Balkis Meddeb
The Chinese University of Hong Kong
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Featured researches published by Balkis Meddeb.
Leukemia Research | 2010
Ramzi Jeddi; Héla Ghédira; Samia Mnif; Emna Gouider; Pierre Fenaux; Balkis Meddeb
Increased BMI has been correlated to an increased incidence of APL, but not to the occurrence of differentiation syndrome (DS) in APL. We consecutively treated 39 APL patients with ATRA and idarubicin (according to PETHEMA regimen). Median age was 26 years. Forty-one percent patients were classified as intermediate risk, and 59% as high risk according to Sanzs score. Thirty-three patients (85%) reached CR. Eleven of the 36 patients evaluable for DS (30.5%) developed this syndrome (severe in 7 cases, moderate in 4, and fatal in 3 cases) within a median of 12 days (range 3-23) of ATRA onset. Six of the 9 (66.6%) patients with BMI>or=30 developed DS vs. 5 of 27 (18.5%) with BMI<30 (p=0.012). Other predictors of DS in univariate analysis were: age>or=40 year (p=0.033), baseline WBC>or=20 x 10(9)/l (p=0.003), and creatinine>1.4 mg/dl (p=0.009). In multivariate analysis, BMI>or=30 remained an independent predictor of DS in addition to baseline WBC>or=20 x 10(9)/l.
Hematology | 2010
Ramzi Jeddi; Mériem Achour; Ramzi Ben Amor; Lamia Aissaoui; Walid Bouterâa; Karima Kacem; Raihane Ben Lakhal; Hela Ben Abid; Zaher Belhadjali; Amel Turki; Balkis Meddeb
Abstract Severe sepsis defined as infection-induced organ dysfunction or hypoperfusion abnormalities predispose to septic shock and increased mortality in neutropenic setting. We aimed at determining predictors of severe sepsis in neutropenic patients. Between 1 October and 31 December 2007, 41 patients (21 with acute myeloid leukemia, 19 with acute lymphoid leukemia and one with autologous stem cell transplantation for a mantle cell lymphoma) with chemotherapy-induced neutropenia (<0·5 × 109/l) lasting for more than 7 days were included in this study. The median age was 28 years (range: 3–58 years). All patients were on oral antibacterial (colistin and gentamicin) and anti-fungal (amphotericin B) prophylaxis. The first neutropenic febrile episode was treated with piperacillin/tazobactam and colistin IV; if the patient remains febrile at 48 h from the start of this first line of treatment, amphotericin B i.v. is added. Imipenem was introduced in the case of non-response and finally glycopeptides were introduced according to the IDSA criteria. Severe sepsis and septic shock are defined according to the criteria of the consensus conference of the ACCP/SCCM excluding the leukocyte count since all the patients were neutropenic. Ninety-four febrile episodes were observed: 27 microbiologically documented (28·7%), six clinically documented (6·3%) and 61 fever of unknown origin (65%). Microbiologically documented infections were: 13 Gram-negative organisms, 11 Gram-positive organisms and three combined (Gram+ and −). Clinically documented infections were pneumonia (two), neutropenic enterocolitis (one), sinuses infection (one) and cutaneous infection (two). Severe sepsis accounted for 22 febrile episodes. Factors associated with the occurrence of severe sepsis were: hypophosphatemia (<0·8 mmol/l; p=0·05, OR=3·9, 95% CI: 1·3–45·7), hypoproteinemia (<62 g/l; p=0·006, OR=4·1, 95% CI: 1·4–11·4) and non-adapted antibiotherapy at the onset of severe sepsis (p=0·019, OR=2·7, 95% CI: 1·02–7·39). However, heart rate/systolic blood pressure ratio <1·1 (p<0·001, OR=0·1, 95% CI: 0·03–0·31) and Creactive protein <80 mg (p=0·001, OR=0·14, 95% CI: 0·04–0·54) were not predictive.
