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Background: During the coronavirus disease (COVID-19) pandemic, patients with cancer in rural settings and distant geographical areas will be affected the most by curfews. Virtual management (telemedicine) has been shown to reduce health costs and improve access to care.Objective: The aim of this survey is to understand oncologists' awareness of and views on virtual management, challenges, and preferences, as well as their priorities regarding the prescribing of anticancer treatments during the COVID-19 pandemic.Methods: We created a self-administrated electronic survey about the virtual management of patients with cancer during the COVID-19 pandemic. We evaluated its clinical sensibility and pilot tested the instrument. We surveyed practicing oncologists in Gulf and Arab countries using snowball sampling via emails and social media networks. Reminders were sent 1 and 2 weeks later using SurveyMonkey.Results: We received 222 responses from validated oncologists from April 2-22, 2020. An awareness of virtual clinics, virtual multidisciplinary teams, and virtual prescriptions was reported by 182 (82%), 175 (79%), and 166 (75%) respondents, respectively. Reported challenges associated with virtual management were the lack of physical exam (n=134, 60%), patients' awareness and access (n=131, 59%), the lack of physical attendance of patients (n=93, 42%), information technology (IT) support (n=82, 37%), and the safety of virtual management (n=78, 35%). Overall, 111 (50%) and 107 (48%) oncologists did not prefer the virtual prescription of chemotherapy and novel immunotherapy, respectively. However, 188 (85%), 165 (74%), and 127 (57%) oncologists preferred the virtual prescription of hormonal therapy, bone modifying agents, and targeted therapy, respectively. In total, 184 (83%), 183 (83%), and 176 (80%) oncologists preferred to continue neoadjuvant, adjuvant, and perioperative treatments, respectively. Overall, 118 (53%) respondents preferred to continue first-line palliative treatment, in contrast to 68 (30%) and 47 (21%) respondents indicating a preference to interrupt second- and third-line palliative treatment, respectively. For administration of virtual prescriptions, all respondents preferred the oral route and 118 (53%) preferred the subcutaneous route. In contrast, 193 (87%) did not prefer the intravenous route for virtual prescriptions. Overall, 102 (46%) oncologists responded that they would "definitely" prefer to manage patients with cancer virtually.Conclusions: Oncologists have a high level of awareness of virtual management. Although their survey responses indicated that second- and third-line palliative treatments should be interrupted, they stated that neoadjuvant, adjuvant, perioperative, and first-line palliative treatments should continue. Our results confirm that oncologists' views on the priority of anticancer treatments are consistent with the evolving literature during the COVID-19 pandemic. Challenges to virtual management should be addressed to improve the care of patients with cancer. [ABSTRACT FROM AUTHOR]

Objectives: Sickle cell disease (SCD) is an inherited disorder that causes lifelong complications, substantially impacting the physical and emotional well-being of patients and their caregivers. Studies investigating the effects of SCD on quality of life (QOL) are often limited to individual countries, lack SCD-specific QOL questionnaires, and exclude the caregiver experience. The SHAPE survey aimed to broaden the understanding of the global burden of SCD on patients and their caregivers and to capture the viewpoint of healthcare providers (HCPs)., Methods: A total of 919 patients, 207 caregivers, and 219 HCPs from 10, 9, and 8 countries, respectively, answered a series of closed-ended questions about their experiences with SCD., Results: The symptoms most frequently reported by patients were fatigue/tiredness (84%) and pain/vaso-occlusive crises (71%). Patients' fatigue/tiredness had one of the greatest impacts on both patients' and caregivers' QOL. On average, patients and caregivers reported missing 7.5 days and 5.0 days per month, respectively, of school or work. HCPs reported a need for effective tools to treat fatigue/tiredness and a