Incidence and characteristics of HBV reactivation in hematological malignant patients in south Egypt

AIM:To investigate characteristics of hepatitis B virus(HBV)implicated in HBV reactivation in patients with hematological malignancies receiving immunosuppressive therapy.METHODS:Serum samples were collected from 53 patients with hematological malignancies negative for hepatitis B surface antigen(HBsAg)before the start of and throughout the chemotherapy course.HBV reactivation was diagnosed when the HBsAg status changed from negative to positive after the initiation of chemotherapy and/or when HBV DNA was detected by realtime detection polymerase chain reaction(RTD-PCR).For detecting the serological markers of HBV infection,HBsAg as well as antibodies to the core antigen(antiHBc)and to the surface antigen were measured in the sera by CEIA.Nucleic acids were extracted from sera,and HBV DNA sequences spanning the S gene were amplified by RTD-PCR.The extracted DNA was further subjected to PCR to amplify the complete genome as well as the specific genomic sequences bearing the enhancerⅡ/core promoter/pre-core/core regions(nt1628-2364).Amplicons were sequenced directly.RESULTS:Thirty-five(66%)of the 53 HBsAg-negative patients were found to be negative serologically for antiHBc,and the remaining 18(34%)patients were positive for anti-HBc.Five of the 53(9.4%)patients with hematologic malignancies experienced HBV reactivation.Genotype D1 was detected in all five patients.Four types of mutant strains were detected in the S gene product of HBV strains and were isolated from 3 patients with HBV reactivation:T/S120,L143,and I126.HBV DNA was detected in the pretreatment HBsAg-negative samples in one of the five patients with HBV reactivation.In this patient,sequences encompassing the HBV full genome obtained from sera before the start of chemotherapy and at the time of de novo HBV hepatitis were detected and it showed 100%homology.Furthermore,in the phylogenetic tree,the sequences were clustered together,thereby indicating that this patient developed reactivation from an occult HBV infection.CONCLUSION:Past infection with HBV is a risk factor for HBV reactivation in Egypt.Mandatory anti-HBc screening prior to chemotherapy in patients with hematological malignancies is recommended.

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt

AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus(HBV) infections in patients with hematological malignancies in South Egypt.METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen(HBs Ag), and antibodies to HBV core(anti-HBc) and surface antigens. Serum samples negative for HBs Ag and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS HBV DNA was detected in 23(42.6%) of 54 patients with hematological malignancies who were HBsA g negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120 T and S143 L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsA g was detected by chemiluminescence enzyme immunoassay(CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143 L mutation despite the similar levels of extracellular and intracellular HBs Ag detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120 T and S143 L mutations. 120 T mutation impairs the detection of HBsA g by CLEIA.

Prolonged Infusion of Low Dose Gemcitabine in Advanced Pancreatic Carcinoma

Background: Gemcitabine was established as a monotherapy or in combination for locally advanced or metastatic pancreatic carcinoma. Aim: This study aimed to evaluate the efficacy of the low-dose gemcitabine over 6-hour infusion in patients with advanced pancreatic adenocarcinoma. Methods: 26 patients with locally advanced or metastatic pancreatic carcinoma were recruited into the study from December 2013 to October 2014. Patients received the treatment in Clinical Oncology Department, Sohag University, and Medical Oncology Department, Assiut University. Patients received low-dose gemcitabine (250 mg/m2) over 6-hour infusion, weekly for seven weeks and then on days 1 and 8 every 3 weeks till unacceptable toxicity or progression of the disease. Results: Twenty-six patients were enrolled in this study. After starting 7 weeks of treatment, the disease control rate was 38.5% in the form of complete response in 3.8% of patients, partial response in 26.9%, and stationary response in 7.7%. However, disease progression occurred in 61.5%. Progression-free survivals were 65.38%, 23.07%, 7.69% and 3.84% after 3, 6, 9 and 12 months, respectively. Also, overall survivals at 3-month, 6-month, 9-month, and 12-month were 61.53%, 42.30%, 23.07%, and 7.69%, respectively. Conclusion: Prolonged infusion of low dose gemcitabine is a tolerable and a good option in locally advanced or metastatic pancreatic carcinoma. There may be a benefit of that protocol in patients with bad performance status. More clinical trials with a combination of other cytotoxic agents or target therapy are needed to get better survival and lesser toxicity.

