Mohsen Alzahrani

Primary CNS lymphoma presenting as fever of unknown origin

We report a case of fever of unknown origin in an immunocompetent patient as the first manifestation of primary central nervous lymphoma. To our knowledge this is the first reported case in the literature of this association. We recommend brain imaging to be considered in patients presenting with fever of unknown origin and no apparent diagnosis after extensive investigation.

ABO and Rh blood group genotypes in a cohort of Saudi stem cell donors

The ABO and rhesus (Rh) blood group antigens are the most frequently studied genetic markers in a large group of people. Blood type frequencies vary in different racial/ethnic groups. Our objective was to investigate the distribution of the ABO and rhesus (Rh) blood groups by molecular typing method in a population of Saudi stem cell donors. Our data indicate that the most common blood group in our population is group O followed by group A then group B, and finally, the least common is group AB.

Peripheral hematopoietic stem cell mobilization utilizing growth factors in donors with sickle cell trait is safe and effective

Allogeneic hematopoietic stem cell transplantation (HCT) is a curative treatment for sickle cell disease (SCD). However, the majority of patients in need of such therapy are ineligible due to underlying comorbidities or lack of available donor . Recent literature attempting to expand the donor pool via utilizing matched unrelated donors or cord blood units was hampered by significant toxicity due to graft vs. host disease (GVHD) or graft failure [1, 2]. Furthermore, although peripheral stem cell mobilization using granulocyte colony stimulating factor (GCSF) is widely used in allogeneic HCT, patients with SCD are prone to significant risks with GCSF including splenic rupture or death, in part due to precipitation of vaso-occlusive crises (VOC) [3, 4]. Although sickle cell trait (SCT) is a relatively benign disorder related to SSD, there are reports of VOC in such patients during conditions of severe stress [5]. There is paucity in the literature with regards to the safety of GCSF in SCT carriers; therefore our aim from this analysis was to examine the safety and efficacy of utilizing growth factors in donors with SCT. After due IRB approval, allogeneic donors for sibling recipients with SCD were identified and medical records retrospectively extracted. A sickle cell screen was performed and if positive, high-performance liquid chromatography (HPLC) was done. All donors were interviewed for symptoms post mobilization and a survey was completed to inquire about related adverse effects, graded by the common terminology criteria for adverse events (CTCAE) v.4.0. GCSF was administered at a dose of 10 mcg/kg rounded to the nearest vial size for 5 days followed by high flow apheresis on the fifth day. CD34 enumeration was measured on days 4 and 5. At our center, the ideal collection target was ≥10 × 10/kg CD34 cells of recipient weight to allow safe engraftment in the context of SCD. Stem cells were infused on the same day of collection without cryopreservation. Categorical and continuous variables were compared using Pearson’s chi-squared and Wilcoxon/ Kruskal–Wallis, respectively. Analysis was computed using JMP Pro Version 11 (SAS Institute, Cary, NC, USA) software. A total of 27 consecutive donors were identified during the period between December 2014 and November 2017. Among the donors, 14 (52%) were SCT carriers. The cohort was stratified based on the presence of SCT and their corresponding baseline characteristics were similar with regards to age, gender, weight, CMV status, GCSF dose/kg used and peripheral CD34 and blood counts on collection day as shown in Table 1. There was a trend toward multiple day collections in control donors (p= 0.078). Donor reported symptoms on the post mobilization survey are shown in Table 2. There was no significant difference with regards to incidence or severity of reported symptoms; specifically, fever/chills, fatigue, nausea or vomiting, insomnia, headache, myalgia, arthralgia, abdominal pain or pain elsewhere. The incidence of any grade symptoms was also comparable. The results remained unchanged when comparing grade I/II vs. III or grade I vs. II/III (data not shown). The majority of donors reported symptoms and ~80% required analgesia to control pain (two required codeineacetaminophen). The median duration of pain (range) was similar between SCT donors 3 days (2–10) and healthy donors 4 (2–5) (p= 0.77). None of the donors developed sickle cell-related complications, thrombosis or required transfusion support. Furthermore, there were no serious or * Moussab Damlaj damlajmo@ngha.med.sa

Indications, retrieval rate, and complications of inferior vena cava filters: Single-center experience in Saudi Arabia