desire for more support to educate patients on long-term SCD-related health risks., Conclusions: The multifaceted challenges identified using the SHAPE survey highlight the global need to improve both patient and caregiver QOL., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Objective: Sickle cell disease (SCD) is a common hereditary hemoglobin disorder worldwide. One of the main treatments for patients with SCD is the requirement for blood transfusions. Posttransfusion alloimmunization with red blood cell (RBC) antigens continues to be a major risk factor for SCD. The objective of this study was to determine the rate, nature, and risk factors of red cell alloimmunization among pediatric patients with SCD in our center and compare our results with published reports from Saudia Arabia SA, regional countries, and some international countries., Materials and Methods: A retrospective chart review of patients with SCD at King Abdulaziz Medical City-Jeddah, between 2008 and 2019 was performed. Demographic characteristics and transfusion histories were recorded. Blood samples were analyzed for alloimmunization using immunohematologic techniques., Results: In total, 121 patients were analyzed. Alloantibodies were detected in 21 patients (17.4%) and were mostly single in 15 patients (71.4%), anti-K (23.7%), anti-E (19.0%), and anti-S (9.5%). The other 6 patients (28.6%) had multiple alloantibodies, especially the combination of anti-C and anti-K (9.5%) and the combination of anti-C and anti-E (9.5%). Alloantibody levels were significantly higher in patients with frequent hospital admissions (>5 times annually), those who had an exchange blood transfusion, those younger than 3 years old, and those who received a larger number of blood units ( P ≤0.05)., Conclusion: The rate of RBC alloimmunization is determined and considered relatively low compared with that in other nations. Matching for extended RBC antigens to include ABO, RH (D, C, c, E, e), K, Fy a , Fy b , Jk a , and Jk b antigens in the screening panel for donors and recipients is highly recommended to ensure better transfusion practices and avoid transfusion-related complications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background Sickle cell disease (SCD) is a common hematological disorder with a high prevalence in Saudi Arabia. Despite that, limited studies are available in our region regarding cardiovascular complications. Objectives The objective of the current study was to estimate the prevalence of cardiovascular complications among children with SCD. Design This was a cross-sectional study. Setting The study took place at a single tertiary-care center in Jeddah, Saudi Arabia. Materials and methods The study reviewed 126 electronic records of pediatric patients up to 16 years old diagnosed with SCD between January 2008 and December 2019 in King Abdulaziz Medical City (KAMC) in Jeddah, Saudi Arabia. Of these, 54 patients had a previous echocardiogram evaluation and were eligible for the study. Main outcomes measures The study identified cardiovascular complications in pediatric sickle cell patients. Sample size The study included a total of 54 pediatric sickle cell patients. Results The mean age was 11.9 (3.48) years, the male-to-female ratio was 2:1, the majority (94.4%) had the HbSS-HbSβ0 genotype, the mean baseline hemoglobin F (fetal hemoglobin) was 20.30 (9.03%), and the clinical severity score was severe in 19 (35.2%) and mild/moderate in 35 (64.8%) patients. Cardiovascular complications occurred in 32 (59.3%) patients. Increased systolic blood pressure was detected in 10 (18.5%) patients. Echocardiography showed left ventricular dilatation in nine (16.7%) patients, tricuspid valve insufficiency in six (11.1%) patients, mitral valve insufficiency in four (7.4%) patients, hyperdynamic left ventricle in one (1.9%) patient, and pulmonary hypertension in one (1.9%) patient. Long QTc interval was noticed in three (5.6%) and cardiomegaly was detected in 18 (33.3%) patients. Conclusion Cardiovascular complications occurred at a high frequency in our pediatric population despite high baseline hemoglobin F levels. Early evaluation and continuous monitoring are important for early intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Waggass et al.)

