Effect of AGM and Fetal Liver-Derived Stromal Cell Lines on Globin Expression in Adult Baboon (P. anubis) Bone Marrow-Derived Erythroid Progenitors

This study was performed to investigate the hypothesis that the erythroid micro-environment plays a role in regulation of globin gene expression during adult erythroid differentiation. Adult baboon bone marrow and human cord blood CD34+ progenitors were grown in methylcellulose, liquid media, and in co-culture with stromal cell lines derived from different developmental stages in identical media supporting erythroid differentiation to examine the effect of the micro-environment on globin gene expression. Adult progenitors express high levels of γ-globin in liquid and methylcellulose media but low, physiological levels in stromal cell co-cultures. In contrast, γ-globin expression remained high in cord blood progenitors in stromal cell line co-cultures. Differences in γ-globin gene expression between adult progenitors in stromal cell line co-cultures and liquid media required cell-cell contact and were associated with differences in rate of differentiation and γ-globin promoter DNA methylation. We conclude that γ-globin expression in adult-derived erythroid cells can be influenced by the micro-environment, suggesting new potential targets for HbF induction

Prevalence of Microalbuminuria in Adult Patients with Sickle Cell Disease in Eastern Saudi Arabia

Background. Proteinuria is a common feature of sickle cell nephropathy (SCN) that can progress to renal insufficiency and end stage renal disease. Microalbuminuria (MA) is the earliest manifestation of SCN and precedes the development of overt proteinuria. In addition to the renal consequences, MA is linked to cardiovascular complications. Periodic screening and early detection of MA allow early intervention that may reduce the risk of progression to advanced renal failure and cardiovascular diseases. Objective. The aim of this study was to investigate the prevalence of MA in patients with SCD in the eastern region of Saudi Arabia. Methods. A prospective cross-sectional observational study was conducted at Johns Hopkins Aramco Healthcare (JHAH). Urine samples of SCD patients 18 years old and older were tested for the presence of MA using urinary albumin over creatinine ratio (ACR). Correlation was tested with multiple variables including age, gender, body mass index (BMI), hemoglobin level, blood pressure, blood transfusion history, pain episodes, and use of hydroxyurea. Results. Urine samples were tested on 72 patients. The mean age of the study cohort was 35±16.9 years. Microalbuminuria was detected in 18 patients (25%). No correlation was found with any of the tested variables. Conclusion. Microalbuminuria is a common finding in patients with SCD in eastern Saudi Arabia. Patients with SCD should be screened for MA, and those with positive tests should probably be treated with antiproteinuric agents that may slow the progression to advanced stages of renal failure and decrease the risk of cardiovascular diseases

End-stage renal disease in patients with sickle cell disease

Sickle cell nephropathy is a severe complication of sickle cell disease (SCD) that has a wide range of manifestations, from asymptomatic microalbuminuria to end-stage renal disease (ESRD). The data on patients with SCD who develop ESRD are scarce. The aim of this study was to explore the course of patients with SCD who developed ESRD and received renal replacement therapy (RRT). The course of patients with SCD who developed ESRD and started dialysis at two centers in the Eastern Province of Saudi Arabia was retrospectively analyzed. Parameters included age at initiation of dialysis, survival until death or kidney transplantation, hospitalization due to pain crisis, disease-related parameters, and requirement for blood transfusion. Sixteen patients with SCD developed ESRD and started RRT with either hemodialysis or peritoneal dialysis. The mean age at initiation of dialysis was 46.6 years. The majority of patients (10 out of 16) were resistant to erythropoiesis-stimulating agents (ESA) and required blood transfusion repeatedly. Pain crises were infrequently encountered. Median survival was 54 months. Four patients received kidney transplantation with good outcome. In conclusion, most patients with SCD who developed ESRD were resistant to ESA and required repeated blood transfusion. The rate of hospitalization due to pain crisis was relatively low. Survival on dialysis was comparable to that of patients with no SCD, and the post-transplant course was relatively benign

Minimal residual disease program for acute lymphoblastic leukemia at Dhahran Health Center

Background and Objectives: Minimal residual disease (MRD) assays for monitoring acute lymphoblastic leukemia (ALL) during treatment are defined as assays with a limit of detection of at least 0.01% leukemic blasts per mononuclear cells or total nucleated cells. Settings and Design: We retrospectively reviewed out experience at Dhahran Health Center in monitoring adult and pediatric ALL patients with a MRD assay based on immunophenotyping by flow cytometry with a level of detection of 0.01% leukemic blasts per mononuclear cells and compute Kaplan–Meier survival analysis for overall survival (OS) and relapse-free survival (RFS). We also demonstrated the incorporation of an estimated measurement uncertainty for the reported MRD values based on metrological principles. Methods: A retrospective review of all cases diagnosed with ALL from 2006 to 2012 was undertaken and after applying exclusion criteria, 26 cases were identified and patient chart review was done. Results: Although the Kaplan–Meier survival analysis for OS and RFS do demonstrate a statistically significant difference between MRD positive and negative patients, none of the pediatric ALL MRD positive cases have relapsed till now. Conclusions: The detection of MRD in ALL opens up the opportunity to intensify or alter treatment for patients with detectable levels by a highly sensitive assay before clinical relapse