Hematology | 2011
Ramzi Jeddi; Hela Ghedira; Ramzi Ben Amor; Amel Turki; Karima Kacem; Yosr Ben Abdennebi; Raihane Ben Lakhal; Lamia Aissaoui; Hela Ben Abid; Zaher Bel Hadjali; Balkis Meddeb
Abstract Pseudomonas is a clinically significant and opportunist pathogen, usually associated in causing high mortality nosocomial infections. The aim of this study was to determine the risk factors associated with septic shock in patients diagnosed with hematologic malignancies and Pseudomonas infections. A total of 80 Pseudomonas isolates (77 Pseudomonas aeruginosa) were collected from 66 patients aged 2–64 years: 52 with acute leukemia (79%), 7 with lymphoma (10·5%), and 7 with other hematologic disorders (10·5%), between 2001 and 2009. The median age of the patients was 30 years. Isolates were collected mostly from bloodstreams (45%) and skin lesions (31·5%). The median time for microbiologic documentation was 8 days (range 0–35 days) from onset of neutropenia. At least 11 patients (16·6%) had recurrent (⩾2) infections. The clinical symptoms observed were skin lesions (34%), diarrhea (20%), isolated fever (18%), and respiratory symptoms (14%). The isolates tested were found resistant to piperacillin/tazobactam (43%), ceftazidime (31%), imipenem-cilastatin (26%), ciprofloxacin (25%), and amikacin (26%). Septic shock occurred in 16·2% of episodes (13/80). Crude mortality due to septic shock occurred in 19·6% of patients (13/66). The median time for response to antibiotic therapy in the remaining 80·4% of patients (53/66) was 2·5 days. Univariate analysis revealed that factors associated with septic shock were: fever for ⩾3 days in patients on antibiotic therapy (P = 0·019), serum lactate >5 mmol (P = 0·05), hemoglobin level <50 g/l (P = 0·042), hypoproteinemia <50 g/l (P = 0·01), procalcitonin >10 ng/ml (P = 0·031), and hypophosphatemia (P = 0·001). Multivariate analysis revealed that hypophosphatemia (P = 0·018), hypoproteinemia (P = 0·028), and high serum lactate (P = 0·012) are significant factors, independently associated with increased risk of septic shock in patients with hematologic malignancies and Pseudomonas infections.
Turkish Journal of Hematology | 2014
Karima Kacem; Sami Zriba; Raihane Ben Lakhal; Walid Bouteraa; Lamia Aissaoui; Ramzi Ben Amor; Yosr Ben Abdennebi; Zaher Belhadj Ali; Hela Ben Abid; Balkis Meddeb
Primary non-Hodgkin’s lymphoma of the adrenal gland is rare. We report the case of a 56-year-old patient suffering from B symptoms. The CT scan showed a bilateral adrenal mass without any lymph nodes. Scan-guided biopsies led to the diagnosis of diffuse large B-cell lymphoma. The medullar biopsy eliminated a secondary lymphoma. The patient was treated by immunochemotherapy with a complete response before autologous stem cell transplantation.
Diagnostic Pathology | 2012
Hejer Elmahmoudi; Houssein Khodjet-El-Khil; Edvard Wigren; Asma Jlizi; Kaouther Zahra; Dorothé Pellechia; Christine Vinciguerra; Balkis Meddeb; Amel Ben Ammar Elggaaied; Emna Gouider
AbstractIntroductionHemophilia A is an X linked recessive hemorrhagic disorder caused by mutations in the F8 gene that lead to qualitative and/or quantitative deficiencies of coagulation factor VIII (FVIII). Molecular diagnosis of hemophilia A is challenging because of the high number of different causative mutations that are distributed throughout the large F8 gene. Molecular studies of these mutations are essential in order to reinforce our understanding of their pathogenic effect responsible for the disorder.AimIn this study we have performed molecular analysis of 28 Tunisian hemophilia A patients and analyzed the F8 mutation spectrum.MethodsWe screened the presence of intron 22 and intron 1 inversion in severe hemophilia A patients by southern blotting and polymerase chain reaction (PCR). Detection of point mutations was performed by dHPLC/sequencing of the coding F8 gene region. We predict the potential functional consequences of novel missense mutations with bioinformatics approaches and mapping of their spatial positions on the available FVIII 3D structure.ResultsWe identified 23 different mutations in 28 Tunisian hemophilia A patients belonging to 22 unrelated families. The identified mutations included 5 intron 22 inversions, 7 insertions, 4 deletions and 7 substitutions. In total 18 point mutations were identified, of which 9 are located in exon 14, the most mutated exonic sequence in the F8 gene. Among the 23 mutations, 8 are novel and not deposited in the HAMSTeRS database nor described in recently published articles.ConclusionThe mutation spectrum of Tunisian hemophilia A patients is heterogeneous with the presence of some characteristic features.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1693269827490715