BACKGROUND: Inferior vena cava (IVC) filter is indicated in patients with acute venous thromboembolism (VTE) in whom therapeutic anticoagulation is contraindicated. While prophylactic insertion of an IVC filter may be considered for patients at high risk of VTE, there are significant differences between clinical guidelines on the role of IVC filters. These discrepancies have arisen predominantly because of the paucity of data on the efficacy and safety of IVC filters. We, therefore, evaluated the indications for filter insertion, the rate of filter retrieval and complications in patients who received IVC filters at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. METHODS: A descriptive, retrospective review of electronic- and paper-based medical records was performed. Consecutive sampling was used to study all adult patients who received an IVC filter at KAMC between 2007 and 2016 and met the inclusion criteria. RESULTS: A total of 382 IVC filters were inserted. 113 patients (30%) had an acute VTE and a contraindication to anticoagulation while 53 patients (14%) received an IVC filter in the absence of VTE (i.e., prophylactic). Only 124 (32.5%) IVC filters were eventually retrieved. The most common reason for nonretrieval was the need for permanent filtration (155, 60%). Thrombotic complications developed in 72 (19%) patients; nine patients had fatal pulmonary embolism. CONCLUSION: The insertion of IVC filters in this cohort was associated with low retrieval rate and relatively high incidence of thrombotic complications. Follow-up of patients is required to detect IVC filter-related complications and to increase retrieval rate.

Lymphocyte recovery is an independent predictor of relapse in allogeneic hematopoietic cell transplantation recipients for acute leukemia

AIM To examine the optimal absolute lymphocyte count (ALC) cut-off utilizing receiver operator characteristics (ROC) in addition to graft characteristics associated with early ALC recovery. METHODS Patients who received T-cell replete peripheral hematopoietic cell transplantation (HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes. RESULTS A total of 72 patients met the inclusion criteria and were analyzed. Optimal ALC cut-off was established to be on day 14 (D14) with ALC > 0.3 × 109/L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9% (P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery (ELR) group at 70% vs 27%, respectively (P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27 (0.05-0.94, P = 0.038). CONCLUSION ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count.

Pre-autologous transplantation PET|[sol]|CT using Deauville criteria is an independent predictor of progression in relapsed refractory classical Hodgkin lymphoma

High-dose salvage chemotherapy followed by haematopoietic stem cell transplantation (HCT) is the standard of care in transplant eligible relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL).1 Approximately, half of patients receiving HCT will achieve long-term remissions, but relapse remains the most common cause of treatment failure. A number of prior studies investigated the value of pre-HCT positron emission tomography (PET) scan as a predictor of outcome. Considerable heterogeneity is noted within these studies due to methodology of PET interpretation, timeline of the scan prior to HCT and whether further clinical decisions were based on the scan results.2, 3, 4, 5 In light of the above, we examined the impact of pre-HCT PET/CT graded on the five-point scale Deauville criteria on the post-HCT outcome.

CD95-mediated apoptosis in Burkitt's lymphoma B-cells is associated with Pim-1 down-regulation.

B-cells of the high-grade non-Hodgkin lymphoma Burkitts lymphoma (BL) overexpress survival oncoproteins, including the proviral integration site for Moloney murine leukaemia virus kinase (Pim)-1, and become apoptosis resistant. Activated death receptor CD95 after ligation with anti-CD95 monoclonal antibody (mAb) resulted in the regression of BL via induction of apoptosis, suggesting a decrease of survival protein expression. Here, CD95-mediated apoptotic pathways in BL B-cell lines (Raji and Daudi) following treatment with anti-CD95 mAb was investigated with the cause-and-effects on pim-1 gene expression, in comparison with leukemic cell line (K562) used as CD95-negative cells. Immunohistochemical staining for CD95 and Pim-1 was performed, and the effects of anti-CD95 mAb on apoptotic signalling using western blotting, on caspase activity and cell survival of BL B-cell and leukemic cell lines were determined. We showed that Raji cells expressed more CD95 receptors than Daudi cells. Half of each population underwent apoptosis accompanied by decreased cell viability after anti-CD95 mAb treatment. Distinct extrinsic and intrinsic CD95-mediated apoptotic pathways in Raji and Daudi cells were revealed by high caspase activity and mitochondrial outer membrane permeabilization, respectively. We observed decreased Pim-1 transcript and protein expression levels with increased heat-shock protein (Hsp)70 and decreased Hsp90 expression in anti-CD95 mAb-treated cells. Throughout the study, K562 cells did not undergo apoptosis upon anti-CD95 mAb treatment. Pim-1 knockdown following to stable transfection with plasmid vectors induced apoptosis and decreased viability of BL and K562 cells. Therefore, CD95-mediated apoptosis induces Pim-1 down-regulation in BL B-cells, but Pim-1 down-regulation cannot fully eradicate BL and leukaemia.

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 donors 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.