Thrombotic Microangiopathy Post-COVID-19 Vaccination.

The emergence of COVID-19 has caused a wide spectrum of symptoms, ranging from asymptomatic to devastating symptoms, leading to death. One of the most serious complications of COVID-19 is the thromboembolic phenomenon, which has led to increased morbidity and mortality. Several vaccines were developed to protect against this infection and used widely across the globe. However, thromboembolic events were observed in the vaccinated population and were certainly the most commonly reported events following the COVID-19 vaccination. Although the thrombotic complications of COVID-19 were poorly understood, hyper-inflammatory responses were thought to be one of the main explanations for this infection sequel. In the setting of COVID-19 vaccines, there is still no clear understanding of the thrombosis pathophysiology, and, again, exaggerated pro-inflammatory and immune-mediated processes seem to be leading causes. Definitely, with the rise in reported cases of serious complications and increased awareness of these phenomena, we learn new theories and explanations that help us understand and manage those patients. We report the case report of two patients we managed over the last three years who presented with thrombotic microangiopathy following the COVID-19 vaccination.

Gene Mutations Associated With Chronic Lymphocytic Leukemia (CLL) Among Saudi CLL Patients and Treatment Outcomes: A Single-Center Experience.

Background Chronic lymphocytic leukemia (CLL) starts in white blood cells in the peripheral blood (stages 0 and 1). In CLL, leukemia cells often build up slowly. Many gene mutations are associated with CLL, such as trisomy 12, 13q14 deletion, and 17q deletion. Due to the lack of patients' disease characteristics, gene mutations, and treatment outcomes data among Saudi patients, this study aimed to identify the relation between the gene mutations of CLL and the treatment in King Abdulaziz Medical City (KAMC), Riyadh. Methods This cross-sectional study used data from the BESTCare hospital information system. The study included all patients diagnosed with CLL and confirmed by flow cytometry in KAMC, Riyadh, between January 2010 and October 2020. The data included demographic information, mutation type or chromosome, present comorbidity, and type of treatment. Results The study included 100 CLL patients. According to different types of clusters of differentiation (CD), CD5 was positive in 84 (84%) patients, and 88 (88%) patients were positive for CD19. Cytogenetic remarkers were tested, revealing that 21 (21%) patients with trisomy 12 and 20 (20%) were positive for 13q14 deletion. Observation of patients' disease status based on the cytogenetic remarkers showed that out of 15 patients with trisomy, 12 (80%) had not progressed and were stable and alive. Out of 20 patients with 13q14 deletion, 16 (80%) were alive and 13 (65%) patients were stable. Conclusion CLL patients in KAMC, Riyadh, displayed trisomy 12, which is characterized by the worst prognosis of disease status, as the most frequently detected cytogenetic aberration followed by 13q deletion. However, most patients were stable and alive.

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.

Outcome of Middle East Respiratory Syndrome (MERS) in hematology and oncology patients: A case series in Saudi Arabia.

BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is associated with a high fatality rate (34%), which is higher in the presence of co-morbidities. The aim of the current study was to assess the clinical course and the outcome in hematological or oncological malignancy cases, diagnosed with MERS-CoV. METHODS: This is a case series of hematological /oncological cases, diagnosed with MERS-CoV, in a tertiary care setting in 2015. The cases were identified based on the World Health Organization (WHO) MERS-CoV case definition. The demographic, clinical, and outcome data were retrieved from the patients' medical charts and electronic health records. RESULTS: In total, nine hematological or oncological cases were identified, diagnosed with MERS-CoV. The baseline malignant condition was hematological malignancy in seven patients, as well as colon cancer and osteosarcoma in one patient each. Six (67%) patients were male. The median age was 65 years (range 16-80 years). Co-morbidities included chronic kidney disease (n = 3.33%), diabetes mellitus (n = 3.33%), and hypertension (n = 2.22%). The presenting symptoms were shortness of breath (n = 6.66%), fever (n = 5.55%), cough (n = 2.22%), and diarrhea (n = 2.22%). Chest x-rays indicated bilateral infiltrates in 6 patients (66%). The PCR (polymerase chain reaction) test was repeated in six patients to confirm the diagnosis. The mortality rate was 100%, and the median time to death was 26 days (range 15-77 days). CONCLUSION: MERS-CoV infection in this small cohort of hematology or oncology patients has a 100% mortality rate, regardless of the status of the underlying disease. The confirmation of the diagnosis may require repeated testing. Additional studies are required to verify the findings and to elucidate the disease pathogenesis in cancer patients.