Hematology | 2010
Ramzi Jeddi; Hela Ghedira; Samia Menif; Hend Ben Neji; Ramzi Ben Amor; Karima Kacem; Lamia Aissaoui; Walid Bouteraâ; Yosr Ben Abdennebi; Ben Lakhal Raihane; Emna Gouider; Hafsia Raouf; Ben Abid Hela; Ali Saad; Belhadjali Zaher; Balkis Meddeb
Abstract Acute promyelocytic leukemia (APL) has now become the most curable of all subtypes of acute myeloid leukemia. A cure rate of 75–80% can be anticipated with a combination of all-trans retinoic acid (ATRA) and anthracyclines. In Tunisia, the ATRA era began in 1998 with the use, consecutively, of two regimens of a combination of ATRA with anthracycline and cytarabine (APL93), and without cytarabine (LPA99). From 2004, 39 patients with confirmed APL either by t(15;17) or PML/RARA were treated by the PETHEMA LPA 99 trial. The rationale of this protocol by avoiding cytarabine is to reduce death in complete remission (CR) without increasing the incidence of relapse. Thirty-three patients achieved CR (84·6%). The remaining six patients were considered as failure due to early death: three caused by differentiation syndrome (DS) and three died from central nervous system hemorrhage. Baseline blood cell count (WBC) >10 × 109/l (P=0·26) and creatinine >1·4 mg/dl (P=0·42) were not predictive of mortality. DS was observed in 11 patients (30·5%) with a median onset time of 12 days (range: 3–23 days) and median WBC of 29 × 109/L (range: 1·2 × 109–82·7 × 109/l). DS was severe in seven cases, moderate in four, and fatal in three cases. Body mass index ≥30 (P=0·044) and baseline WBC ≥20 × 109/l (P=0·025) are independent predictors of DS. The median follow-up of this study is 36 months. Thirty patients are alive in continuous complete remission; two patients died in CR from septic shock and secondary myelodysplastic syndrome respectively; one patient died 47 months after achieving two relapses. Event free survival from diagnosis was 80% and overall survival was 82%. Our results are quite acceptable and can be improved by reducing mortality rate.
Haematologica | 2018
Anne-Sophie Michallet; Melih Aktan; Wolfgang Hiddemann; Osman Ilhan; Peter Johansson; Kamel Laribi; Balkis Meddeb; Carol Moreno; João Raposo; Anna Schuh; Ali Unal; Tom Widenius; Alf Bernhardt; Kerstin Kellershohn; Dimitri Messeri; Stuart Osborne; Véronique Leblond
MABLE investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabine-ineligible patients with chronic lymphocytic leukemia. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Rituximab plus chlorambucil-treated patients without a complete response after Cycle 6 received chlorambucil monotherapy for at least six additional cycles or until complete response. The primary endpoint was complete response rate (confirmed by bone marrow biopsy) after Cycle 6 in first-line patients. Secondary endpoints included progression-free survival, overall survival, minimal residual disease, and safety. Overall, 357 patients were randomized (rituximab plus bendamustine, n=178; rituximab plus chlorambucil, n=179; intent-to-treat population), including 241 first-line patients (n=121 and n=120, respectively); 355 patients received treatment (n=177 and n=178, respectively; safety population). In first-line patients, complete response rate after Cycle 6 (rituximab plus bendamustine, 24%; rituximab plus chlorambucil, 9%; P=0.002) and median progression-free survival (rituximab plus bendamustine, 40 months; rituximab plus chlorambucil, 30 months; P=0.003) were higher with rituximab plus bendamustine than rituximab plus chlorambucil. Overall response rate and overall survival were not different. In first-line patients with a complete response, minimal residual disease-negativity was higher with rituximab plus bendamustine than rituximab plus chlorambucil (66% vs. 36%). Overall adverse event incidence was similar (rituximab plus bendamustine, 98%; rituximab plus chlorambucil, 97%). Rituximab plus bendamustine may be a valuable first-line option for fludarabine-ineligible patients with chronic lymphocytic leukemia.
