Epidemiological and immunochemical parameters of monoclonal plasma cell dyscrasias of 2121 cases in Algeria.

BACKGROUND: Plasma cell dyscrasias (PCD) are a heterogeneous group of diseases characterized by the expansion of monoclonal bone marrow plasma cells that produce a monoclonal immunoglobulin (M-component). PURPOSE: This is a retrospective study that describes the epidemiological, immunochemical features and etiology of monoclonal gammopathies diagnosed between 1998 and 2016 in the Teaching Hospital Beni-Messous of Algiers. PATIENTS AND METHODS: 2121 cases of monoclonal gammopathies (MG) were collected during this period. Serum/urine protein electrophoresis, serum/urine immunofixation and serum free light chain measurements were used to demonstrate M protein. RESULTS: The middle age of the patients at the time of the diagnosis were 62.96 ± 13.19 years with extremes ranging from 07 to 99 years. The study included 1013 (47, 76 %) men and 1108 (52, 23 %) women with a sex ratio 0,91. Isotypes repartition was: IgG (60.91 %), IgA (17.91 %), light chain (10.46 %), IgM (6.6 %), IgD (1.03 %) and IgE (0.09 %) of cases. The most frequent diagnosis was: Multiple Myeloma (55.20 %), followed by monoclonal gammopathy of undetermined significance (34.13 %). CONCLUSION: In our study, two particularities were noted. There is no male predominance in Algerian PCD patients. Moreover, we observed a higher frequency of light chain multiple myeloma and lower frequency of IgM isotype compared to western studies.

IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum ß2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM.

Establishing a harmonized haemophilia registry for countries with developing health care systems.

Over recent decades tremendous progress has been made in diagnosing and treating haemophilia and, in resource-rich countries, life expectancy of people with haemophilia (PWH) is now close to that of a healthy person. However, an estimated 70% of PWH are not diagnosed or are undertreated; the majority of whom live in countries with developing health care systems. In these countries, designated registries for people with haemophilia are often limited and comprehensive information on the natural history of the disease and treatment outcomes is lacking. Taken together, this means that planning efforts for future treatment and care of affected individuals is constrained in countries where it is most needed. Establishment of standardized national registries in these countries would be a step towards obtaining reliable sociodemographic and clinical data for an entire country. A series of consensus meetings with experts from widely differing countries with different health care systems took place to discuss concerns specific to countries with developing health care systems. As a result of these discussions, recommendations are made on parameters to include when establishing and harmonizing national registries. Such recommendations should enable countries with developing health care systems to establish standardized national haemophilia registries. Although not a primary objective, the recommendations should also help standardized data collation on an international level, enabling treatment and health care trends to be monitored across groups of countries and providing data for advocacy purposes. Greater standardization of data collation should have implications for optimizing resources for haemophilia care both nationally and internationally.

A population-based study of the epidemiology and clinical features of adults with acute myeloid leukemia in Algeria: report on behalf of the Algerian Acute Leukemia Study Group.

BACKGROUND AND OBJECTIVES: In Algeria, the incidence of hematologic malignancies has been difficult to estimate for many years. Today, many hematological centers, including 14 university hospitals, have been developed in the entire north and have useful epidemiological data pertinent to acute myeloid leukemia (AML). We studied the incidence of AML and its subtypes, age distribution, geographic distribution and trends in the rate of diagnosis over the last 5 years in Algeria. Secondary goals were to study trends of referral of AML cases from various regions to specific centers to assess the needs for health infrastructure and change of current practices. DESIGN AND SETTING: Retrospective analysis of nationwide survey of all adult cases of AML (>16 years) diagnosed between 1 January 2006 and 31 December 2010. PATIENTS AND METHODS: A survey form was distributed to all departments of hematology at the 15 participating centers. RESULTS: The 1426 cases of AML diagnosed during the study period represented an annual incidence of 0.91/100000 persons with a male to female (M/F) ratio of 1:16 and a median age of 45 years (range, 16-82 years). Nationally, 20% of cases AML were diagnosed in the whole western region of the country, 47% in the central and 33% in the east. There was a trend of continuous increase in the rate with age and in the rate of diagnosis over the last 5 years. The most common subtype was M2, followed by M4 and M5. CONCLUSION: An overall increase in the number of AML 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. The relatively younger age of patients compared to the Western countries may be due to the demographic composition of our population.

