Favorable outcome of non-myeloablative allogeneic transplantation in adult patients with severe sickle cell disease: A single center experience of 200 patients.

Allogeneic hematopoietic stem cell transplant (HSCT) for adults with severe sickle cell disease (SCD) is potentially curative but not commonly utilized therapy due to complications such as graft failure (GF) and organ toxicity. Herein, we are reporting our long-term outcome data of non-myeloablative (NMA) HSCT in adults with severe SCD with emphasis on factors predicting event free survival (EFS). Adults with severe SCD undergoing NMA match-related donor allogeneic HSCT from 2015 to 2021 with at least 12 months of follow-up were included. A total of 200 patients were included with a median age of 26 years (14-43) and 56% were male. The median infused CD34 dose was 13.7 (5.07-25.8), respectively. Median absolute neutrophil count engraftment was 19 (13-39) days with 51% of patients receiving GCSF to expedite recovery. A total of 17 patients experienced GF; 3 as primary and 14 as secondary within a median time of 204 days (40-905). A 76% successfully discontinued sirolimus at the last follow-up. Median follow-up for the cohort is 29.2 (2.1-71.4) months. Estimated 3-year EFS and OS were 88.2% (81.9-92.5) and 94.6% (89.2-97.3). At multivariable analysis, minor ABC incompatibility hazard ratio (HR) 4 (1.3-12.1; 0.014) and allo-antibody against non-ABO donor antigens HR 4.3 (1.3-14.1; 0.016) were significant for EFS. No clonal evolution or myeloid malignancies were seen. This largest single-center report of NMA HSCT in adults with severe SCD further delineated its feasibility, potential toxicities, and fertility outcomes. GF remains a major impediment and appears dependent on ABO matching and non-ABO antibodies.

MICaFVi: A Novel Magnetic Immuno-Capture Flow Virometry Nano-Based Diagnostic Tool for Detection of Coronaviruses.

COVID-19 has resulted in a pandemic that aggravated the world's healthcare systems, economies, and education, and caused millions of global deaths. Until now, there has been no specific, reliable, and effective treatment to combat the virus and its variants. The current standard tedious PCR-based tests have limitations in terms of sensitivity, specificity, turnaround time, and false negative results. Thus, an alternative, rapid, accurate, and sensitive diagnostic tool that can detect viral particles, without the need for amplification or viral replication, is central to infectious disease surveillance. Here, we report MICaFVi (Magnetic Immuno-Capture Flow Virometry), a novel precise nano-biosensor diagnostic assay for coronavirus detection which combines the MNP-based immuno-capture of viruses for enrichment followed by flow-virometry analysis, enabling the sensitive detection of viral particles and pseudoviruses. As proof of concept, virus-mimicking spike-protein-coated silica particles (VM-SPs) were captured using anti-spike-antibody-conjugated MNPs (AS-MNPs) followed by detection using flow cytometry. Our results showed that MICaFVi can successfully detect viral MERS-CoV/SARS-CoV-2-mimicking particles as well as MERS-CoV pseudoviral particles (MERSpp) with high specificity and sensitivity, where a limit of detection (LOD) of 3.9 µg/mL (20 pmol/mL) was achieved. The proposed method has great potential for designing practical, specific, and point-of-care testing for rapid and sensitive diagnoses of coronavirus and other infectious diseases.

Comparison of a modified pediatric protocol versus a hyper-CVAD protocol in adolescents and young adults with Philadelphia-negative acute lymphoblastic leukemia: A multicenter retrospective analysis.

BACKGROUND: The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. MATERIALS AND METHODS: In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. RESULTS: A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. CONCLUSION: Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.

Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a refined classification from the European society for blood and marrow transplantation (EBMT).

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). A new definition for diagnosis, and a severity grading system for SOS/VOD in adult patients, was reported a few years ago on behalf of the European Society for Blood and Marrow Transplantation (EBMT). The aim of this work is to update knowledge regarding diagnosis and severity assessment of SOS/VOD in adult patients, and also its pathophysiology and treatment. In particular, we now propose to refine the previous classification and distinguish probable, clinical and proven SOS/VOD at diagnosis. We also provide an accurate definition of multiorgan dysfunction (MOD) for SOS/VOD severity grading based on Sequential Organ Failure Assessment (SOFA) score.

Hematological indices in the adult saudi population: Reference intervals by gender, age, and region.

Introduction: Hematological parameters are critical in disease diagnosis, management, and monitoring; however, complete blood count (CBC) reference intervals vary across populations. The aim of the current study was to provide the reference ranges of hematological parameters/indices in the healthy adult Saudi population. Methods: A multicenter retrospective cross-sectional study was conducted with a sample of employees who were screened pre-employment from January 2015 to December 2019, at tertiary care hospitals in three regions. Demographic and CBC data were extracted from the electronic health system. The 2.5th and 97.5th percentiles were used to determine the reference intervals. Results: Of a total of 1,388 participants, 53.82% were male. The majority 96% was less than 40 years old, and 85% were from the Central region. Gender-related differences were observed for the RBC count, Hb, HCT, MCV, MCH, MCHC, and the platelet count. Age-related differences were observed for the RBC, Hb, HCT, and eosinophils. The WBC parameters did not differ by gender or age categories. Region-related differences were observed for the RBC, hemoglobin, HCT, MCV, WBC, and basophils. The platelet count was higher in the female group, the age group 40 years and above, and in the Western region. The prevalence of anemia was high in the female group and the Eastern region. The overall neutropenia rate was 12.8%. Conclusion: The data from this study provide hematological parameter reference ranges for the adult Saudi population by gender, age, and region. Gender and age-related differences were observed for the hematological parameters. Anemia was more frequent in the female group and the Eastern region. Caution must be taken when comparing or interpreting results from different age groups, gender, region of origin, and ethnicity.

