Management of adult acute lymphoblastic leukemia in the Gulf Cooperation Council (GCC) countries: A consensus report from the GCC Adult ALL Working Group.

Leukemia burden is growing in the Gulf Council Cooperation (GCC) countries. Nonetheless, there is no unified protocol for managing adult acute lymphoblastic leukemia (ALL) patients in the GCC-countries. Therefore, the GCC Adult-ALL Treaters working group developed this consensus to address the adult-ALL treatment protocols in the GCC-countries and related toxicities' management. Besides, the consensus aimed to highlight the current unmet needs and treatment gaps and provide recommendations to optimize adult-ALL care and patient-centered communication. A three-step modified Delphi method to develop evidence-based recommendations through two-voting rounds and in-between virtual meetings are used in the manuscript development. A 12 experts' panel from five GCC-countries and two international experts were invited to participate in this consensus. This consensus consisted of 35-statements that highlighted the experts' recommendations to optimize ALL adults' care in the first line setting and manage pediatric or pediatric-inspired regimens-related toxicities. Besides, guidance was provided for future research direction and improve patient-centered communication. In conclusion, the adult-ALL management landscape is evolving, and the current evidence highlights better response and survival outcomes with pediatric or pediatric-inspired regiments. Therefore, protocols are needed to optimize the adult-ALL management in the GCC and tailored clinical-trials findings according to the GCC patients' characteristics and local-healthcare infrastructure.

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.

Lupus Anticoagulant-Hypoprothrombinemia Syndrome and Pseudotumor Cerebri as an Initial Presentation of Systemic Lupus Erythematosus in a 16-Year-Old Male Patient: A Case Report and Literature Review.

BACKGROUND Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is an exceptionally rare disease caused by prothrombin antibodies, resulting in reduced factor II levels. This disease can present with significant bleeding and is usually associated with autoimmune disorders, particularly systemic lupus erythematosus (SLE). There are currently no guidelines for the treatment of LAHPS, and corticosteroids remain the criterion standard therapy. Pseudotumor cerebri is a disease that involves an idiopathic rise in intracranial pressure in association with papilledema. The coexistence of pseudotumor cerebri with SLE is rare, with an overall incidence of 0.7%. CASE REPORT A 16-year-old male initially presented to our hospital with nausea, headaches, and decreased visual acuity. He was diagnosed with pseudotumor cerebri based on the findings of papilledema and a raised opening pressure on lumbar puncture. Three months later, he presented with macroscopic hematuria and persistent epistaxis. Further investigation revealed a prolonged activated partial thromboplastin time and prothrombin time, along with positive LA and reduced Factor II levels, resulting in a diagnosis of LAHPS. The patient received a dose of 1 mg/kg/day of prednisolone along with hydroxychloroquine, and he had a complete recovery with cessation of bleeding and normalization of laboratory parameters. CONCLUSIONS We are reporting a case of pseudotumor cerebri with a further presentation of LAHPS in a patient found to have SLE. As both associations are rare in the presence of SLE, it is vital to recognize them early to initiate adequate management and intervention to avoid life-threatening complications.

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.

Erdheim-Chester Disease Successfully Treated with Front-Line Single-Agent Dabrafenib.

BACKGROUND Erdheim-Chester disease (ECD) is a clonal disease characterized by histiocytic infiltration of multiple organ systems. As ECD is a rare disorder with variable presentations, its diagnosis and management can present a significant clinical challenge. The diagnosis of ECD requires several clinical, radiological, and histological criteria. Since approximately 75% of ECD patients harbor a mutation in the proto-oncogene BRAF V600E, inhibition of BRAF activation by BRAF inhibitors has significantly improved the management of ECD. Vemurafenib was approved by the U.S. Food and Drug administration for treatment of BRAF-mutated ECD. Another BRAF inhibitor, dabrafenib, has been used in some cases as a single agent and was associated with a lower toxicity profile. CASE REPORT We report the case of a 30-year-old Saudi Arabian woman who initially presented with a history of diffuse abdominal pain and fever. The patient had elevated inflammatory markers, and radiological investigations revealed hypermetabolic regions in the frontoparietal brain lobe, anterior pericardium, kidneys, and the anterior abdominal wall. Histological investigations from the right perinephric soft-tissue mass revealed foamy histiocytes associated with mild chronic inflammation. Furthermore, BRAF V600E was mutated in the biopsy sample, leading to a diagnosis of BRAF-mutated ECD. The patient began single-agent dabrafenib therapy at 75 mg twice daily and experienced an excellent clinical and radiological response with no reported toxicity. CONCLUSIONS Single-agent dabrafenib is effective and well tolerated among ECD patients; therefore, it might be considered as a first-line option for the treatment of BRAF-mutated ECD.

