[Show abstract][Hide abstract] ABSTRACT: ABSTRACT: Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein.
Hereditary Cancer in Clinical Practice 09/2011; 9(1):9. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction. Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion in HES supports the diagnosis of chronic eosinophilic leukemia (CEL) and provides a molecular explanation for the pathogenesis of this disorder. We screened seven Tunisian patients fulfilling the WHO criteria of HES for the presence of the FIP1L1-PDGFRA fusion gene using nested reverse transcription polymerase chain reaction on peripheral blood samples. Four of the seven patients were positive for this fusion gene. Sequence analysis revealed a substantial heterogeneity of the fusion transcripts due to the involvement of several FIP1L1 exons. All patients were male. The median age at diagnosis was 24 years (range, 18-50); one patient had a history of hypereosinophilia of more than 10 years. Two patients had clinically important and symptomatic eosinophilic endomyocardial disease with thrombotic events. Splenomegaly was constant in FIP1L1-PDGFRA positive CEL but not in the other HES patients (only 1/3).
[Show abstract][Hide abstract] ABSTRACT: Clonal rearrangement of antigen receptor genes is commonly used to characterize the lymphoproliferative diseases. In order to perform molecular characterization in the diagnostics and monitoring of lymphoid malignancies, leukemias and lymphomas in Tunisia, we have introduced the use of chemiluminescent probes for immunoglobulin (IG) and T cell receptor (TR) gene rearrangement detection employing the Southern blot method. The chemiluminescent and radioactive detection methods tested with alkaline phosphatase and 32P labelled probes, respectively, were used for the IG and TR gene rearrangement characterization. Our results show the same pattern of rearrangement. Moreover, the chemiluminescent signal is detected faster and it is as sensitive as the radioactive one. We report the optimized conditions for using IGH, IGK, IGL, TRB and TRG probes in non radioactive detection. We have applied the chemiluminescent Southern blot method to analyze examples of Tunisian leukemias and lymphomas. The results allowed the assessment of clonality and the T or B cell lineage of these cases. The use of non radioactive probes makes chemiluminescent Southern blot detection reliable, safe and sensitive. As the use of radioactivity is not common in our laboratories and the licensing requirements needed for its use prohibitive, the chemiluminescent technique will be of great help for detection and characterization of molecular markers in lymphoid malignancies in Tunisia.
Leukemia and Lymphoma 07/2006; 47(6):1129-37. · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thalidomide-dexamethasone therapy was given in patients (<61 years) with previously untreated symptomatic multiple myeloma. The aim of this study was to assess the efficacy and toxicity of this combination as first-line therapy, and to determine its effect on stem cell collection and engraftment. During first-line therapy, thalidomide and dexamethasone were administered for 75 days (200 mg/day) and 3 months, respectively. The monthly dose of dexamethasone was 20 mg/m2/day for 4 days, with cycles repeated on days 9 to 12 and 17 to 20 on the first and the third month of therapy. After first-line therapy, a collection of peripheral blood stem cells (PBSC) was performed. Between May 2003 and September 2004, 60 patients were included. On an intent-to-treat basis, the overall response (> or =partial response) rate was 74%, including 24% of patients who obtained a complete remission. Grade 3-4 toxicities consisted of infections (12%), deep-vein thrombosis (3%), constipation (5%), and neuropathy (5%). A total of 58 patients (96%) proceeded to PBSC mobilisation and yielded a median number of 8 x 10(6) CD34+ cells/kg. First-line thalidomide-dexamethasone therapy is effective and relatively well tolerated in young patients with symptomatic multiple myeloma. This combination does not affect PBSC mobilisation.
Bone Marrow Transplantation 09/2005; 36(3):193-8. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Geotrichum capitatum septicemias are rare, occurring exclusively in immunocompromised patients. We report a case of a 55-year-old man with acute myeloid leukemia who developed a G. capitatum septicemia with lung and skin lesions in the post chemotherapy aplasic phase. Treatment with amphotericin B (cumulative dose of 2 g) and maintenance with itraconazole resolved the clinical and radiological manifestations and controlled reactivation of the infection during the subsequent courses of cytotoxic chemotherapy. The emerging role of G. capitatum as an opportunistic agent in immunocompromised patient is stressed.
Journal De Mycologie Medicale - J MYCOLOGIE MEDICALE. 01/2005; 15(4):242-246.