Introduction: The oral cavity is one of the most common sites impacted by hematopoietic stem cell transplantation (HSCT) with acute complications including mucositis, bleeding, salivary gland dysfunction, infection, and taste alteration. These complications may result in significant morbidity and can negatively impact outcomes such as length of stay and overall costs. As such, oral care during HSCT for prevention and management of oral toxicities is a standard component of transplant protocols at all centers. The objective of this study was to evaluate the current oral care practices for patients during HSCT at different transplant centers within the Eastern Mediterranean region., Material and Methods: An internet-based survey was directed to 30 transplant centers in the Eastern Mediterranean region. The survey included five sections asking questions related to (1) transplant center demographics; (2) current oral care protocol used at the center and type of collaboration (if any) with a dental service; (3) use of standardized oral assessment tools and grading systems for mucositis; (4) consultations for management of oral complications; and (5) oral health needs at each center. Data are presented as averages and percentages., Results: A total of 16 responses from 11 countries were collected and analyzed, indicating a response rate of 53%. Eight centers reported that a dentist was part of the HSCT team, with four reporting oral medicine specialists specifically being part of the team. Almost all centers (15/16; 93%) had an affiliated dental service to facilitate pre-HSCT dental clearance with an established dental clearance protocol at 14 centers (87%). Dental extraction was associated with the highest concern for bleeding and the need for platelet transfusion. With respect to infection risk, antibiotic prophylaxis was considered in the setting of low neutrophil counts with restorative dentistry and extraction. All centers provide daily reinforcement of oral hygiene regimen. The most frequently used mouth oral rinses included sodium bicarbonate (68%) and chlorhexidine gluconate (62%), in addition to ice chips for dry mouth (62%). The most frequently used mucositis assessment tools were the World Health Organization scale (7/16; 43%) and visual analogue scale for pain (6/16; 37%). Mucositis pain was managed with lidocaine solution (68.8%), magic mouth wash (68.8%) and/or systemic pain medications (75%)., Conclusions: Scope and implementation of oral care protocols prior to and during HSCT varied between transplant centers. The lack of a universal protocol may contribute to gaps in oral healthcare needs and management for this group of patients. Further dissemination of and education around available oral care guidelines is warranted., Clinical Relevance: Considering oral care during HSCT a standard component of transplant protocols, the current study highlights the common oral care practices for patients at centers within the Eastern Mediterranean region.

Introduction Tumor lysis syndrome (TLS) is a life-threatening metabolic abnormality. The incidence of TLS depends on the underlying malignancy. In a recent analysis of hematological malignancy, the incidence of clinical TLS in children was 3.8%, laboratory TLS 46.2%, and hyperphosphatemia 32.7%. Sevelamer is effective for the treatment of hyperphosphatemia associated with renal failure; however, there is no clear data that it has the same effect in treating hyperphosphatemia with TLS. Methods This was a retrospective study among children aged ≤14 years with hematological malignancy who developed TLS and received sevelamer to treat hyperphosphatemia at Princess Norah Oncology Center, King Abdulaziz Medical City (KAMC) in Jeddah from January 2012 to December 2016. Results A total of 34 patients received sevelamer. The majority was male (64%), with a median age of six years. The median sevelamer dose per day was 1600 mg, while the median duration of use was two days. Phosphate level was significantly decreased at different times (24 hours, 48 hours, and 72 hours) during sevelamer usage, p-value <0.001. Conclusion In our study, the use of sevelamer resulted in a significant decrease in phosphate levels. This finding further consolidates the efficacy of sevelamer in treating hyperphosphatemia with TLS. However, further research into the drug's kinetics is recommended., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Al Blewi et al.)