[Hodgkin disease, clinical stages IA-IIB: evaluation of the value of cisplatin. Preliminary results]. / Maladie de Hodgkin, stades cliniques IA-IIB: évaluation de l'intérêt du cisplatine. Résultats préliminaires.

Cisplatinum is highly effective in numerous solid tumors and was evaluated in Hodgkin's disease clinical stages (CS) I/II. Sixty-five patients (43 male, 22 female; median age 25, with 12 patients under 16: CS IA-IIA 41, IB 5, IIB 19) were randomly assigned to one of the following arms (PAF87 protocol): 3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine with methylprednisolone) cycles (ABVD arm) or 3 ABVD plus cisplatinum cycles (ABVD-Plt arm) followed by radiotherapy (RT); extended field (40 Gy) RT with a short paraaortic field including the spleen (30 Gy) was then administered in the ABVD arm; extended field (30 Gy) without lombosplenic port prophylaxis. RT was administered in ABVD-Plt arm when patients were in complete remission (CR) after chemotherapy (CT). Median follow-up was 35 months (6-62 months). During CT, 1 patient (ABVD-Plt) died from viral meningo-encephalitis; five patients (1 ABVD, 4 ABVD-Plt) stopped treatment because of emesis, of whom three receiving only 1.5-2.5 (ABVD-Plt) cycles, are still in CR after 13-60 months. Fifty-five patients (27 ABVD-Plt) were in CR after CT. Among the 27 ABVD-Plt patients, all in CR after RT, two died (one from myocardial infarction and one from immunoblastic lymphoma); one patient from the ABVD arm died from gastro-intestinal hemorrhage in 1st CR. No ABVD-Plt patient relapsed; 1 ABVD patient relapsed in non-irradiated area. At five years, actuarial survival/relapse-free survival was 96.1/90% and 88.2/100% for ABVD and ABVD-Plt patients, respectively.

High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease.

PURPOSE: For patients with Hodgkin's disease (HD) who do not achieve complete response (CR), who experience a relapse within the first year of CR, and for those who have two or more relapses, the outcome is poor. Salvage chemotherapy regimens at conventional doses produce a CR rate that ranges from 10% to 50% and a 5-year disease-free survival (DFS) between 10% and 25%. On the other hand, high-dose chemotherapy regimens given in combination with bone marrow transplantation (BMT) produce a CR rate that ranges from 40% to 80% and a 3-year DFS of approximately 40%. We report the 5-year results of a prospective study in patients with refractory HD who were treated with three courses of intensive chemotherapy without BMT. PATIENTS AND METHODS: Thirty-nine adult patients with refractory HD were treated with three courses of intensive chemotherapy. Each cycle of chemotherapy comprised vindesine 1 mg/m2/d in continuous intravenous (IV) infusion from day 1 to day 5; Adriamycin (doxorubicin; Roger Bellon Laboratories, Neuilly, France) 40 mg/m2/d in continuous IV infusion from day 1 to day 3; carmustine 140 mg/m2/d at day 3; etoposide 200 mg/m2/d from day 3 to day 5; and methylprednisolone 120 mg/m2/d from day 1 to day 5. After the third cycle of chemotherapy, irradiation (20 Gy) was performed whenever possible and depended on previous irradiation. RESULTS: At the end of the treatment, 31 patients (79%) were in CR. Among these patients, 10 relapsed after a median time of 3 months. The overall 5-year survival rate was 46%. The freedom from progression (FFP) and the freedom from treatment failure (FFTF) rates were 48% and 43%, respectively. The main toxicities were hematologic (neutropenia and thrombocytopenia) and digestive. Four patients died due to treatment-related complications (two from septic shocks, one from respiratory insufficiency, and one from posttransfusional AIDS). CONCLUSION: The results of this study seem to be comparable to those results obtained with high-dose chemotherapies with autologous BMT.

