Hepatitis C-Associated Chronic Lymphoproliferative Disorders: A Single Center Experience

Hepatitis C virus (HCV) infection is a major public health concern in Egypt with its unique genotype. Besides liver disease, HCV is a lymphotropic virus involved in the pathogenesis of various extrahepatic diseases. A causative role of HCV in the generation of chronic lymphoproliferative diseases as well as its impact on disease behavior in HCV chronic carriers are not fully understood. We investigated the prevalence of HCV among cohort of Egyptian patients (n:84) with chronic lymphoproliferative diseases, the relation between HCV infection and the immunological state of this opulation and also their clinical and laboratory characteristics. High prevalence of HCV (40%) among Egyptian patients with chronic lymphoproliferative diseases with following subtype frequency was revealed; CLL (38.2%) followed by DLBCL (20.6%), and LPL (17.6%). We found significant correlation between HCV and platelet count (P=0.014), Albumin (P=0.02), LDH (P=0.014) and B2M (P=0.05). Otherwise, there were no significant correlations with other parameters especially the immunological assessment; serum immunoglobulins, Coombs test, and cryoglobulinemia. HCV prevalence among patients with chronic lymphoproliferative diseases is higher than that estimated in the general population. Those patients should be tested for HCV during the assessment. Our observations suggest that HCV may have an oncogenic role in Egyptian patients with chronic lymphoproliferative diseases and it may affect the prognostic markers in those populations

Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes. METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients. RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype. CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy

Helicobacter pylori associated to unexplained or refractory iron deficiency anemia: an Egyptian single-center experience

Background: Refractory or unexplained iron deficiency anemia accounts for about 15% of all cases. The endoscopic gastrointestinal workup sometimes fails to establish the cause of iron deficiency anemia and a considerable proportion of patients regardless of risk category fail to respond to oral iron supplementation. The aim of the present study was to assess the etiological role of Helicobacter pylori infection in adult Egyptian patients with unexplained or refractory iron deficiency anemia. Methods: A case controlled study was composed of 104 iron deficiency anemia cases and 70 age- and gender-matched healthy controls. Patients were diagnosed with iron deficiency anemia according to hemoglobin, mean corpuscular volume, serum ferritin, and transferrin saturation. Upper and lower endoscopies were performed and active H. pylori infection was investigated by testing for the H. pylori antigen in stool specimens. Hematological response to H. pylori treatment with triple therapy together with iron therapy (n = 32) or only iron therapy (n = 32) were assessed in patients with H. pylori infection. Results: H. pylori infection was more prevalent in patients with unexplained or refractory iron deficiency anemia (61.5%). Of the different hematological parameters investigated, there was a significant correlation only between H. pylori infection and mean corpuscular volume (p-value 0.046). Moreover, there was a significant correlation between receiving triple therapy together with iron supplementation and improvements in the hematological parameters [hemoglobin (p-value < 0.001), mean corpuscular volume (p-value < 0.001), iron (p-value < 0.001) and serum ferritin (p-value < 0.001)] compared to receiving iron supplementation alone. Conclusions: Failing to test for H. pylori infection could lead to a failure to identify a treatable cause of anemia and could lead to additional and potentially unnecessary investigations. Furthermore, treatment of H. pylori infection together with iron supplementation gives a more rapid and satisfactory response. Keywords: Helicobacter pylori, Iron deficiency anemia, Refractory iron deficiency, Unexplained iron deficiency, Microcytic anemi

Role of physical function in predicting short-term treatment outcome in Egyptian acute myeloid leukemia patients: a single center experience

Background: Acute myeloid leukemia (AML) is a potentially fatal hematological disease. Along with disease-related factors, patient-related factors, in particular age, are a strong predictor of outcome that influence treatment decisions. Many acute myeloid leukemia risk stratification models have been developed to predict the outcome of intensive chemotherapy. However, these models did not include physical function assessments. Methods: This study investigated the impact of several factors, namely the performance status, physical function and age on the short-term outcomes of intensive chemotherapy in a cohort of 50 Egyptian patients with de novo acute myeloid leukemia. Results: Complete remission after intensive chemotherapy in these myeloid leukemia patients at Day 28 was 56% and the mortality rate was 12% and 34% at Day 28 and Day 60, respectively. The pretreatment Eastern Cooperative Oncology Group score was significantly correlated with outcomes on Day 28 and Day 60 (p-value = 0.041 and p-value = 0.032, respectively). There were significant correlations between the two-minute walk test and outcomes of therapy on Day 28 and 60 (p-value = 0.032 and p-value = 0.047, respectively) and between grip strength test and outcomes of therapy on Day 28 and 60 (p-value = 0.046 and p-value = 0.047 respectively). Furthermore, there was a significant correlation between chair stand test and outcome of therapy on Day 28 (p-value = 0.023). Conclusion: Performance status and physical function assessments were strong predictors of outcome of intensive chemotherapy in acute myeloid leukemia and we recommend the incorporation of these variables in risk stratification models for the personalization of therapy before treating acute myeloid leukemia patients with intensive chemotherapy. Keywords: Acute myeloid leukemia, Physical functions, Performance status, ECO

Effectiveness of Adding a Salt Tolerant Crop to the Egyptian Crop Pattern to Adapt with the Water Salinity and Shortage Conditions

