sickle cell disease is a genetic disease characterized by the synthesis of an abnormal haemoglobin called haemoglobin S. It is the most frequent of the hereditary anomalies of haemoglobin and occurs most commonly in individuals of African descent. Various treatments have considerably improved its prognosis, prolonging the survival of patients, especially those with the most severe, homozygous form. The objective of thisstudy is to describe the epidemiologic, clinical, and laboratory characteristics as well as the disease course and available treatments in adults (aged 21 years or older). This retrospective, descriptive, analytic and non-comparative study included 48 adults of both sexes with homozygous sickle cell disease. Their mean age was 26.1 years (range: 21 to 56 years, and sex ratio 1.3. In all, 70.8% had clinical anaemia, 83.3% were subicteric or icteric and 8.3% had hepatomegaly. Spleen size was normal in 41.7% of patients, and atrophic in 37.5%. No case of splenomegaly was noted and 8.3% had been splenectomised. Haemoglobin rates ranged from 4 g/dL to 12.7 g/dL with an average of 9.5 g/dL, haemoglobin S levels from 83 to 93% with an average of 85.3%, and haemoglobin F levels from 3.5 to 17% with an average of 10.6%. The percentage with fewer than three crises (vasooclusive or haemolytic or both) in a year was 68.7%; 27.1% had from three to five crises, and 4.2% more than five. Disease complications included anaemia in 43.7%, infections in 18.8% and ischaemia in 16.7%; 20.8% had no complications. Age at the beginning of treatment was younger than 5 years in 56.25%, from 5 to 10 years in 29.2%, and older than 10 years in 14.6%. Medical follow-up was regular for 68.7% and irregular for 31.2%. Vaccination was up to date in 58.3. Most patients (83.3%) adhered to their maintenance treatment. In all, 41.7% had not had any blood transfusions, 54.2% had had one or two transfusions, and 4.2% three or more. We compared the patients aged 26 years or younger with those older than 26 and studied the influence of age on different disease variables. Age did not affect the frequency of crises (p = 0.368) or of infections (p = 0.116), the rates of haemoglobin (p = 0.221), haemoglobin S (p = 0.44), or haemoglobin F (p = 0.35), or complications (p = 0.56). Nevertheless, we noted that the frequency of crises, infections, and anaemic complications were higher among the younger patients. Early treatment, regular medical follow-up, maintenance treatment and vaccination have all improved the prognosis of homozygous sickle cell disease considerably. These patients have reached adulthood with relatively few chronic complications.

[Retrospective study about 20 cases of ovarian Burkitt lymphoma at Yopougon teaching hospital in Côte d'Ivoire]. / Étude rétrospective rapportant 20 cas de lymphome de Burkitt de localisation ovarienne pris en charge au CHU de Yopougon en Côte d'Ivoire.

CONTEXT: The maxillo-facial attack was the first described in the Burkitt lymphoma in 1958 by Denis Pearsons Burkitt. Abdominopelvic disorders, particularly ovarian localization are observed more and more by the developments of imagery technics. Our study aimed to describe the epidemiologic, clinical, therapeutic and evolutive aspects of ovarian localization in the endemic Burkitt lymphoma. METHODOLOGY: Twenty files of ovarian Burkitt lymphoma diagnosed in the clinical service of hematology TH of Yopougon during the period August 1995-March 2015 (19 years) were retrospectively analyzed. The epidemiologic, clinical, therapeutic and evolutive parameters were studied. RESULTS: Ovarian Burkitt lymphoma accounted for 20.41% of the population with Burkitt lymphoma and 38.46% for patients with Burkitt lymphoma. The average age was 20.4 years with extremes of 6 and 38 years. The main reasons for consultation were general impairment (85%) and pelvic mass (80%). 75% were in group B clinical scalability. The ovarian mass was bilateral in 60% of cases, heterogeneous in 75% of cases. There was a clear predominance of stage III of Murphy (55%). On the evolutionary level all the patients treated by chemotherapy were in incomplete remission (100%). 10% were alive. 83.33% of the deceased patients had received less than 6 courses of chemotherapy. CONCLUSION: The diagnosis of ovarian endemic Burkitt lymphoma is most often delayed diagnosis and poor prognosis. Improving its management requires early diagnosis.

[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.

Imatinib Mesylate Effectiveness in Chronic Myeloid Leukemia with Additional Cytogenetic Abnormalities at Diagnosis among Black Africans.

