Zaher K. Otrock

Meta-Analysis on the Use of Zidovudine and Interferon-Alfa in Adult T-Cell Leukemia/Lymphoma Showing Improved Survival in the Leukemic Subtypes

PURPOSE Human T-cell lymphotropic virus type-I-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive, chemotherapy-resistant malignancy. Multiple small studies using zidovudine (AZT) and interferon-alfa (IFN-α) have shown response in patients with ATL. However, the impact of this innovative antiviral treatment strategy on long-term survival remains undetermined. PATIENTS AND METHODS We report a meta-analysis of antiviral therapy of ATL. Medical records of 254 patients with ATL who were treated in the United States, the United Kingdom, Martinique, and continental France were individually reviewed. RESULTS According to Shimoyama classification, there were 116 patients with acute ATL, 18 patients with chronic ATL, 11 patients with smoldering ATL, and 100 patients with ATL lymphoma. In 231 patients with available survival data, first-line therapy was recorded in 207 patients. Five-year overall survival rates were 46% for 75 patients who received first-line antiviral therapy (P = .004), 20% for 77 patients who received first-line chemotherapy, and 12% for 55 patients who received first-line chemotherapy followed by antiviral therapy. Patients with acute, chronic, and smoldering ATL significantly benefited from first-line antiviral therapy, whereas patients with ATL lymphoma experienced a better outcome with chemotherapy. In acute ATL, achievement of complete remission with antiviral therapy resulted in 82% 5-year survival. Antiviral therapy in chronic and smoldering ATL resulted in 100% 5-year survival. Multivariate analysis confirmed that first-line antiviral therapy significantly improves overall survival of patients with ATL (hazard ratio, 0.47; 95% CI, 0.27 to 0.83; P = .021). CONCLUSION These results confirm the high efficacy of AZT and IFN, which should now be considered the gold standard first-line therapy in leukemic subtypes of ATL.

Thalassemia and hypercoagulability

Thalassemia is a congenital hemolytic disease caused by defective globin synthesis resulting in decreased quantity of globin chains. Although the life expectancy of beta-thalassemia patients has markedly improved over the last few years, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events, mainly in beta-thalassemia intermedia, has led to the identification of a hypercoagulable state in these patients. In this paper, we review the molecular and cellular mechanisms leading to hypercoagulability in beta-thalassemia, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemias. We also discuss the recommendations for thrombosis prophylaxis in these patients.

Clinical characteristics, prognostic factors, and outcomes of adult patients with hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by the activation of the mononuclear phagocytic system. The diagnosis of HLH in adults is challenging not only because the majority of the reported data are from pediatric patients, but also because HLH occurs in many disease entities. This study reports the clinical and laboratory findings and prognostic factors of adult HLH in a large cohort managed at a single medical center from 2003 to 2014. Seventy‐three patients met the HLH‐2004 diagnostic criteria. The median age was 51 years (range, 18–82 years); 41 (56.2%) were male. Patients manifested fever, cytopenias, and elevated ferritin in >85% of cases. Likely causes of HLH were as follows: 30 (41.1%) infections, 21 (28.8%) malignancies, 5 (6.8%) attributed to autoimmune disorders, 1 (1.4%) primary immunodeficiency, 2 (2.7%) post solid organ transplantation, and 13 (17.8%) idiopathic. The median overall survival was 7.67 months. Patients with malignancy‐associated HLH had a markedly worse survival compared with patients with non–malignancy‐associated HLH (median overall survival 1.13 vs. 46.53 months, respectively; P < 0.0001). In a multivariable analysis, malignancy (hazard ratio = 12.22; 95% CI: 2.53–59.02; P = 0.002) correlated with poor survival. Ferritin >50,000 µg/L correlated with 30‐day mortality. Survival after a diagnosis of HLH is dismal, especially among those with malignancy‐associated HLH. The development of a registry for adults with HLH would improve our understanding of this syndrome, validate diagnostic criteria, and help develop effective treatment strategies. Am. J. Hematol. 90:220–224, 2015.

Incidence of urinary tract infection following transrectal ultrasound guided prostate biopsy at a tertiary-care medical center in Lebanon

OBJECTIVE To determine the incidence of urinary tract infections (UTIs) following transrectal ultrasound guided needle biopsy of the prostate (TRUBP) and the bacteriology of these infections. DESIGN Retrospective evaluation of the charts and records of all patients who underwent TRUBP between June 1, 2002, and August 31, 2003. SETTING American University of Beirut Medical Center, a tertiary-care center in Lebanon. PATIENTS Two hundred seven patients underwent TRUBP. All received prophylactic antibiotics. One hundred twenty (58%) received ciprofloxacin alone, whereas 87 (42%) received both ciprofloxacin and gentamicin. Sixty-one patients (29.5%) had an enema prior to the procedure, whereas 146 (70.5%) did not. RESULTS Thirteen patients (6.3%) were admitted with UTI. All had rigors and fever on admission. Symptoms appeared at a mean of 2.7 days and the mean hospital stay was 9.2 days. The mean duration of antibiotic treatment was 23.2 days. Ten (77%) of the patients had positive bacteriology. Urine cultures were positive in 8 (61.5%) of the patients and blood cultures in 6 (46.2%). All positive cultures grew Escherichia coli resistant to ciprofloxacin, with 5 isolates producing extended-spectrum betalactamases. CONCLUSIONS TRUBP continues to be associated with significant infectious complications, especially UTI. Given the increasing incidence of antibiotic resistance mainly among the Enterobacteriaceae, antimicrobial prophylaxis practices should be reevaluated and the universal administration of quinolones alone or in combination with aminoglycosides should be reconsidered.