The imbalance between the high water demand and the limited water supplies in Egypt makes water resources management a big challenge. The Mediterranean Sea water intrusion is predicted to increase, causing high water salinity at the Nile delta. A future reduction in the Nile’s water supply is also expected to occur leading to further water stress. Such water shortage will increase the re-use of drainage water which leads to further increase in the water’s salinity. This study aims at adding a salt-tolerant crop to the traditional Egyptian crop pattern. Using quinoa is suggested as an alternative for wheat crop in areas with high water salinity, where the wheat’s productivity is negatively affected. The effectiveness of the proposed crop is evaluated by using the agriculture sector model for Egypt (ASME) which estimates the water demand and the agricultural productivity for different cropping patterns. The results show that quinoa is a good substitution that produces a reliable yield in the case of Nile flow reduction. A base case considering the current water supply conditions is first studied. Then, a 10% reduction in the Nile water supply and the population projection in the year 2030 are presented in two scenarios, one of which considers financial incentives for supporting quinoa. The results show that the Nile flow reduction adversely affects most of crops’ yields, and accordingly, decreases the total crops’ water productivity, but quinoa is found to have a potential high yield in case of water shortage. The total yield of both quinoa and wheat together decrease from 8,643 million tons to 8.223 million tons for the scenario of 10% Nile water reduction without economic incentives, while it jumps to 11.474 million tons&nbsp; under the same conditions but with &nbsp;incentives that encourage the farmers to cultivate quinoa

Role of Granulocyte-Macrophage Colony-Stimulating Factor in Acute Myeloid Leukemia/Myelodysplastic Syndromes

Purpose: Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine stimulates growth, differentiation, and function of myeloid progenitors. We aimed to study the role of GM-CSF gene expression, its protein, and antibodies in patients with acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) and their correlation to disease behavior and treatment outcome. The study included 50 Egyptian patients with AML/MDS in addition to 20 healthy volunteers as control subjects. Patients and Methods: Assessment of GM-CSF gene expression was performed by quantitative real-time polymerase chain reaction. GM-CSF proteins and antibodies were assessed by enzyme-linked immunosorbent assay. Results: There was significant decrease in GM-CSF gene expression (P = .008), increase in serum level of GM-CSF protein (P = .0001), and increase in anti–GM-CSF antibodies (P = .001) in patients with AML/MDS compared with healthy control subjects. In addition, there was a significant negative correlation between serum levels of GM-CSF protein and initial peripheral blood blasts, percentage as well as response to therapy. Conclusion: Any alteration in GM-CSF gene expression could have implications in leukemogenesis. In addition, GM-CSF protein serum levels could be used to predict outcome of therapy. GM-CSF antibodies may also play a role in the pathogenesis of AML/MDS. The use of these GM-CSF parameters for disease monitoring and as markers of disease activity needs further research

The Outcomes and Adverse Drug Patterns of Immunomodulators and Thrombopoietin Receptor Agonists in Primary Immune Thrombocytopenia Egyptian Patients with Hemorrhage Comorbidity

Immune thrombocytopenia (ITP) treatment has evolved recently. However, none of the treatments have only benefits without drawbacks. This study aimed to compare the clinical outcomes and adverse drug patterns of Eltrombopag, Romiplostim, Prednisolone + Azathioprine, High Dose-dexamethasone (HD-DXM) (control group), and Rituximab in primary ITP Egyptian patients. All patients were initiated with corticosteroids, HD-DXM, as a first-line treatment for the first month immediately following diagnosis. Four hundred sixty-seven ITP patients were randomly assigned to five groups. The outcome measures were judged at baseline, at the end of treatment (6 months), and after an additional 6-month free treatment period. The follow-up period for which relapse is noted was 6 months after the end of treatment. Eltrombopag and Romiplostim resulted in a significantly higher incidence of sustained response than Rituximab, HD-DXM, and Prednisolone + Azathioprine (55.2% and 50.6% vs. 29.2%, 29.1%, and 18%, respectively; p-value p-value < 0.01). We also describe 23 reports of pulmonary hypertension with Prednisolone+ Azathioprine and 13 reports with HD-DXM. The thrombotic events occurred in 16.6% and 13% of patients who received Eltrombopag and Romiplostim treatment, respectively. Most patients had at least one or two risk factors (92.8% of cases). Corticosteroids are effective first-line therapy in primary ITP patients. However, relapse is frequent. Eltrombopag and Romiplostim are safer and more effective than Prednisolone, HD-DXM, and Rituximab. They might be reasonable beneficial options after a one-month HD-DXM regimen

Therapeutic Outcomes of High Dose-Dexamethasone versus Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim Strategies in Persistent, Chronic, Refractory, and Relapsed Immune Thrombocytopenia Patients

Background: Primary immune thrombocytopenia (ITP) is an inflammatory autoimmune disease that can be managed with several treatment options. However, there is a lack of comparative data on the efficacy of these options in different phases of the disease. Aim of the study: This study aimed to evaluate the efficacy of high-dose Dexamethasone (HD-DXM), Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim schedules in persistent, chronic refractory or relapsed Egyptian ITP patients with a platelet count ≤30 × 109/L. The primary outcome measure was a sustained increase in platelet counts over 50 × 109/L for an additional 12 months without additional ITP regimens. The study also aimed to identify a suitable treatment regimen with a long remission duration for each phase of ITP. Results: Prednisolone + Azathioprine was significantly more effective in achieving an overall response in persistent patients than Romiplostim, high-dose Dexamethasone, and Rituximab. (90.9% vs. 66.6, [Odds ratio, OR: 5; confidence interval, CI 95% (0.866–28.86)], 45%, [OR: 0.082, CI 95% (0.015–0.448)] and, 25%, [OR: 30, CI 95% (4.24–211.8)], respectively, p-value p-value < 0.01). Conclusions: Finally, Eltrombopag following HD-DXM showed the highest percentage of patients with complete treatment-free survival times of at least 330 days. These findings could help clinicians choose the most appropriate treatment for their patients with ITP based on the phase of the disease. This trial is registered in clinicaltrials.gov with registration number NCT05861297