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Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression changes may influence IM response. In this study, we aimed to investigate the impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the clinical outcome in CML patients. hOCT1 expression profile was determined using the quantitative real-time polymerase chain reaction in 69 CML patients treated with IM (35 responders to IM patients and 34 IM-resistant patients), while genotyping of 69 cases and 51 controls for hOCT1 polymorphisms was performed by direct sequencing after amplification of exon7. Our results showed that the hOCT1 gene was significantly downregulated in the samples of the IM-resistant group when compared with the IM-responder group (p = 0.0211). Moreover, sequencing data show an association in all cases between the SNP 408V>M (g.1222G>A) and an intronic 8 bp (base pairs) insertion of GTAAGTTG (rs36056065) at the 3′ end of exon 7. The genotype and allele distribution of the different SNPs did not differ significantly between the two groups of patients. hOCT1 mRNA expression may serve as a clinical biomarker of response to imatinib and could be useful to predict IM therapy outcome of CML patients.

International audience; Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome-overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)-were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3-85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3-51), 18 months (3-72), and 24 months (3-100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) were 81, 90, and 90%, respectively. By multivariate analysis, AP, high EUTOS risk, and baseline WBC ≥ 150G/l remained independent predictive factors of non-optimal response to IM. The adverse events (AE) of IM were moderate and tolerable. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The frontline use of second-generation tyrosine kinase inhibitor (TKI) is expected to improve the results of the first-line treatment of these high-risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries.

Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patient and conservative treatment was attempted in the other patient. None treatment measures were effective and two patients died. Acute acalculous cholecystitis is a serious complication in neutropenic patients. Earlier diagnosis could have expedited the management of these patients., Highlights • Acute acalculous cholecystitis has rarely described in patients undergoing myelosuppressive chemotherapy for acute myeloblastic leukemia. • Acute acalculous cholecystitis associated with poor short term outcome in neutropenic patients. • Acute acalculous cholecystitis should be added to be the causes of acute abdominal pain in neutropenic patients and unexplained fever. • Earlier diagnosis can improve the prognosis of Acute acalculous cholecystitis during chemotherapy for AML.

As the number of web services is increasing, finding the best service according to the users' requirements becomes a challenging task. Traditional method of web services discovery is based on keyword match. Due to this, many web services which are most relevant to the user request are left undiscoverable. Some other emergent approaches for discovering web services are based on semantics which improves the quality of the discovered web services in terms of relevance and satisfaction of user's need. In this paper, we briefly discuss the challenges facing semantic web services discovery and present different approaches for this process. We present also our proposed algorithm that aims to help users in the process of selection of the most appropriate semantic web service.

Resume Introduction L’anemie de Fanconi (AF) est une maladie hereditaire caracterisee par une heterogeneite genetique et phenotypique. De nombreux groupes ont mis en place des registres propres a leur pays. En Tunisie, le groupe tunisien d’etude de l’AF (GETAF) a cree le registre tunisien de l’AF « TFAR ». Patients et methodes Tous les services d’hematologie et de pediatrie de Tunisie ont ete contactes pour inclure leurs malades diagnostiques entre janvier 1983 et decembre 2008. Le registre TFAR a ete integre dans le site web du groupe GETAF a l’adresse : www.fanconi-tunisie.net . Resultats Le tri des fiches a permis de retenir 142 patients appartenant a 118 familles. L’âge median de diagnostic etait de 11 ans. Une consanguinite etait notee dans 86 % des cas, un syndrome malformatif dans 91 %, une pancytopenie au moment du diagnostic dans 69 %. Parmi 28 patients, 95 % appartenaient au groupe FANCA. Cent neuf patients etaient traites par androgenes et 27 avaient eu une allogreffe de moelle osseuse geno-identique. Un syndrome myelodysplasique (SMD) avait ete diagnostique dans 4 % des cas, une leucemie aigue (LA) dans 6 % et une tumeur solide dans 2 % des cas. L’âge median de survie etait de 17 ans et 5 mois, il etait significativement meilleur chez les patients allogreffes. Conclusion L’AF parait frequente en Tunisie. L’atteinte hematologique est la circonstance de decouverte la plus frequente. Elle est souvent moderee ou severe et necessite un traitement par androgenes ou allogreffe de moelle osseuse. Celle-ci devrait concerner tous les patients ayant un donneur familial HLA-compatible.

Resume Le plasmocytome est une tumeur maligne qui derive des plasmocytes ; sa localisation ovarienne est exceptionnelle ; nous rapportons un cas de plasmocytome ovarien bilateral diagnostique en postoperatoire ; il n’y avait pas de gammapathie monoclonale, ni lyse osseuse et la biopsie osteomedullaire etait normale. La patiente avait recu une radiotherapie postoperatoire ; elle est sans rechute avec un recul de six mois.

The occurrence of an isolated ovarian or pelvic relapse of acute lymphoblastic leukemia (ALL) in complete remission after chemotherapy has rarely been described. We report the case of a 12-year-old girl, treated for ALL, who developed an isolated left ovarian and fallopian tube localization without medullary or blood relapse 4 years after the end of the initial treatment. She presented with an isolated pelvic mass. The diagnosis was established by a CT-guided biopsy. The treatment consisted of a second course of chemotherapy and complementary surgery; a second complete remission was obtained.