Diagnostic Pathology | 2012
Hejer Elmahmoudi; Fatma Ben-lakhal; Wijden Elborji; Asma Jlizi; Kaouther Zahra; Rim Sassi; Moez Zorgan; Balkis Meddeb; Amel Elgaaied Ben Ammar; Emna Gouider
Inherited factor VII (FVII) deficiency is a rare disorder characterized by a bleeding phenotype varying from mild to severe. To date, more than 200 mutations have been described along the F7 gene encoding for FVII. The aim of this study was the identification of genetic defects underlying FVII deficiency in 10 patients belonging to eight unrelated families of the North provinces from Tunisia. Mutation detection was performed by sequencing the whole F7 gene coding region, exon-intron boundaries and about 400 bp of the promoter region. We identified 5 mutations in five unrelated families; the novel p.F328Y mutation and the reported mutations: p.R304Q, p.M298I, IVS1aG > A and p.G-39G. For the remaining 5 patients we didn’t identified any mutations using PCR/Sequencing protocol. In conclusion, this study represents the first comprehensive molecular series of FVII deficiency affected patients in Tunisia from the North. We will try in the future to continue the molecular study for Tunisian patients from Center and South provinces in order to have a complete idea about the FVII deficiency mutational profile in our country.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1288044089753085
Medical Oncology | 2011
Ramzi Jeddi; Hela Ghedira; Ramzi Ben Amor; Samia Menif; Zaher Belhadjali; Balkis Meddeb
Differentiation syndrome (DS) is a life-threatening complication observed in patients with acute promyelocytic leukemia (APL) receiving induction therapy with all-trans-retinoic acid (ATRA). A bimodal incidence of DS has been observed, with a majority of cases occurring during the first week of ATRA treatment (“early” DS), but a substantial number of cases occurring during the third or even fourth week of ATRA treatment (“late” DS). However, to our knowledge occurrence of both early and late DS in the same patient has not been reported. We report an APL patient treated with the AIDA regimen, who experienced both early and late DS, a situation where differential diagnosis was difficult.
Haemophilia | 2012
Hejer Elmahmoudi; A. Chalbi; F. Ben-Lakhal; W. Borji; Kaouther Zahra; M. Zorgan; Balkis Meddeb; Emna Gouider
is unlikely that the occurrence of secondary PPH was recorded. Most cases of secondary PPH are dealt within the community or in the emergency setting and therefore a different approach is required to identify its true incidence. Previous case series reported higher risk of secondary PPH in women with VWD [3,6]. The use of pictorial blood loss assessment chart to quantify puerperal loss has demonstrated that women with bleeding disorders have longer duration of lochia (39 days, range 21–58 days) compared with women without a bleeding disorder (31 days, range 10–62 days) P = 0.03 [9]. There is insufficient data on the factor levels in the affected women; among 24 women with type 1 VWD included in the study, at least three had levels above 50 IU dL . It is possible that some of the women included in the study only had borderline levels or very mildly reduced levels and thus not a confirmed diagnosis of VWD. The authors have cited the rise in von Willebrand factor (VWF) and factor VIII (FVIII) levels that occur during pregnancy as an explanation for VWD posing no significant increased risk of primary PPH. In general, patients with type 1 VWD show an increase in their VWF and FVIII levels during pregnancy. Although most women achieve factor levels >50 IU dL 1 by full term, some cases of type 1 VWD have insufficient correction in the haemostatic defect [10], especially those with factor levels that are more than mildly reduced [5]. In type 2A VWD, VWF antigen may increase in pregnancy, but its activity remains unchanged. There may also be worsening thrombocytopaenia in type 2B, and those with type 3 VWD show no increase in their factor levels. Therefore, clinician should be vigilant when managing women with VWD in pregnancy and avoid complacency and reliance on improvements of the coagulation defect. An individualized assessment of the bleeding risk prior to delivery and careful planning for an appropriate haemostatic cover during delivery and postpartum period are essential to reduce the risk of PPH. In summary, it is clear from other studies already published in the literature that the risk of PPH and other bleeding complications are higher in women with VWD. Although the authors of this study state that they found no evidence that women with VWD have a significantly increased risk of PPH, a close look at their findings show higher risk of PPH in VWD and significant increase in the risk for those with confirmed diagnosis before pregnancy.