Hypoxia-inducible factor in cancer angiogenesis: Structure, regulation and clinical perspectives

Tumor hypoxia is a common feature of many cancers. A master regulator of hypoxic response is the transcription factor hypoxia-inducible factor-1 (HIF-1). It functions as a master regulator of oxygen and undergoes conformational changes in response to varying oxygen concentrations. In this paper, we review what has been described about HIF-1: its structure, its regulation and target genes, its role in cancer, and its implication for cancer therapy.

Expression, prognostic and predictive impact of VEGF and bFGF in non-small cell lung cancer.

Despite major advances in cancer therapeutics, the prognosis for lung cancer patients is still poor and the median survival for patients presenting with advanced non-small cell lung cancer (NSCLC) is only 8-10 months. Angiogenesis is an important biological process and a relatively early event during lung cancer pathogenesis. Anti-angiogenic agents are used in treating patients with NSCLC, and their molecular biomarkers are also being assessed to predict response. A better understanding of the biology of angiogenesis in NSCLC may reveal new targets for treating this malignancy. In this article, we review the expression and prognostic impact of the angiogenic growth factors, vascular endothelial growth factor and basic fibroblast growth factor, in NSCLC.

Apolipoprotein E Gene Polymorphism and Allele Frequencies in the Lebanese Population

Apolipoprotein E (ApoE) genotypes were studied in order to determine the prevalence in the Lebanese population and compare it with other populations. DNA from 160 unrelated healthy donors from our HLA-bank was used. ApoE genotype was determined using the CardioVascular Disease (CVD) StripAssay (this assay is based on a Polymerase Chain Reaction-Reverse Hybridization technique). The prevalence of genotypes E3/3, E3/4, and E2/3 was found to be 69%, 26%, and 22%, respectively, and 0.6% for each of E2/4 and E4/4 genotypes. The Lebanese population tested showed similarities to earlier reported ApoE genotypic distributions (high E3 allele frequency) but also peculiar differences especially to some Arabic countries (total absence of E2 allele among Saudis) and other populations. This is the first report from Lebanon that will serve as a template for future investigations of the prevalence of ApoE alleles in association with various clinical entities.

Angiotensin-converting enzyme gene polymorphism and allele frequencies in the Lebanese population: prevalence and review of the literature.

We studied the distribution of the D/D, I/D, and I/I genotypes of the angiotensin-converting enzyme (ACE) in a sample of healthy Lebanese individuals to assess their prevalence and compare them with other populations. ACE genotypes were determined using the Cardiovascular Disease (CVD) StripAssay, which is based on a Polymerase Chain Reaction-Reverse hybridization technique. DNA from 133 unrelated healthy donors from our HLA-bank was used. The prevalence of D/D, I/D, and I/I genotypes was found to be 39.1, 45.1, and 15.8% respectively, with D and I allelic frequency of 61.7 and 38.3%, respectively. The sampled Lebanese population showed ACE genotypic distributions similar to Caucasians; however, with tendency towards harboring high D allele frequency together with a low I allele frequency just like the Spanish population. This first report from Lebanon will serve as a baseline statistical data for future investigations of the prevalence of ACE genotypes in association with various clinical entities notably cardiovascular diseases. The medical literature was also reviewed in this context.

Prevalence of factor V R2 (H1299R) polymorphism in the Lebanese population.

Aims: A recently identified polymorphism in factor V gene (His1299Arg; also named HR2) has been reported to be a possible risk factor for the development of venous thromboembolism (VTE), with a high prevalence of 9.5–15.2% in patients of different ethnic groups in different parts of the world. The aim of this study is to assess the prevalence of HR2 haplotype in Lebanon. Methods: We randomly selected 125 samples from unrelated donors logged into our HLA registry; these represent healthy Lebanese individuals originating from different provinces and religious communities of the country. Their DNA was extracted using the Pel‐Freez extraction kit and stored at −80°C for later use. The CVD StripAssay was used for PCR and reverse hybridisation. It screens for several gene mutations including factor V H1299R. Results: A total of 125 controls were studied: 72 males and 53 females with a median age 42 years. Thirteen (10.4%) had the HR2 haplotype; 11 (8.8%) were heterozygous (R1/R2), and two (1.6%) were homozygous (R2/R2), with an allelic frequency of 0.06. Conclusions: Our study is the first report from Lebanon that describes the prevalence of HR2 haplotype and the frequency of its alleles. We are reporting a high prevalence of the HR2 in our population (10.4%). The hypothesis that A4070G polymorphism might contribute to the expression of a thrombotic phenotype deserves to be tested in our population through larger studies.

Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer.

BackgroundZoledronic acid is very widely used in patients with metastatic bone disease and osteoporosis. Only one case of bilateral uveitis was recently reported related to its use.Case presentationWe report the first case of severe unilateral anterior uveitis in a patient with breast cancer and an intraocular lens. Following zoledronic acid infusion, the patient developed severe and dramatic right eye pain with decreased visual acuity within 24 hours and was found to have a fibrinous anterior uveitis of moderate severity The patient was treated with topical prednisone and atropine eyedrops and recovered slowly over several months.ConclusionInternists, oncologists, endocrinologists, and ophtalmologists should be aware of uveitis as a possible complication of zoledronic acid therapy. Patients should be instructed to report immediately to their physicians and treatment with topical prednisone and atropine eyedrops should be instituted immediately at the onset of symptoms. This report documents anterior uveitis as a complication of zoledronic acid therapy. This reaction could be an idiosyncratic one but further research may shed more light on the etiology.