Objective: To estimate the prevalence of tuberculosis (TB) infection among patients receiving cancer chemotherapy and to identify risk factors for latent TB reactivation., Methods: A cross-sectional study was conducted at a tertiary care center in Jeddah, Saudi Arabia. Patients were surveyed for TB risk factors, their records were reviewed for previous TB infection or disease, and blood samples were collected for interferon-gamma release assays (IGRAs)., Results: A total of 203 patients were included. One hundred and twenty-five were females (62%). Median age was 52 years, and mean age was significantly higher in positive IGRA patients compared to negative IGRA (57.32 vs. 47.27; p = 0.009). Twenty-five patients (12.3%) had evidence of TB infection, 16 (68%) among them had a latent TB infection, while the rest received treatment for an active TB disease. The rate of active disease among cancer patients was 8 (3.9%). Additionally, 92% (23) of those with positive IGRA had solid cancers ( p = 0.007), and all active TB cases occurred in this group of solid cancers., Conclusion: TB prevalence was higher in chemotherapy patients compared to the general Saudi population. Patients with solid tumors and older age had a greater risk of developing the infection, signifying the importance of preventing TB and malignancy coexistence by initiating screening policies in cancer patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Aldabbagh et al.)

The management of Refractory/Relapsed B-cell Acute Lymphoblastic Leukemia (R/R ALL) remains challenging. Incorporating blinatumomab in R/R ALL treatment has shown encouraging results. We describe the outcome and predictors of response in children receiving blinatumomab as a bridge to definitive therapy. Immunoglobulin (Ig) G and viral serology before and after therapy were evaluated. Thirty-three patients that failed standard first-line treatments due to relapsed ALL ( n =  22), persistent minimal residual disease (MRD) ( n =  8), or refractory disease ( n =  3) received blinatumomab. Grade 2 toxicity occurred in 27.2% of patients. MRD remission (<0.01%) was achieved in 72.7% of patients. Pre-blinatumomab absolute lymphocyte count (ALC) and MRD/ALC ratio significantly associated with MRD-response. Patients with t(1;19) translocation had lower response rate, compared to all other cytogenetic categories ( p =  0.013). One-year event-free survival (EFS) and overall survival (OS) were 69.2% and 79.7%, respectively. Analysis of OS and EFS showed pre-blinatumomab MRD level, ALC, MRD/ALC ratio, t(1;19) , and post-blinatumomab MRD remission associated with survival. Following blinatumomab, 83% (15/18) of tested patients had low IgG levels. IgG seronegative status was observed in 83% (12/15) for varicella zoster, 35% (6/17) for herpes zoster, 18% (3/17) for cytomegalovirus, and 26% (5/17) for Epstein Barr virus. Blinatumomab produced encouraging results in children with R/R ALL and low disease burden bridging to definitive therapy. Incorporating baseline genetics and biomarkers may help identify subgroups likely to be responsive/resistant to therapy. Viral serological testing pre- and post-blinatumomab is recommended to optimize supportive and preemptive therapy.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2049936 .

Introduction: Emicizumab is a bispecific monoclonal antibody with the ability to bridge FIXa and FX, mimic FVIII, and restore normal hemostasis in patients with hemophilia A. Moreover, substantial evidence has shown that emicizumab-treated patients do not require monitoring, except before surgery or invasive procedures. However, introducing this novel drug to the market poses some challenges to physicians and clinical laboratories due to its interaction with conventional coagulation tests., Methods: Given the challenges and laboratory interactions posed by this novel drug, there is an unmet clinical need to develop clear recommendations for emicizumab laboratory monitoring to highlight which laboratory tests should be used, which tests should be avoided, and when these tests should be performed. These expert recommendations are essential to prevent inappropriate testing or misleading interpretations and reduce the extra costs of unnecessary monitoring., Results: A consensus meeting was conducted in December 2019, including top experts on hemophilia from Saudi Arabia, to discuss this issue., Conclusion: The experts agreed that, aPTT (activated Partial Thromboplastin Time)-based tests are not suitable for laboratory monitoring patients treated with emicizumab. Only FVIII chromogenic assays based on bovine FIX and FX proteins can be used to measure FVIII levels. They reviewed and recommended the type and time of testing for anti-factor VIII antibodies. Drug levels should be measured using the recommended test only when the anti-drug antibody (ADA) is clinically suspected and after excluding other causes (such as patient non-compliance)., Competing Interests: None., (AJBR Copyright © 2022.)