Resume Objectif de l’etude Evaluer les resultats therapeutiques des lymphomes gastriques localises agressifs de pronostic favorable apres chimiotherapie et radiotherapie. Patients et methodes Entre fevrier 1993 et decembre 2004, neuf patients atteints de lymphome gastrique primitif localise de haut grade ont ete pris en charge par le comite lymphome du centre hospitalier universitaire de Sfax (Tunisie). Le sex-ratio etait 1,5 et l’âge moyen de 44,9 ans. Le type histologique etait un lymphome B a grandes cellules dans 100 % des cas. La maladie etait selon la classification d’Ann Arbor modifiee de stade IE dans huit cas et de stade IIE dans un cas sans aucun facteur de pronostic defavorable. Le traitement a consiste en une chimiotherapie suivie d’une radiotherapie de l’estomac avec ou sans les aires ganglionnaires perigastrique a la dose de 40 Gy. Resultats A la fin du traitement, tous les patients etaient en situation de remission complete. Avec un recul moyen de 55,7 mois, un patient a ete perdu de vue, les autres etaient en vie en situation de remission complete. Aucune toxicite aigue majeure n’a ete rapportee. Au cours du suivi, aucun patient n’a souffert de toxicite tardive. Le taux de survie globale a cinq ans etait de 100 %. Conclusion L’association de radiotherapie et de chimiotherapie peut etre proposee pour les lymphomes gastriques localises de pronostic favorable, vu les resultats tres satisfaisants en termes de controle de la maladie et de tolerance.

Resume Introduction Les immunosuppresseurs sont habituellement indiques dans le traitement de premiere ligne des formes non severes de l’aplasie medullaire acquise (AMA). Le but de ce travail etait d’evaluer l’efficacite d’un protocole prospectif associant la ciclosporine aux androgenes dans le traitement des AMA non severes de l’adulte. Methodes Vingt-neuf cas diagnostiques et suivis a Sfax ont ete inclus sur une periode de dix ans (1991–2000). Mis a part le traitement symptomatique, tous nos patients ont recu un traitement specifique comportant une bitherapie a base de ciclosporine a la dose de 5 mg/kg par jour et des androgenes a la dose de 0,5 mg/kg par jour. Resultats Les taux de reponses a trois mois, a six mois et a 12 mois sont respectivement de 48, 75 et 87 %. Les taux de survies sont de 52 % a un an et de 37 % a cinq et dix ans. Les principales toxicites etaient hepatiques et renales ainsi que l’hypertension arterielle, qui ont ete observees chez respectivement 53, 16 et 15 % des patients avec une reversibilite respective dans 65, 87 et 100 % des cas. Conclusion Les taux de reponse et de survie dans notre serie sont assez satisfaisants comparativement a ceux obtenus par les immunosuppresseurs (serum antilymphocytaire et ciclosporine) dans la litterature. L’association des androgenes a permis de potentialiser l’immunosuppression induite par la ciclosporine mais au prix d’effets secondaires plus importants.

Factor XIII deficiency is a rare autosomal recessive congenital disorder of haemostasis characterised by a plasmatic factor XIII level less than 1% in homozygote and bleeding as of the youth. We report a study about ten patients with congenital factor XIII deficiency from seven south-Tunisian families, there are seven females. Umbilical bleeding was common and only two patients had intracranial bleeding. The standard screening tests are normal. Factor XIII activity was less than 1% in all patients. A sub-unit A deficit was detected for the ten patients. Out hemorrhagic context, five patients receive regular prophylactic transfusion with fresh frozen plasma.

Geotrichum capitatum is an uncommon cause of invasive infections in immunocompromised patients, particularly those with hematological malignancies and severe neutropenia. The aim of this study was to report the cases of invasive geotrichosis in our hospital. It is a retrospective study of invasive geotrichosis diagnosed in the Laboratory of Parasitology–Mycology of the UH Habib Bourguiba, Sfax, from January 2005 to August 2013. Six cases of invasive Geotrichum infections were diagnosed. There were three men and three women. The mean age was 35 years. Five patients have acute myeloid leukemia with a profound neutropenia, and one patient was hospitalized in the intensive care unit for polytraumatism. Clinically, the prolonged fever associated with pulmonary symptoms was the predominant symptom (n = 5). Geotrichum capitatum was isolated in one or more blood culture. Two patients had urinary tract infections documented by multiple urine cultures positive for G. capitatum. Five patients received conventional amphotericin B alone or associated with voriconazole. The outcome was fatal in four cases. Invasive geotrichosis is rare, but particularly fatal in immunocompromised patients. Approximately, 186 cases have been reported in the literature. The prognostic is poor with mortality over 50 %. So, early diagnosis and appropriate management are necessary to improve prognosis.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in profoundly neutropenic patients. Delayed diagnosis and therapy may lead to poor outcomes. Aims The objective of this study was to assess the performance characteristics of the galactomannan (GM) assay in serum and bronchoalveolar lavage specimens for the diagnosis of IA in neutropenic patients with hematological malignancies. We also evaluated the prognostic outcome. Patients and methods A total of 1198 serum samples and 42 BAL from 235 neutropenic patients were tested with a GM elisa platelia test. We used Cox modeling of time to 6- and 12-week mortality for GM level at the time of diagnosis (GM0) and GM decay in the week following diagnosis in proven and probable IA patients with more than two GM values. Results There were three proven, 55 probable, and four possible cases of IA. The sensitivity and specificity of the GM test were 96.8% and 82.4% respectively. In BAL samples, sensitivity was 86% and the specificity 93%. BAL GM was more sensitive than microscopy (22.2%) and BAL culture (38.9%). Among patients with proven/probable IA, serum and BAL GM were in agreement for 92.8% of paired samples. The hazard ratio (HR) of GM0 and 1-week GM decay per unit increase in Aspergillus enzyme immunoassay (EIA) was 1.044 (95% CI, 0.738 to 1.476) and 0.709 (95% CI, 0.236 to 2.130) respectively. Conclusion We found good correlation between the GM0 and GM decay combination and outcome of IA patients. The GM is a useful tool for diagnosis and monitoring of IA.