Partial splenectomy in homozygous beta thalassaemia.

Partial splenectomy was performed on 30 patients with homozygous beta thalassaemia to reduce blood requirements and to avoid the risk of overwhelming postsplenectomy infections; 24 patients had thalassaemia major and six thalassaemia intermedia. Five patients received a high transfusion regimen before and after surgery and 25 a lower one. Follow up after surgery ranged from one to four years. Partial splenectomy improved the long term haematological state in the six patients with thalassaemia intermedia. Recurrence of hypersplenism occurred in nine of the 24 patients with thalassaemia major, however, and complete splenectomy was required. Serum IgM concentrations were not significantly modified by surgery. The mean (SD) residual spleen after surgery was 4.45 (2.36) cm measured by scintigraphy. No severe infections occurred after surgery; however, most patients were routinely treated with phenoxymethylpenicillin and the protective effect of the remaining spleen could not be exactly determined. Because of the possibility of recurrence of hypersplenism, routine partial splenectomy when splenectomy is needed in thalassaemia major is not advised, except in children under 5 years whose risk of overwhelming postsplenectomy infection is greatest.

Alpha globin gene triplication in severe heterozygous beta thalassemia.

In an Algerian family, three sibs with an unusually severe heterozygous beta-thalassemia and two sibs with a typical heterozygous beta-thalassemia were found. Both conditions were transmitted vertically. Globin chain synthesis and DNA restriction enzyme analysis showed that the unusual severity of heterozygous beta-thalassemia observed in this family is related to an overproduction of alpha-globin chains originating from an alpha-globin gene triplication.

Sickle cell beta-thalassaemia compared with sickle cell anaemia in Algeria.

Clinical, haematological and biochemical features in 42 subjects with S-beta thalassaemia (31 subjects with S-beta thalassaemia and 11 subjects with S-beta+ thalassaemia); and in 42 with homozygous sickle cell disease were compared. Persistent splenomegaly was more common and painful crises less common in the S-beta thalassaemia group. Total Hb was higher and reticulocyte count lower in S-beta+ thalassaemia than in S-beta thalassaemia or SS disease. Microcytosis was marked in the S-beta thalassaemia group while the MCV was normal in sickle cell anaemia. Hb F was significantly higher in the S-beta thalassaemia group, without any influence on the severity of the disease. Many features suggest that sickle cell thalassaemia is more severe in Algeria than in Negro subjects and similar to the disease in Italian patients.

Indirect evaluation of a gene frequency: calculation of beta-thalassemia frequency in Algeria based on associated hemoglobin variants frequency.

The gene frequency (q) of beta-thalassemia (T) is more difficult to evaluate directly than the frequency of hemoglobin variants (V), Hb S and Hb C being the most frequent ones in Algeria. Among 150 subjects with a phenotype V, we identified 76 compound heterozygotes VT(0) (T(0) = beta(0)-thalassemia) and 74 homozygotes VV: qT(0) is therefore practically equal to qV. Calculation based on the investigation of 54 subjects detected during the same period (33 VT among which 23 VT(0) and 21 TT among which 9 T(0) T(0) yields qT = 1.43 qT(0) = 1.43 qV. According to Cabannes [1965], qV is equal to 0.0113, qT is 1.43 X 0.0113 = 0.0162. This indirect method, based on investigation of patients, gives a less precise evaluation of gene frequency than a direct method based on large population screening. This evaluation, however, is sufficient to estimate the incidence of beta-thalassemia and its impact from a public health point of view.

Hemoglobin H disease from Algeria: genetic and molecular characterization.