Highlights of the Management of Adult Histiocytic Disorders: Langerhans Cell Histiocytosis, Erdheim-Chester Disease, Rosai-Dorfman Disease, and Hemophagocytic Lymphohistiocytosis.

Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges in their diagnosis and management. With the discovery of novel molecular targets and the incorporation of targeted agents in the management of various adult histiocytic disorders, their management has become increasingly complex. In an attempt to improve the understanding of the clinical features and management of common adult histiocytic disorders (Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis), we created this document based on existing literature and expert opinion.

Reactivation of tuberculosis following ruxolitinib therapy for primary myelofibrosis: Case series and literature review.

Primary myelofibrosis (PMF) is a subtype of BCR-ABL1 negative myeloproliferative neoplasm. Its characteristic features include clonal myeloproliferation, dysregulation of kinase signaling pathway, abnormal release of cytokines leading to fibrosis in the bone marrow, osteosclerosis, and extramedullary hematopoiesis. Approximately 20% of deaths occur because of disease progression, but death may also result occur because of cardiovascular complications or as a consequence of either infection or bleeding. The only and curative option for PMF is allogeneic hematopoietic stem cell transplant (allo-HSCT); however, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib is highly effective in reducing constitutional symptoms and spleen volume, and has been found to improve survival. Ruxolitinib decreases the activity of type I T-helper cells, leading to decreased release of cytokines including tumor necrosis factor-α, interleukin-1 (IL-1), IL-6, interferon-γ, and production of IL-12, which can be a risk factor for opportunistic infections. In this report, we describe three cases of tuberculosis reactivation shortly after initiation of ruxolitinib therapy followed by a literature review.

Bowel Perforation Secondary to Ponatinib Treatment in a Chronic Myelogenous Leukemia Patient: A Case Report.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm of hematopoietic cell origin.It arises from the translocation of chromosomes 9 and 22, with resultant Philadelphia (Ph+) chromosome that contains the BCR-ABL1 gene. CML has three phases: the chronic phase, the accelerated phase, and blast crisis. Tyrosine kinase inhibitors are used as the targeted therapy of CML. This report is about a 30-year-old male who is normally fit and well with no past medical history of note. He was diagnosed previously with CML and presented in a blast crisis. With this blast crisis at presentation, the patient was started on ponatinib. After 12 days from starting ponatinib, the patient presented with abdominal pain and vomiting. Imaging showed small bowel perforation, which required immediate surgery. The patient's cardiovascular risk for such event was low and ponatinib was thought to be the most likely cause of this complication; thus, higher-risk patients for such ischemic events should be observed closely.

Impact of age and induction therapy on outcome of 180 adult patients with acute myeloid leukemia; retrospective analysis and literature review.

The prognosis of acute myeloid leukemia (AML) remains poor. Among 180 patients, the median age was 53 (14-88) years. The overall 2-year disease free survival (DFS) was 28.6% (+/- 3.4), 47.7% (+/- 6.6%) for ≤ 40, 23.6% (+/- 5.8%) for 41-60 and 11.7% (+/- 4.2%) for ≥61 (p< 0.0001). The overall 2-year survival (OS) was 45.3% (+/- 3.8%), 78.6% (+/- 5.5%) for ≤40, 43.5% (+/- 6.9%) for 41-60 and 15.8% (+/- 4.8%) for ≥61 (p< 0.0001). Induction outcome of ≥61 was best in high dose chemotherapy (HDC) group (p < 0.0001). Only those ≤40 had durable DFS and OS. HDC appears to improve the outcome of older AML patients.

Spontaneous Subgaleal Hematoma in a Sickle Cell Disease Patient: A Case Report.