Reducing Futile Acute Care Services for Terminally Ill Patients With Cancer: The Dignity Project.

PURPOSE: Patients with terminal diseases frequently undergo interventions that are futile and may be detrimental to their quality of life. We conducted a quality improvement project aimed to reduce the utilization of futile acute care services (ACSs) for patients with cancer treated with a palliative intent. METHODS: A multidisciplinary team reviewed the records of terminally ill patients with cancer who died between November 2017 and May 2018, during their admission at our institution. The review aimed to assess the magnitude of improper utilization of ACSs and admission to the intensive care unit (ICU). Lack of timely documentation of the goals of care (GOCs) was the main reason for this problem. We defined timely documentation as the availability of electronic documentation of patients' GOC before the need for ACSs. Interventions were implemented to improve the process; postintervention data were captured and compared with the baseline data. RESULTS: After the delivery of staff education and the implementation of mandatory documentation of the GOCs in the healthcare electronic record system, the timely documentation of the GOCs for patients with a palliative intent increased significantly from 59% at baseline to 83% in the postintervention phase. The impact of this intervention led to a decrease in admissions to the ICU from 26% to 12% and an estimated annual cost saving of $777,600 in US dollars. CONCLUSION: Our interventions resulted in improved documentation of the GOCs and decrease in the utilization of ACSs including ICU admissions and the associated cost.

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.

Role of Allogeneic HCT as Postremission Therapy for Transplant-Eligible Adult Lymphoblastic Leukemia/Lymphoma After Frontline Hyper-CVAD.

BACKGROUND: Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with cytarabine and methotrexate (hyper-CVAD) is a commonly used regimen in adults with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Adult patients fit for pediatric-inspired protocols have an excellent outcome with chemotherapy alone. However, it is unclear whether patients receiving hyper-CVAD should undergo allogeneic hematopoietic cell transplantation (HCT) as postremission therapy. Our aim was to examine the role of HCT at first complete remission (CR1) in adult ALL/LBL after hyper-CVAD. PATIENTS AND METHODS: Adult patients with newly diagnosed ALL/LBL receiving frontline hyper-CVAD from 2008 to 2018 were identified and records retrospectively extracted. RESULTS: A total of 85 patients were identified and included for further analysis. The median (range) age was 23 (14-68) years, and 56 (66%) were male. A total of 24 (28%) had adverse cytogenetics, and 48 (56%) had at least one risk factor. All patients received hyper-CVAD as induction; induction failure was seen in 10 (12%). A total of 38 patients continued the hyper-CVAD course, while the remaining 47 received HCT in CR1. Three-year event-free survival (EFS) and overall survival for the entire cohort were 51.4% and 61.6%, respectively. Median follow-up of alive patients was 39.9 (3.8-123.8) months. At multivariable analysis for EFS, induction failure was associated with worse outcome (hazard ratio [HR], 4.8; 95% confidence interval [CI] 1.7-13.7; P = .003), whereas HCT in CR1 improved outcome (HR, 0.42; 95% CI 0.18-0.97; P = .044). Furthermore, HCT in CR1 was the only prognostic factor for overall survival (HR, 0.3; 95% CI 0.11-0.85; P = .023). CONCLUSION: HCT at CR1 resulted in a favorable EFS and overall survival in ALL/LBL patients after hyper-CVAD frontline therapy. Given that hyper-CVAD is a widely used protocol for adult patients, further examination of this observation is warranted.

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.