Radiological outcome of bone disease in multiple myeloma patients pre- and post therapy: A single center experience.

OBJECTIVES: To find any correlation between the clinical response as per International Working Myeloma Group (IWMG) response criteria and the radiological response at the end of treatment. METHODS: A retrospective cohort study was conducted, total of 39 patients whom diagnosed with multiple myeloma (MM) between January 2010 and December 2018 and fulfilled the study criteria were included. RESULTS: The high sensitivity and specificity of positron emission tomography/computed tomography (PET/CT) in detecting osteolytic myeloma lesions in the bones was strongly emphasized in our study. Follow up PET/CT, we found that while 17 patients showed complete remission in PET/CT, and 14 of these of patients demonstrated a complete clinical response at end of therapy assessment. CONCLUSION: Although we did not find a statistically significant correlation between the response versus metabolic activity and the number of bone/bone marrow lesions, however, our study was limited by the absence of clear criteria for defining disease response in PET/CT in MM patients. Further prospective analysis would be needed to establish a defined criterion.

Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial.

OBJECTIVE: To evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo. METHODS: In this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality. RESULTS: Two hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32-44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6-12 days) in the favipiravir group and 8 days (IQR: 6-12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571-1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4-11 days) in the favipiravir group and 7 days (IQR: 5-10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events. CONCLUSION: In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.

Promising remissions in relapsed refractory classical Hodgkin lymphoma patients requiring multiple salvage regimens before transplantation in the brentuximab vedotin era.

Relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients refractory to first line salvage have poor outcomes. Herein we report the outcome of R/R cHL patients requiring ≥two vs. one line in the era of chemo-immunotherapy. Among 55 R/R cHL patients, 33 (60%) required one, 22 (40%) required ≥two lines. At 2 years, the estimated PFS and OS for patients requiring one vs. ≥two lines was 71.2% (50.1-84.7) vs. 51.9% (27.6-71.6), p= 0.16 and 84.6% (63-94) vs. 84% (58-95), p= 0.88, respectively. Patients requiring ≥two salvage lines prior to HCT can achieve comparable outcomes to those requiring one, possibly due to brentuximab vedotin leading to higher CMR rates.

Screening Practices, Knowledge and Adherence Among Health Care Professionals at a Tertiary Care Hospital.

INTRODUCTION: Screening, a routine procedure done on individuals with or without disease, results in the early detection of disease. The aim of this study was to assess healthcare professionals' (HCPs) level of knowledge related to and the adherence to screening. METHODS: A survey was conducted in HCPs, using a self-administered questionnaire. Knowledge was defined based on the correct or incorrect responses to the questions. Adherence to screening was considered if a test was done at least once in the past one year. RESULTS: Of the 379 participants, 61% were nurses, 34% physicians, and 5% pharmacists. The majority 68.78% were female. The average age of pharmacists was 29.17±7.09, physicians 35.57±10.08, and nurses 35.46±8.63 years. The knowledge related to breast cancer screening ranged between 50% and 57% and of a Pap smear, 41-54%. 94% nurses and 90% pharmacists had recorded an incorrect response to the required age of colon cancer screening. The overall screening adherence to diabetes was 46%, hypertension 68%, liver profile 43%, lipid profile 50%, breast cancer 10.38%, Pap smear 26%, prostate cancer 33%, and colon cancer 2.37%. HCPs aged ≥45 years had good adherence to diabetes screening. Pharmacists (88%) had the highest level of adherence to hypertension screening. Female HCPs poorly adhered to breast 38% and cervical cancer 26% screening. Only a third 33% of males, aged > 50 years, were screened for prostate cancer. Among HCPs aged ≥50 years (n=32), only three were screened for colon cancer. CONCLUSION: Despite the increased incidence of diabetes, breast and colon cancer in Saudi Arabia, HCPs displayed poor knowledge related to screening. The adherence to diabetes screening was good. However, HCPs in a high-risk group displayed poor adherence to screening, specifically for breast, cervical and colon cancer. The medical and cancer screening guidelines should be made available to all HCPs regardless of their specialty.

Management Approach to Acute Myeloid Leukemia Leveraging the Available Resources in View of the Latest Evidence: Consensus of the Saudi Society of Blood and Marrow Transplantation.