Sickle cell disease (SCD) is one of the most commonly inherited conditions on the Arabian Peninsula. We report a case of a 17-year-old boy, who had previously been diagnosed with SCD and glucose-6-phosphate dehydrogenase (G6PD) deficiency and recently presented to our hospital with spontaneous subgaleal hematoma (SGH), which was managed conservatively. We also present a literature review on the topic of spontaneous intra- and/or extra-cranial bleeds.

Interim Functional Imaging Is an Independent Predictor of Progression-free Survival in Advanced Classical Hodgkin Lymphoma - A Real-world Analysis.

BACKGROUND: Response-adapted therapy in advanced classical Hodgkin lymphoma (cHL) using interim functional imaging (IFI) is under active investigation. PATIENTS AND METHODS: We retrospectively examined patients with advanced cHL receiving 2 front-line regimens stratified by IFI results at our institution. Time to endpoint analysis was estimated using the method of Kaplan-Meier with log ranks. Cox regression modeling was computed for multivariable analysis. RESULTS: A total of 124 patients with advanced cHL with a median follow up of 40.9 months were included. A total of 84 (67.7%) received ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), whereas the remaining 40 (32.3%) received ABVD/eBEACOPP (escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). A positive IFI was seen in 36 (29%) patients. The corresponding 3-year progression free survival (PFS) stratified by IFI was 81.7% (95% confidence interval [CI], 70.1%-88.8%) versus 48.3% (95% CI, 30.4%-64.1%) (P < .0001) for patients with negative or positive scan, respectively. Escalation to eBEACOPP from ABVD following a positive IFI resulted in a significantly higher 3-year PFS at 58.7% (95% CI, 0.3-0.79) versus 39.7% (95% CI, 0.18-0.61) respectively (P = .00015). Overall survival (OS) was similar across the groups (P = .44) irrespective of therapy received. At multivariable analysis, IFI was the only predictor of PFS with a hazard ratio of 4.6 (95% CI, 1.9-10.8; P = .0008) whereas therapy escalation had a hazard ratio of 0.66 (95% CI, 0.14-3.4; P = .62). CONCLUSION: IFI is an independent predictor of PFS in advanced cHL and can guide therapeutic decisions in the real world. Given the inferior outcome seen in patients with a positive IFI, novel approaches of therapy are warranted.

Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study.

AIMS: The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome - coronavirus (MERS-CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology. METHODS AND RESULTS: We analysed the post-mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T cell lymphoma, who acquired MERS-CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles. CONCLUSION: The results highlight the pulmonary and extrapulmonary pathological changes of MERS-CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS-CoV in kidney.

Reducing Central Venous Catheter Use in Peripheral Blood Stem Cell Donation: Quality Improvement Report.

Peripheral blood stem cell (PBSC) collection from donors through apheresis has become the main source of stem cells for hematopoietic stem cell transplantation. This procedure requires a high blood flow venous access. A peripheral venous catheter (PVC), compared to a central venous catheter (CVC), is considered to provide safer venous access. However, initially at our institution, King Abdul-Aziz Medical City - Riyadh, a CVC was frequently used (72%). A quality improvement multidisciplinary team has been formed to conduct a systematic quality performance analysis to evaluate the current process of collecting donor PBSCs with the aim to reduce CVC use to less than the international benchmark (20%). A quality improvement methodology, rapid cycles of plan-do-study-act (PDSA), was used to test a set of initiatives. An Intravenous (IV) team assessed the donor's venous access and inserted an appropriate PVC when feasible. This project ran over 16 months with 42 adult donors undergoing PBSC collection. During the first PDSA cycle, 1 CVC was inserted for every 4 donors. In the second PDSA cycle, 1 CVC was inserted for every 8 apheresis donations. In the third PDSA cycle, no CVC was used for 30 apheresis donations. The targeted stem cell dose was collected successfully in one apheresis session in all donors assigned for PVC access with no complications. A significant reduction of CVC use from 72% to 0% was achieved. This quality improvement project demonstrated that a successful apheresis procedure can be achieved easily and safely in the majority of PBSC donors preventing the potential adverse events associated with CVCs. The interdisciplinary collaboration between the IV team, apheresis and clinical hematology teams was paramount to optimize the safe care of donors.