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.

Improved Quality of Life of Patients With Sickle Cell Disease after Allogeneic Stem Cell Transplant: Another Indication for Transplant.

BACKGROUND: Sickle cell disease (SCD) is frequently inherited worldwide. The severity of SCD ranges from mild to severe, and the disease involves multiple complications, including pulmonary hypertension, stroke, recurrent vaso-occlusive crises, end-organ damage, and an increased mortality risk. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option for patients with SCD. OBJECTIVES OF THE STUDY: The objective was to assess the quality of life of adolescent and adult patients with SCD receiving HCT pre-and post-transplant. METHODS: An analytical cross-sectional study was conducted. Patients with SCD with at least one year of follow-up after HCT were interviewed to assess their quality of life pre-and post-transplant. This study was conducted at the Transplant Center of King Abdulaziz Medical City, Riyadh. The participants were identified through non-probability consecutive sampling. The FACT-G questionnaire was used to assess the quality of life domains. RESULTS: Thirty-one patients were included. The median age of the respondents was 32 ± 6.3 years, and 16 were male (51.6%). The most frequent indication for stem cell transplantation (58%) was a vaso-occlusive crisis. The mean FACT-G scores pre- and post-transplantation were 55.2 ± 18.17 and 91 ± 14.58, respectively. The mean number of annual ER visits was significantly reduced from 27.3 pre-transplant to 6.6 post-transplant (P-value = 0.006). Of the respondents, 51.6% experienced no severe complications post-transplantation, and most (93.5%) reported improved quality of life. CONCLUSION: HCT significantly improved the quality of life of adult patients with SCD, with improvements in most FACT-G score domains. Although it was not measured by the FACT-G, the frequency of ER visits and hospital admissions were reduced significantly post-transplant, reflecting an improvement in the quality of life and a reduction in the cost of therapy for patients with SCD.

Comparing Invasive Pulmonary Aspergillosis Mortality Between Liposomal Amphotericin B and Voriconazole in Patients With Hematological Malignancy or Hematopoietic Stem Cell Transplantation.

Objectives We evaluated liposomal amphotericin B versus voriconazole for the treatment of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT). Methods This retrospective cohort, single-center study included patients with compatible radiological diagnosis of IPA between 2016 and 2021. Results Forty-six patients with hematological malignancy or HSCT were diagnosed with IPA. Thirty-nine of them fulfilled the criteria for comparing liposomal amphotericin B (n=15) with voriconazole (n=24). Their median age was 48.5 years. Stem cell transplant recipients were 45.65%, and nearly half of the patients (47.83%) had acute myeloid leukemia. Twenty-six (56.52%) of the patients did not require oxygen therapy. The 12-week mortality was 13.33% (two out of 15) in patients who received liposomal amphotericin B compared to 25% (six out of 24) in patients who received voriconazole. There was no mortality judged to be related to IPA. Success or global clinical response was not different between the two drugs: 80% for liposomal amphotericin B versus 83.33% for voriconazole. However, the safety profile favored liposomal amphotericin B. Conclusion In this small cohort, there was an equipoise in the mortality and clinical and radiological outcomes obtained using liposomal amphotericin B or voriconazole for the treatment of IPA in hematological malignancy or HSCT.

Molecular Docking as a Potential Approach in Repurposing Drugs Against COVID-19: a Systematic Review and Novel Pharmacophore Models.

Purpose of Review: This article provides a review of the recent literature related to the FDA-approved drugs that had been repurposed as potential drug candidates against COVID-19. Moreover, we performed a quality pharmacophore study for frequently studied targets, namely, the main protease, RNA-dependent RNA polymerase, and spike protein. Recent Findings: Ever since the COVID-19 pandemic, the whole spectrum of scientific community is still unable to invent an absolute therapeutic agent for COVID-19. Considering such a fact, drug repurposing strategies seem a truly viable approach to develop novel therapeutic interventions. Summery: Drug repurposing explores previously approved drugs of known safety and pharmacokinetics profile for possible new effects, reducing the cost, time, and predicting prospective side effects and drug interactions. COVID-19 virulent machinery appeared similar to other viruses, making antiviral agents widely repurposed in pursuit for curative candidates. Our main protease pharmacophoric study revealed multiple features and could be a probable starting point for upcoming research.

Clinical Characteristics and Risk Factors Associated with Severe Disease Progression among COVID-19 Patients In Wad Medani Isolation Centers: A Multicenter Retrospective Cross-Sectional Study.

Background: Since December 2019, (COVID-19) has had a significant impact on global health systems. Because little is known about the clinical characteristics and risk factors connected with COVID-19 severity in Sudanese patients, it is vital to summarize the clinical characteristics of COVID-19 patients and to investigate the risk factors linked to COVID-19 severity. Objectives: We aimed to assess the clinical characteristics of COVID-19 patients and look into risk factors associated with COVID-19 severity. Methods: This is a retrospective cross-sectional study that took place in two Isolation Centers in Wad Medani, Gezira State, Sudan. Four hundred and eighteen patients were included between May 2020 and May 2021. All COVID-19 patients over the age of 18 who were proven COVID-19 positive by nucleic acid testing or had characteristics suggestive of COVID-19 on a chest CT scan and had a complete medical record in the study period were included. Results: The participants in this study were 418 confirmed COVID-19 cases with a median age of 66.313 years. There were 279 men (66.7%) among the patients. The most prevalent comorbidities were hypertension (n = 195; 46.7%) and diabetes (n = 187; 44.7%). Fever (n = 303; 72.5%), cough (n = 278; 66.5%), and dyspnea (n = 256; 61.2%) were the most prevalent symptoms at the onset of COVID-19. The overall mortality rate (n = 148) was 35.4%. Patients with severe illness had a mortality rate of 42.3% (n = 118). Older age, anemia, neutrophilia, and lymphocytopenia, as well as higher glucose, HbA1c, and creatinine levels, were all linked to severe COVID-19, according to the chi-square test and analysis of variance analysis. Conclusion: Sixteen variables were found to be associated with COVID-19 severity. These patients are more prone to go through a serious infection and as a result have a greater death rate than those who do not have these characteristics.

Severe first infusion reaction related to cetuximab in cancer patients in Arkansas.

INTRODUCTION: Cetuximab, a chimeric monoclonal antibody, is a commonly used anticancer drug that prevents binding of epidermal growth factor to epidermal growth factor receptor. It has been widely used in a variety of cancers since its initial approval by the FDA in 2004. Despite its efficacy, it has met with some genuine concerns especially regarding the anaphylactoid reactions occurring after first infusions. Cetuximab-related first infusion reaction has been found to be much more prevalent in the Southeastern United States with several studies from the southern United States supporting it. The purpose of our study was to determine the rate of first infusion reaction in the state of Arkansas and the factors that could predispose to first infusion reaction. METHODS AND RESULTS: We performed a retrospective chart review of consecutive patients who received cetuximab between January 2004 and December 2016 at the University of Arkansas for Medical Sciences. We included a total of 220 patients in our analysis out of which 32 (14.5%) developed cetuximab-related first infusion reaction. There was a statistically significant increased risk in males versus females (18.2% vs. 8.4%, P = 0.045) and trend toward significance for the difference between Caucasians and Blacks (16.5% vs. 7.1%, P = 0.054). CONCLUSION: There is increased incidence of cetuximab-related first infusion reaction in Arkansas which is much higher than the national average but comparable to the incidence in other neighboring states in the Southeastern United States. This increased incidence tends to cluster in Caucasian males. Safer alternatives should be preferred for treatment of cancers particularly in the Southeastern United States whenever possible.