PURPOSE: Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults and is responsible for the majority of cancer-related mortality. In Saudi Arabia, leukemia is ranked the fifth most prevalent type of malignancy in adults. Our aim is to review existing epidemiologic data in Saudi Arabia and develop consensus guidelines for management of AML. METHODS: We review literature related to AML epidemiology, treatment patterns, and outcomes in Saudi Arabia, as well as literature related to the current advances in AML treatment. A panel of 10 experts from eight institutions in Saudi Arabia reviewed the literature and developed a consensus statement. RESULT: We provide an update of the available AML epidemiologic data in Saudi Arabia and describe recent developments in the diagnostic workup, risk stratification, and treatment algorithm. The consensus recommendations for the management of AML in Saudi Arabia were developed. CONCLUSION: The recommendations are in parallel with the recent international guidelines for the diagnosis and management of AML.

In vitro assessment of the efficiency of the PIM-1 kinase pharmacological inhibitor as a potential treatment for Burkitt's lymphoma.

Burkitt's lymphoma is an aggressive form of lymphoma affecting B lymphocytes. It occurs endemically in Africa and sporadically in the rest of the world. Due to the high proliferation rate of this tumor, intensive multi-drug treatment is required; however, the risk of tumor syndrome lysis is high. Overexpression of the proto-oncogene proviral integration of the Moloney murine leukemia virus (PIM-1) kinase is associated with the development of hematological abnormalities, including Burkitt's lymphoma (BL). PIM-1 primarily exerts anti-apoptotic activities through BAD phosphorylation. The aim of the present study was to investigate the in vitro efficiency of a PIM-1 kinase pharmacological inhibitor (PIM1-1) in BL. The impact of PIM1-1 was evaluated in terms of the viability and apoptosis status of the BL B cell lines, Raji and Daudi, compared with K562 leukemia cells, which highly express PIM-1. Cell viability and apoptotic status were assessed with western blotting, and PIM-1 gene expression was assessed with reverse transcription-quantitative PCR. After 48 h of treatment, PIM1-1 inhibited the Daudi, Raji and K562 cell viability with a half-maximal inhibitory concentration corresponding to 10, 20 and 30 µM PIM1-1, respectively. A significant decrease of ERK phosphorylation was detected in PIM1-1-treated Daudi cells, confirming the antiproliferative effect. The addition of 10 µM PIM1-1 significantly decreased the PIM-1 protein and gene expression in Daudi cells. An inhibition of the pro-apoptotic BAD phosphorylation was observed in the Daudi cells treated with 0.1-1 µM PIM1-1 and 10 µM PIM1-1 decreased BAD phosphorylation in the Raji cells. The apoptotic status of both PIM1-1-treated cells lines were confirmed with the detection of cleaved capase-3. However, no change in cell viability and PIM-1 protein expression was observed in the 10 µM PIM1-1-treated K562 cells. In conclusion, the findings indicated that the PIM1-1 pharmacological inhibitor may have therapeutic potential in BL, but with lower efficiency in leukemia.

A Drug Repositioning Approach Identifies a Combination of Compounds as a Potential Regimen for Chronic Lymphocytic Leukemia Treatment.

Drug repositioning is a promising and powerful innovative strategy in the field of drug discovery. In this study, we screened a compound-library containing 800 Food and Drug Administration approved drugs for their anti-leukemic effect. All screening activities made use of human peripheral blood mononuclear cells (PBMCs), isolated from healthy or leukemic donors. Compounds with confirmed cytotoxicity were selected and classified in three groups: i) anti-neoplastic compounds which are drugs used in leukemia treatment, ii) compounds known to have an anti-cancer effect and iii) compounds demonstrating an anti-leukemic potential for the first time. The latter group was the most interesting from a drug repositioning perspective and yielded a single compound, namely Isoprenaline which is a non-selective ß-adrenergic agonist. Analysis of the cytotoxic effect of this drug indicated that it induces sustainable intracellular ATP depletion leading, over time, to necrotic cell death. We exploited the Isoprenaline-induced intracellular ATP depletion to sensitize primary leukemic cells to fludarabine (purine analogue) and Ibrutinib (Bruton's tyrosine kinase inhibitor) treatment. In-vitro treatment of primary leukemic cells with a combination of Isoprenaline/fludarabine or Isoprenaline/Ibrutinib showed a very high synergistic effect. These combinations could constitute a new efficient regimen for CLL treatment following successful evaluation in animal models and clinical trials.

Impact of cluster of differentiation 20 expression and rituximab therapy in classical Hodgkin lymphoma: Real world experience.

The prognostic impact of CD20 expression and rituximab therapy in classical Hodgkin lymphoma (cHL) is unclear. Among 310 patients, CD20 was expressed in 66 (22%) cases. The 3-year PFS was 75.1% for CD20+and 70% for CD20- (p = 0.36). The 3-year PFS was 84.7% for the rituximab group and 67.8% for the no rituximab group (p = 0.23). Only constitutional symptoms and positive interim PET/CT were significantly associated with worse outcome, HR 3.2 (1.14-9.01; p = 0.028) and 4.3 (2.27-8.1; p < 0.0001), respectively. Neither CD20 expression nor rituximab use significantly impacted outcome.