Isolated Bone Marrow Non-Langerhans Cell Histiocytosis Preceding RUNX1-Mutated Acute Myeloid Leukemia: Case Report and Literature Review.

OBJECTIVES: The prevalence of concomitant myeloid neoplasms was recently reported to be unexpectedly high among adults without non-Langerhans cell histiocytosis (non-LCH); however, the coexistence of non-LCH with RUNX1 genetic aberration has not been reported previously. METHODS: Herein, we report a 23-year-old woman with severe pancytopenia diagnosed with non-LCH following presentation with pancytopenia and marrow examination showing histiocytosis positive for CD45, CD68, CD136, and lysozyme but negative for CD1a, langerin, and S100. RESULTS: Whole-exome sequencing showed RUNX1 mutation and NF1 mutation. In the ensuing 6 months, she developed hepatosplenomegaly, and repeat bone marrow evaluation was diagnostic of acute myeloid leukemia (AML). Repeat mutational analysis showed again presence of RUNX1 mutation. She underwent induction therapy but died of septic shock. CONCLUSIONS: The demonstration of RUNX1 mutation in both non-LCH and AML bone marrow specimens at differing time points is suggestive of a biologic association of both distinct disease entities.

Erdheim-Chester Disease with No Skeletal Bone Involvement and Massive Weight Loss.

Erdheim-Chester disease (ECD) is a rare type of non-Langerhans cell histiocytosis, with only 550 cases reported worldwide. ECD is characterized by diffuse histiocytic infiltration of multiorgans. The age of presentation of this disease is typically between 40 and 70 years. Bone disease is the most common symptom, as unique radiological findings of long bone sclerosis occur in 96% of cases. Furthermore, BRAF V600E mutation is detected in 60% of ECD cases. In this manuscript, we are describing a unique case of ECD; the patient is younger than most reported cases and has no bone pain or any skeletal involvement. This patient has unintentionally lost about 50% of his body mass and is suffering from progressive cerebellar manifestations with radiological evidence of cerebellar atrophy, in contrast to the usual ECD manifestation of cerebellar infiltration. In addition, the patient has cardiac, retroperitoneal, and perinephric involvement, but he retains his sexual drive and fertility. A tissue biopsy from the retroperitoneal mass displayed typical morphological and immunohistochemical features of ECD, and BRAF V600E mutation was detected. He was treated with pegylated interferon alpha, but his disease progressed and the treatment was changed to vemurafenib to which he had an excellent response at 6 weeks.

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.

The effect of lifestyle modification on severity of constipation and quality of life of elders in nursing homes at Ismailia city, Egypt.

BACKGROUND: Constipation has a significant impact on the quality of life (QOL). Lifestyle modification is widely accepted and recommended by experts as first-line therapy. AIM: This study aimed at using education on lifestyle modification to improve the QOL of the elderly in nursing homes suffering from functional constipation (FC). MATERIALS AND METHODS: This study was conducted in nursing homes in Ismailia city, Egypt. It involved 23 elderly patients suffering from FC, who were randomly selected according to the sample equation. They fulfilled the inclusion criteria of being ≥60 years age and according to Rome II criteria. Participants completed personal characteristics and lifestyle questionnaire, the Patient Assessment of Constipation Symptom questionnaire (PAC-SYM) to assess the severity of symptoms, and the Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) to assess pre- and post-intervention. The intervention was conducted in three sessions, of 30 min each, 2 weeks apart using group discussions to educate the sample about dietary pattern, fluid intake, regular physical activity, and the use of laxatives. STATISTICAL ANALYSIS: Data were analyzed using a statistical package for social sciences (SPSS version 20). RESULTS: The lifestyle modification education on constipation significantly reduced the severity of symptoms as measured by PAC-SYM, including its total score and subscores (P < 0.001). It also improved the QOL of elderly suffering from constipation as measured by PAC-QOL and reduced total scores of dissatisfaction (P = 0.001) with the exception of the psychosocial subscale. It also significantly increased the satisfaction subscale of PAC-SYM (P < 0.001). CONCLUSION: Education on lifestyle modification leads to an improvement in the severity of the symptoms of constipation and the QOL of the elderly in nursing homes.