ALBERT

Description: Using clinical, morphological, genetic, and biochemical criteria, we studied ten white and North African families with hereditary elliptocytosis (HE). In four families, elliptocytic individuals displayed a highly significant reduction of band 4.1, which was recorded using two electrophoretic procedures. The 4.1a/4.1b ratio was also significantly reduced, as is usually observed in suspensions enriched in young red cells. This form of HE was invariably associated with the following characteristics: absence of clinical signs; numerous, smooth and well-elongated elliptocytes; dominant transmission; and, when investigated, normal osmotic fragility. Its frequency, among all forms of HE, is about one third as a first estimate, at least in whites and North Africans. In the other six families studied, elliptocytic subjects presented normal 4.1 bands. Again, the 4.1a/4.1b ratio was decreased, reflecting the red cell age- dependent changes in these two components. In three of these families, elliptocytosis was accompanied by clinical signs of variable intensity, and the mode of inheritance could not be unequivocally determined. Therefore, HE with a partially reduced band 4.1 defines a homogeneous variety of HE that can be isolated from other forms of HE. We suggest that it be termed the 4.1 (-) trait, so as to correspond with a previously proposed terminology.

Description: Introduction : Among genetic diseases in hematology, β Thalassemia ranks second after sickle cell disorders in Algeria. Given the seriousness and cost of the care that arises, a national action plan is needed. As a starting point, a national survey is essential to know the epidemiological situation of this disease. Objective : To determine the soci-demographic, diagnosis and evolution characteristics of major and intermediate thalassemia in Algeria. Materiels and Methods : This is a multicenter, retrospective, analytical study of 775 patients with thalassemia major (TM: 598 cases) and intermediate (TI: 177 cases). This national survey is representative of 21 services (Hematology: 19, Pediatrics: 03). The data was collected from medical records on a survey card distributed to all relevant services. Results : As of January 1, 2017, the prevalence of β Thalassemia estimated from this study is of the order of 3.47 cases per 100 000 inhabitants. The current average age of major thalassemia (MT) is 17.90 years, with extremes of [1-44 years], that of intermediate form (IT) is 23 years old with extremes of [1-61 years], the sex ratio is 1.15. The concept of consanguinity is specified in 499 patients and is present in 49.30% of cases, the geographical origin of patients is variable, 53% are from the center of the country and 43% from the east. The circumstances of the diagnosis are known in 87.25% of subjects, these are clinical symptoms in 93.91% of patients, with an average age at diagnosis of 16.31 months for MT and 5.5 years for IT. The diagnosis is neonatal in only 5.68% of cases. Blood cells transfusion needs are known in 80% of our cohort, 86% receive a systematic and regular diet; 554 patients are on chelation therapy, the main modality being deferoxamine or Deferasirox type monotherapy. 40 MT patients received Hematopoetic Stem Cell Transplantation. The monitoring of iron overload was based mainly on the determination of ferritinemia, only 8.8% of patients received cardiac and hepatic MRI. Various complications associated with iron overload have been reported, the most common being: Hepatic injury (48%), heart disease (36%), diabetes (30%), hypothyroidism (29.17). %), with average ages of onset of 26.67, 18, 19, and 14.50 years, respectively. In addition, viral serology was performed in 536 patients, 64 (11.9%) of whom were carriers of anti-HCV Ab. Conclusion : The quality and life expectancy of thalassemic patients has improved significantly in recent years; complications related to iron overload remain the leading cause of death, the means of evaluation remain insufficient in our country. In addition, the care of our patients must be standardized on the national territory. Disclosures No relevant conflicts of interest to declare.

Description: We report on spectrin Oran (alpha II/21), a new spectrin variant found in an Algerian family. It was characterized by the absence of the spots that classically correspond to the alpha II domain using two- dimensional analysis of spectrin limit digests. On the contrary, the abnormal domain was represented by a new set of spots in the 21-Kd and 16-Kd regions, as demonstrated by Western blots using anti-alpha II domain polyclonal antibodies. Spectrin Oran (alpha II/21) was found in the homozygous state in two children belonging to two separate branches of the family. It yields a severe elliptocytosis. Spectrin self- association was altered. The variant was much more difficult to prove in the heterozygous state, in which it results in no clinical and virtually no morphological symptom. In all four parents involved, however, electrophoretic analysis and Western blots showed the existence of the alpha II 21-Kd and 16-Kd peptides. In one parent, who combines spectrin Oran (alpha II/21) and the alpha II type-2 polymorphism, the two-dimensional spots (52, 39, 34, and 29 Kd) were quantified and appeared reduced by 30%: there was an intermediary decrease of spectrin self-association in this person. In the three other parents, spectrin Oran combined with the alpha II type-1 polymorphism. The alpha II type-1 spots (46, 35, 30, and 25 Kd) appeared in normal range, and spectrin self-association was normal. Along with previous observations, the present data emphasize the large fluctuations of the alpha-variant percentage. Provided spectrin Oran was present in a sufficient proportion, we found an associated alteration of the beta II domain (that faces the alpha II domain in the spectrin dimer): the beta II 65-Kd fragment was reduced and the beta II 52-Kd fragment was reciprocally increased.