Imatinib mesylate provides good results in the treatment of CML in general. But what about the results of this treatment in CML associated with additional cytogenetic abnormalities at diagnosis among black Africans? For this, we retrospectively studied 27 cases of CML associated with additional cytogenetic abnormalities, diagnosed in the department of clinical hematology of the University Hospital of Yopougon in Côte d'Ivoire, from May 2005 to October 2011. The age of patients ranged from 13 to 68 years, with a mean age of 38 years and a sex ratio of 2. Patients were severely symptomatic with a high Sokal score of 67%. CML in chronic phase accounted for 67%. The prevalence of additional cytogenetic abnormalities was 29.7%. There were variants of the Philadelphia chromosome (18.5%), trisomy 8 (14.8%), complex cytogenetic abnormalities (18.5%), second Philadelphia chromosome (14.8%), and minor cytogenetic abnormalities (44.4%). Complete hematologic remission was achieved in 59%, with 52% of major cytogenetic remission. The outcome was fatal in 37% of patients. Death was related in 40% to hematologic toxicity and in 30% to acutisation. The median survival was 40 months.

Characteristics and Results of the Treatment of Multiple Myeloma in the Subject under the Age of 65 at the University Hospital of Yopougon in Abidjan, Côte d'Ivoire.

We retrospectively studied 30 cases of multiple myeloma in patients under the age of 65, diagnosed from 1991 to 2005 in the clinical hematology department of the University Hospital of Yopougon that is a hospital incidence of 2.9 cases/year. The age of patients ranged from 34 to 64 years, with a mean age of 49 years and a sex ratio of 1.73. The professional activity was variable with 3% of radiographers and 10% of farmers. Clinically, the dominant sign was bone pain in 83% of cases. Myeloma was secretory in 93% of cases. It was Ig G-type in 86%, kappa-type in 66% of cases. 86% of patients were anemic, 20% had creatinine >20 mg/L, and 10% had serum calcium >120 mg/L. Geodes were found in 80% of cases. 53% were at stage III of DURIE and SALMON. Complications were infectious (33%), renal (20%), and hemorrhagic (7%). Chemotherapy regimens were VAD (10%), VMCP (30%), and VMCP/VBAP (60%) with 47% of partial responses, 33% of stable disease, and 7% of very good quality partial responses. The outcome developed towards death in 37% and causes of death were renal in 46% of cases. The median survival was only 5.1 months.

Characteristics and Results of the Management of Diffuse Large B-Cell Lymphomas: The Experience of Côte d'Ivoire.

Diffuse large B-cell lymphomas have been little studied in black Africans. The purpose of our study was to determine the characteristics and results of the management of these lymphomas. Patients and Methods. In a descriptive and analytic retrospective study we studied the medical records of 63 patients with diffuse large B-cell lymphoma hospitalized during the period from 1991 to 2007. The diagnosis was made after lymph node or organ biopsy. Response to treatment, OS, PFS, and toxicity were studied. The complete response has been analyzed univariate and multivariate analysis. Results. The median age was 42 years. The sex ratio was 2. The HIV serology was positive in 11 cases, and 8 patients had antiretroviral therapy. In 71% the lymphoma was at stages III and IV of Ann Arbor. IPI was ≥3 in 65%. Complete remission was achieved in 43%. Only 43% of patients had had a good compliance. Progression-free survival at 3 years was 32%, and overall survival at 3 years was 50%. 13% of patients were lost to follow up, and 51% of them died. In terms of analysis the complete remission rate was influenced by the stage of Ann Arbor (P < 0.0001), biological b symptoms (P < 0.01), the IPI (P < 0.0001), and the socioeconomic standing (P = 0.001). In multivariate analysis, only IPI and stage of Ann Arbor influence the complete remission.

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.

[Therapeutic results and evolution of Black African patients with follicular lymphoma: Ivory Coast experience]. / Caractéristiques thérapeutiques et évolutives des lymphomes folliculaires du Noir africain: expérience de la Côte d'Ivoire.

We reported in this study a treatment results about 36 Africans patients with follicular lymphoma. The average age of patients was 18 to 73 years old with a median age at 50.83 years old and a sex ratio of 1. Clinical characteristics of patients are mainly represented by advance stage with 70% of stage III and IV of Ann Arbor classification. Histological, we mainly notified follicular lymphoma constituted of small cells 50%, followed by mixed follicular and large cells lymphomas with respectively 27.78 and 22.22%. Using varieties of therapeutics regiments, we obtained 41.67% of complete remission. There were significant correlations between complete remission and histology subtypes. Indeed, the follicular lymphomas constituted by large cells and mixed cells had higher rate of complete remission with respectively 46.67% and 40% in relation with those of small cells with a higher failure rate. Median follow-up was 24 months, the estimated 5-years overall survival and event-free survival were 22%. After a long period, 25 cases of death have been reported, 5 cases of losing sight and 6 patients are still alive and following treatment. Our results are lowers than the reported case in developing country. This none satisfying was in relation with the lower socio-economical level of the main part of the patients. The short survival delay time of our patients didn't permit time to observe transformation case in diffuse large cell lymphomas.