Background The introduction of the first targeted tyrosine kinase inhibitor (TKI), imatinib mesylate (IM) revolutionized the therapeutic paradigm and dramatically improved outcomes of chronic myeloid leukemia(CML). Data are limited in developing countries regarding the clinicopathologic features and response to therapy in the era of IM. Aims To report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400mg daily as frontline therapy and to determine imatinib’s efficacy and safety. Methods From October 2002 to December 2011, two hundred and ninety two CML patients were treated with IM in 6 Tunisian departments of hematology. Monitoring response was defined as the ELN provided guidelines. Response (Hematologic, cytogenetic and molecular responses), adverse events and outcome (overall survival, event free survival and progression free survival) were evaluated. The factors associated with outcome of IM therapy were also analyzed. Results Two hundred ninety-two patients enrolled with a median follow-up duration of 56 (8 -290) months: The median age was 44 years (3-78 years). One hundred and fifty (51.3%) patients were male, 134 (49%) were asymptomatic at diagnosis. Splenomegaly was present in 237 of 292 (81%). Additional cytogenetic abnormalities were encountred in 24 (8.3%) patients. At diagnosis, 271 (92.8%) patients were in CP, 21 (7.2%) were in AP. The Sokal risk was low in 64 (23%), intermediate in 94 (33.5%), and high in 122 patients (43.5%). The Eutos risk was low in 179 (75%), and high in 60 (25%) patients.The rate of cumulative complete hematologic response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR) and molecular response 4/5 log (CMR) in CP/AP CML patients were 93.8%, 73%, 65% and 33.9%, respectively. According to the 2009 ELN criteria, optimal, suboptimal response and failure were noted in 132 (47%), 68 (24%) and 82 (29%) patients, respectively. Five year event free survival (EFS), progression free survival (PFS) and overall survival (OS) were 78%, 89% and 91%, respectively. By multivariate analyzis, AP, high Eutos risk and baseline WBC ≥ 150G/l remained independent predictive factors of non optimal response to IM. AP was an adverse independent prognostic factor for EFS, PFS and OS. Patients obtained CCyR at 12 months after the initiation of IM treatment were associated with longer PFS (P< 0.0001) and OS (P< 0.0001). ELN response was also significantly associated with EFS. The adverse events (AE) of IM were moderate and tolerable. Only 3 patients discontinued IM for intolerance. IM-related hematologic AE included neutropenia in 6.2%, anemia in 8.9%, and thrombocytopenia in 17.2%. Nonhematologic AE (21%), including mainly edema in 7.1%, digestive disorders in 5.5%, weight gain and skin rash in 3.1%. Conclusion We found that substantial number of patients in our series were in intermediate or high risk group. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The front-line use of 2nd TKI are expected to improve the results of the first line treatment of these high risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries. Disclosures: No relevant conflicts of interest to declare.

Introduction The aim of the study is to evaluate the treatment results of localised aggressive gastric lymphomas with favourable prognostic using chemotherapy and radiotherapy. Methods Between February 1993 and December 2010, 12 patients with primary gastric high grade lymphoma have been treated by the lymphoma comity of Sfax (Tunisia). The sex ratio was 1, 5. The mean age was 47 years (33-63). Histological type was the large cell B lymphoma in 100% of cases. Disease was stage I in 11 cases and stage II in 1 case (Ann Arbor Classification). The treatment consisted on primary chemotherapy followed by radiotherapy of stomach with or without regional nodes (40Gy). Results After treatment al patients had complete remission. With a mean follow up of 72 months, 3 patients were lost to follow up; the other patients were alive with complete remission. No major acute toxicities or late effects were found. Overall survival was 100% at 5years. Conclusion Chemotherapy associated with radiotherapy can be proposed to patient having localised and aggressive primary gastric lymphoma with favourable prognostic since this treatment is well tolerated and it provide satisfactory control of the disease.