Description: Spectrin Oran (alpha II/21) has been reported previously as a variant of the alpha II domain. Its expression level is low (10% of total spectrin) in heterozygotes denoting a major disadvantage of the mutated alpha-chain dimer or tetramer with respect to their normal counterparts. Spectrin Oran is associated with symptomatic elliptocytosis in the homozygous state. A 1-minute digestion time allowed to perceive a fast trypsin cleavage (not existing normally) after Arg 890 (helix 3 of repeating segment alpha 9). The responsible change was the lack of amino acids 822 to 862 (helix 2 of repeating segment alpha 8). Such a situation fits with the phasing of spectrin according to which mutated helix 2 and distorted helix 3 are adjacent to one another. The internal position of the structural change accounts for the slight self-association defect. The ultimate genetic lesion was a G to A substitution (intronic position-1) in the acceptor splice site of intron 17 resulting in skipping of exon 18. The substitution also created an acceptor splice site 1 base downstream, but the latter was used at a low grade.

Description: Introduction: The advent of anti-tyrosine kinase has revolutionized the treatment of chronic myeloid leukemia. Indeed, from 2000, the IMATINIB has become internationally the gold standard of treatment for CML chronic phase, while the allogeneic bone marrow transplant was previously, the 1st intention choice, when an HLA-matched donor is available. The aim of this study is to evaluate the efficiency and the toxicity of a treatment with Imatinib(copy), drug used in Algeria to treat patients with a CML chronic phase. The main objective is to evaluate the overall survival and the progression-free survival to these patients. Materials and methods: This is a longitudinal study, National, multicenter, retrospective, which included Algerian patients with chronic phase CML and treated with Imatinib between January 2007 and December 2013. A technical form was established and distributed to different hematology services nationwide, to collect and analysis the following data: Patient's general characteristics, disease circumstances of discovery, clinical and para-clinical examinations at diagnosis (blood count, blood smear, bone marrow aspiration, karyotype, molecular biology, Sokal prognostic classification score and Eutos score). The treatment: Imatinib 400 mg / d, a therapeutic assessment is made according to the ELN recommendations adapted to our conditions and capabilities in Algeria: The complete hematologic response (CHR) at 03 months and molecular response and / or cytogenetic and / or Fish at 03, 06.12, 18.24 months and more according to capabilities. At 03mois and / or 6 months we search a bcr / abl rate

Description: BACKGROUND: In Algeria, the incidence of hematologic malignancies has been difficult to estimate for many years and MDS incidence is unclear because of historical lack of population-based registration and possibly because of under diagnosis. Today, many hematological centers, including 17 university hospitals, have been developed in the entire north and have useful epidemiological data pertinent to MDS. We studied the incidence of MDS and its subtypes, age distribution, geographic distribution and trends in the rate of diagnosis over the last 5 years in Algeria. DESIGN AND SETTING: Retrospective analysis of nationwide survey of all adult cases of MDS (〉16 years) diagnosed between January 2010 and 31 December 2014. PATIENTS AND METHODS: Patients diagnosed with MDS and referred to all departments of hematology at the 17 participating centers between 2010-2014 were identified. Complete demographic and clinical data, laboratory results, treatment modalities were collected and analyzed. RESULTS: Between 2010 and 2014, a total of 243 patients with newly diagnosed MDS have been identified. The sex ratio (M/F) is: 1:08, and the median age is 64.3 years (16 - 82 years). Globally, 27% of MDS are diagnosed in the whole Western region of the country, 56% in the Centre, 14% in the East and 3% in the south. The crude mean annual incidence rate of MDS was 0.07 per 100,000 inhabitants aged ≥15 years old. 11.2% patients were less than 45 years and 42% were older than 70 years.4.3% patients were from rural areas and 6, 2 % were cigarette smokers. Mean hemoglobin level was 7.8 g/dl, mean WBC level was 6134/µl, mean platelets level was 134907/µl, mean VGM level was 92.7 fl and mean ferretin level was 739.31 ng/ml. The mean blood transfusion units were 13.5 units. 36.3% patients had RCMD, 15.9% had RAEB2 and 13.2% had RAEB1. 34.4% patients had cytogenetic abnormalities, and del-5q was more commonly encountered in 22.7%. The IPSS-R was very low in 18.3%, low in 18.3%, intermediate in 11.8%, high in 7.5% and non-specified in 36.6%. Treatment regimens were supportive care (transfusion RBC with chelation, and platelets) and growth factors (EPO, Romiplostine, and G-CSF). At the date of end point, 44% of patients were alive, 26% were death and 31% were lost of follow up. CONCLUSION: Epidemiologic features of our patients are different from the occidental ones. Mean age of presentation of MDS in Algeria is lower than developed countries. The relatively younger age of patients compared to the Western countries may be due to the demographic composition of our population. The annual incidence is still low, but a continuously increasing incidence rate of MDS has been observed throughout the study period and an overall increase in the number of MDS patients diagnosed nationwide over the last five years indicates a need for additional health care resources including curative and therapy-intense strategies, such as stem cell transplant facilities to optimize outcome. Refractory anemia was the most common subtype in both FAB and WHO classification systems and in both genders. The best supportive care was used in all patients in first line treatment and the Iron overload is a permanent feature of MDS. Disclosures No relevant conflicts of interest to declare.