Cardiac Safety with High Cumulative Dose of Pegylated Liposomal Doxorubicin in Patients with Metastatic Breast Cancer Previously Treated with Conventional Anthracyclines

Introduction: The treatment of metastatic breast cancer (MBC) is still challenging. Many studies documented the efficacy of pegylated liposomal doxorubicin (PLD) in patients with MBC, but there is a limited data about the cardiac safety with high cumulative dose (HCD) of PLD. Aim of the work: We conducted this trial to outline the cardiac safety of HCD of PLD in patients with MBC who previously received conventional anthracyclines. Methods: During the period of nine years (January 2011 to December 2019). We extracted the data of the patients with MBC receiving PLD at Medical Oncology Department, South Egypt Cancer Institute, Assiut University. These included patients’ demographics and therapeutic data including the full data of PLD, prior conventional anthracyclines, prior trastuzumab, and prior radiotherapy. Also, data about comorbidities as well as cardiac and other toxicities of PLD were obtained. The data was analysed using SPSS v. 21. Results: For all 81 eligible patients, the mean age was 43.9 years (±standard deviation (SD) 13.2). The mean cumulative dose of PLD was 378.4 mg/m2 (± SD of 250.2) and a range of 100 - 1200 mg/m2. About thirty-one (38.3%) patients received high cumulative dose (400 mg/m2 or more), while the remaining 50 patients did not. The decline in left ventricular ejection fraction (LVEF) was relatively rare;and of low grade. Grade 2 decline in LVEF occurred in only two patients who received high cumulative dose of PLD, and only one patient who did not reach HCD (p = 0.555). Grade 3 or 4 decline in LVEF did not occur in patients either with or without HCD. Regarding other toxicities, there was a significant increase in incidence of all grades palmar plantar erythrodysesthesia (PPE) in patients who received HCD of PLD when compared to those who did not reach the HCD (38.7% versus 16% respectively;p = 0.021). Conclusion: Our study concluded that the use of PLD seems to be a justified agent in the treatment of MBC who previously treated by conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.

In Frail Elderly Patients, Low-Dose Gemcitabine over 6-Hour Infusion Is Equally Effective and Less Toxic Than the Standard Gemcitabine Protocol for Advanced Pancreatic Adenocarcinoma: A Randomized Phase II Trial

Background:?Treatment of frail elderly patients with pancreatic cancer is still a major problem due to intolerance to standard chemotherapy doses. Aim:?This study aims to compare the low-dose gemcitabine over 6 hours (LD6H) to the standard gemcitabine protocol in terms of clinical benefit, survival, and safety in the frail elderly patients with advanced pancreatic adenocarcinoma. Methods:?Patients enrolled in this trial were randomly assigned by in a 1:1 fashion via closed envelope method to either receive gemcitabine of 1000 mg/m2?over 30-minute infusion on days 1, 8, and 15 of every 4-week cycle (standard protocol arm) or gemcitabine as a weekly low-dose (250 mg/m2) over 6-hour infusion (LD6H arm). Results:?We enrolled eighty-two eligible frail elderly patients with advanced pancreatic cancer. The patients were randomly assigned to receive either standard gemcitabine protocol (40 patients) or low-dose (250 mg/m2) gemcitabine over 6-hour infusion, given weekly (42 patients). There was no significant difference between the standard group and low-dose group as regard of the overall response rate (p = 0.654), the disease control rate (DCR) (p = 0.845), the median progression-free survival (PFS) (p = 0.908) and the overall survival (OS) (p = 0.331). The low-dose regimen had a significantly lower incidence of adverse effects grades 3 or 4 when compared to the standard regimen: (p = 0.024 for fatigue, p = 0.027 for hypotension, p = 0.012 for each anemia as well as thrombocytopenia, and p = 0.006 for neutropenia). Conclusion:?Low-dose gemcitabine over 6-hour infusion is equally effective and less toxic when compared to standard gemcitabine protocol in frail elderly patients with advanced pancreatic adenocarcinoma. So, we recommend the low-dose gemcitabine for frail elderly patients with advanced pancreatic cancer.

Surrogate Role of CD85k on Monocytic Lineage Involved Leukemogenesis Biology and Clinical Aspect

Background: Unique receptor involved in leukemogenesis is CD85k;an immuneglobulin receptor for immune tolerance, CD36 is glycoprotein mediates cellular adhesion and metastatic spread, CD14, CD15 considered common monocytic markers. Aims: to investigate CD85k with monocytic lineage involved leukemia (MLIL) markers in leukemia pathogenesis and clinical presentation. Patients and Methods: 47 patients (32 diagnosed acute myeloid leukemia (AML);15 non-malignant hematological disease as a control), were included, aged from 2 to 80 years, all subjected to peripheral blood (P.Bl) and bone marrow (B.M) examination, immunophenotyping (IPT) using FASC Canto four color flow cytometer (FCM) Becton Dickenson (BD) USA, for CD13, CD33, MPO, HLA-DR, CD34, CD38, CD117, CD14, CD15 and CD36 the Mo Abs supplied by B.D Bioscience, and anti CD85k Mo Abs by Aveda de Coimbra Flamenco, reference No. 1399990130. Results: Frequency of CD85k is 19/32 (59.37%) of AML;14/14 (M4/M5) 100% positive CD85k, insignificant correlations of CD85k to sex, lymphadenopathy or organomegaly, platelets count and P.Bl blast (P > 0.05), significant to age 50,000 × 109/l, Hb 0.05). Conclusion: Although CD85k is MLIL associated marker, it is not correlated with other MLIL markers with frequency 100% in MLIL and 59.37% in AML, age predisposition is <35 years with no sex variation, significant correlation to progenitor and myeloid markers, it’s a crucial role in leukemogenesis biology, not in clinical presentations, considered good follow up predictor MLIL marker.