[Show abstract][Hide abstract] ABSTRACT: Invasive pulmonary aspergillosis (IPA) remains a life threatening complication in immuno-compromised and especially in neutropenic patients. We report our experience in the diagnosis and therapeutic management of IPA in 8 patients with acute leukemia. All patients were neutropenic (PNN < 100/mm3, mean duration = 37 days) when IPA was diagnosed. Clinical signs included fever above 39 degrees and cough in all cases, chest pain in 4 cases, hemoptysis in 3 cases, rales in 5 cases. Chest x ray showed one lesion in 4 cases and multiple lesions in 4 cases. The diagnosis of IPA was established by bronchoalveolar lavage (BAL) in 5 cases, tissue biopsy in one case, positive sputum in one case and it was highly probable in one case. Thoracic computed tomographic (CT) scans were preformed after diagnosis confirmation of IPA and showed one or multiple lesions with air crescent signs. Serological tests were positive in 4 cases late in the course of IPA. All patients were treated with i.v. Amphotericin B. Outcome was favorable in 5 cases and three patients died by massive hemoptysis (in two cases) and systemic aspergillosis (in one case). Early diagnosis and appropriate treatment are essential to improve IPA prognosis.
[Show abstract][Hide abstract] ABSTRACT: Second malignant neoplasms are a major cause of late morbidity and mortality following treatment for Hodgkin's disease. Gastric carcinoma belong to the rare secondary malignancies induced by radiation-therapy and it is associated with a poor prognosis. We report a patient treated for Hodgkin's disease by 6 ABVD and total lymphoid radiation therapy, who developed a gastric carcinoma 9 years after completing treatment. Our case fits the criteria for radiation induced malignancies reported from the literature: In conclusion: recommendations are presented for both prevention and early detection of the tumours we recommend a strict follow-up for patients treated for HD to detect second cancers.
[Show abstract][Hide abstract] ABSTRACT: Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder characterized by severe thrombocytopenia due to the absence of bone marrow megakaryocytes. The pathogenic mechanisms of this disorder have not well defined; consequently, several empirical therapies are used. We reported the case of a 38-year-old mean who was hospitalized for serious bleeding syndrome. The platelet count was 10 yen10(9)/L. The bone marrow aspirate and biopsy showed the absence of megakaryocytes but otherwise normal granulocyte and erythroid precursors. No definable etiology has been found. After the unsuccessful use of prednisone, intravenous immunoglobulin therapy was started and resulted in favorable reponse.
Annales de medecine interne 06/2000; 151(3):223-6.
[Show abstract][Hide abstract] ABSTRACT: The precision of immunological characterization of leukemias was improved by a certain number of technical innovations, particularly hybridoma production and standardization, resulting in monoclonal antibodies and definition of recognised cellular antigens (designated by CD: Cluster of Differentiation). The aim of this work was to determine the immunophenotyping profile of patients with leukemia, by means of a flow cytometric method: 66 blood samples coming from leukemic persons in the Sahel region were studied by flow cytometry, using about thirty monoclonal antibodies all marked with a fluorochrome, in one or two colour systems to assess their distribution according to type (lymphoid B or T / myeloid) and age, and to search for possible co-expressions of markers of different lineages. The marked preponderance of childhood B-ALL in our series is, at least partly, attributable to the age distribution of the Tunisian population. In agreement with studies from other countries, the majority of AML cases occurred among adults. A high proportion of AML cases in our series co-expressed markers of other lineages. Overall, accurate classification of acute leukemias was possible from a simple peripheral blood sample in 62 of 66 cases (93.9%).
[Show abstract][Hide abstract] ABSTRACT: This study aims to identify the presenting symptoms, treatment and outcome of patients with nasal natural killer T (NK/T)-cell lymphoma and to find possible differences in survival based on Ann-Arbor stage and international prognostic index (IPI).
Computed tomography and biopsy results of 23 patients (15 males, 8 females; mean age 41 years; range 22 to 72 years) with extranodal NK/T-cell lymphoma who were treated at the department of clinical hematology between 1995 and 2011 were retrospectively analyzed.
The median time from onset of clinical symptoms to histological diagnosis was five months. Most patients presented with nasal obstruction (69%) and rhinism (52%). The site of extranodal NK/T-cell lymphoma primarily involved nasal cavity in 39%. Orbital extension was observed in 26%. Lymphomas were classified as stage IE in 30.4%, stage IIE in 47.8% and stage IVE in 21.7%. Nineteen patients received treatment: 10 received chemotherapy plus radiotherapy, nine received chemotherapy only. We used several regimens of chemotherapy including some protocols containing etoposid, L-asparaginase and others without this drugs. Univariate analysis showed that lower IPI score, low Ann-Arbor stage and responsiveness to treatment with both chemotherapy and radiotherapy were significant factors influencing both OS and PFS.
Nasal type NK/T-cell lymphoma showed a poor response to the conventional anthracycline-based chemotherapy, thereby an investigation for a novel therapy is urgently needed to improve survival.
Kulak burun bogaz ihtisas dergisi: KBB = Journal of ear, nose, and throat 22(5):275-83.