A case of Hb H disease from Algeria was studied at the genetic and molecular level in order to delineate the pattern of alpha-thalassemia in the Mediterranean population. The family study indicated that both parents had the hematological and clinical manifestation of alpha-thalassemia trait and that the affected sibling had homozygous alpha-thalassemia with 5.6% Hb H, microcytosis and an alpha-/non-alpha-biosynthetic ratio of 0.64. Hybridization in globin cDNA alpha excess suggested that the molecular defect responsible for this form of alpha-thalassemia is a partial deletion of the haploid stock of alpha-globin genes. The Algerian case of Hb H disease studied thus differs from Asian and Negro cases by the mode of inheritance of the alpha-thalassemia mutation involved.

Heterogeneity in beta 0 thalassemia from Algeria: genetic, clinical and molecular studies.

Six Algerian patients with beta 0 thalassemia are presented, in addition to the two patients already reported (Godet et al., 1977). Family studies indicate that all the patients had homozygous beta thalassemia characterized by absence of beta globin chain synthesis in peripheral blood. The clinical severity varies from one family to the other and within the same family, from typical Cooley's anemia to thalassemia intermedia and appears to be related to the child death rate observed in each family. The gamma/alpha biosynthetic ratio was 0.36-0.40 in seven patients and 0.2 in the most seriously affected patient. The mRNA beta content in peripheral reticulocytes was less than 1.5% of mRNA alpha in seven patients and 13.3% in one patient. These results indicate that Algerians homozygous for beta 0 thalassemia are heterozygous at the clinical, biochemical and molecular levels.

Phenotypic variation in red cell G-6PD deficiency in heterozygotes.

Erythrocyte G-6PD activity in 69 heterozygotes has a log-normal distribution, a fact which cannot be solely attributed to random X chromosome inactivation. Others factors - genetic and individual - are suggested by intrafamilial clusting and post-natal variability of phenotype.

beta-O-thalassemia from Algeria: genetic and molecular characterization.

beta-Thalassemia is a major public health problem in Algeria. During a survey, a family including two cases of betaO-thalassemia was studied. The family study indicated that two of the affected siblings had homozygous beta-thalassemia; there were also both normal and heterozygous siblings, and both parents had beta-thalassemia trait. In the two cases of betaO-thalassemia there was no hemoglobin A in the peripheral blood, and no beta-globin chain synthesis in whole cell incubations. Hybridization of purified complementary DNA specific for alpha- and beta-globin messenger RNAs demonstrated less than 1% mRNAbeta relative to mRNAalpha in circulating reticulocytes, and for one case in total RNA from bone marrow. There is no apparent beta-globin gene deletion as determined by hybridization in globin cDNAbeta sequence excess. Therefore the Algerian cases studied are similar in molecular pathology to some Southern Italian and Asian cases described previously, and differ from other Italian and Chinese betaO-thalassemias, in which hybridizable mRNAbeta has been demonstrated, and from deltabetaO-thalassemia, which is caused by a gene deletion.

[1st cases of alpha-thalassemia in Algeria: 12 cases of hemoglobinosis H]. / Premières observations d'alpha-thalassémie en Algérie: 12 cas d'hémoglobinose H.

These first cases of hemoglobinosis H show that alpha-thalassemia is not a simple curiosity in this part of the Western Mediterranean. They are not localised to a single part of Algeria as the areas from which the patients came were more than 150 km apart. They suggest that the enquiry should be continued by other means to determine the prevalence and pathological incidence.

[Clinical and biological aspects of beta-thalassemia. Apropos of 176 cases]. / Aspects cliniques et biologiques des bêta-thalassémies. A propos de 176 observations.

The study of 176 subjects with beta-thalassemia, associated or not with a hemoglobinopathy, shows great diversity. The hemoglobin C thalassemias are less severe and form a fairly homogeneous group. Sickle cell thalassemia cases have more marked anemia and the disease takes on more varied forms, no doubt because the main mechanism of the anemia, the hyperhemolysis, is influenced by several factors which have a variable effect on the clinical picture. Unassociated thalassemias seem the most polymorphic. Although it seems that in certain foci the beta-thalassemias are fairly stereotyped, this first study shows in Algeria great heterogeneity. All forms are observed both clinically and in the laboratory. Present classifications have not supplied a sufficiently operative model. It is not doubt necessary to await further progress in the laboratory to classify these diseases more precisely.