The prevalence of obstructive sleep apnea syndrome (OSAS) is elevated in some high-risk populations. Children with sickle cell disease (SCD) are known to have many comorbidities, including OSAS. The objectives of this study were to assess the prevalence of and risk factors for OSAS among children with SCD in two major tertiary health care facilities in Jeddah, Saudi Arabia. This multicenter cross-sectional study took place in two major tertiary health care facilities-King Abdulaziz University Hospital and King Khalid National Guard Hospital, Jeddah, Saudi Arabia. Children with SCD who were admitted between January 2010 and December 2017 were enrolled. The Pediatric Sleep Questionnaire (PSQ) was used to screen for OSAS. Data were collected from 150 children with SCD aged between 2 and 18 years. Eighty-five percent of the children had sickle cell anemia (SCA) with HbSS, and the rest had sickle beta-thalassemia (HbS/ß-thalassemia). Based on the PSQ, 33 of the 150 (22%) children had OSAS (score ≥ 7). The average score on the PSQ was 3.8/22 (± 3.8). A history of adenotonsillar hypertrophy was found to be a significant risk factor in bivariate and multivariate analyses [aOR 5.5; 95% CI 1.84-16.35 (P < 0.001)]. The odds of having OSAS were ninefold higher in children who had periodic limb movements than in those who did not after adjustment [95% CI 1.75-48.03 (P < 0.001)]. OSAS is a highly prevalent disease among children with SCD. Many factors were associated with OSAS in the bivariate analysis, including nationality, education level, a history of adenotonsillar hypertrophy, and a history of periodic limb movements., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To evaluate the effect of screening for sepsis using an electronic sepsis alert vs. no alert in hospitalized ward patients on 90-day in-hospital mortality., Methods: The SCREEN trial is designed as a stepped-wedge cluster randomized controlled trial. Hospital wards (total of 45 wards, constituting clusters in this design) are randomized to have active alert vs. masked alert, 5 wards at a time, with each 5 wards constituting a sequence. The study consists of ten 2-month periods with a phased introduction of the intervention. In the first period, all wards have a masked alert for 2 months. Afterwards the intervention (alert system) is implemented in a new sequence every 2-month period until the intervention is implemented in all sequences. The intervention includes the implementation of an electronic alert system developed in the hospital electronic medical records based on the quick sequential organ failure assessment (qSOFA). The alert system sends notifications of "possible sepsis alert" to the bedside nurse, charge nurse, and primary medical team and requires an acknowledgment in the health information system from the bedside nurse and physician. The calculated sample size is 65,250. The primary endpoint is in-hospital mortality by 90 days., Discussion: The trial started on October 1, 2019, and is expected to complete patient follow-up by the end of October 2021., Trial Registration: ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019., (© 2021. The Author(s).)

Sickle cell disease (SCD) is a genetic disorder, characterized by hemolytic anemia and vaso-occlusive crises (VOCs). Data on the global SCD impact on quality of life (QoL) from the patient viewpoint are limited. The international Sickle Cell World Assessment Survey (SWAY) aimed to provide insights into patient-reported impact of SCD on QoL. This cross-sectional survey of SCD patients enrolled by healthcare professionals and advocacy groups assessed disease impact on daily life, education and work, symptoms, treatment goals, and disease management. Opinions were captured using a Likert scale of 1-7 for some questions; 5-7 indicated "high severity/impact." Two thousand one hundred and forty five patients (mean age 24.7 years [standard deviation (SD) = 13.1], 39% ≤18 years, 52% female) were surveyed from 16 countries (six geographical regions). A substantial proportion of patients reported that SCD caused a high negative impact on emotions (60%) and school achievement (51%) and a reduction in work hours (53%). A mean of 5.3 VOCs (SD = 6.8) was reported over the 12 months prior to survey (median 3.0 [interquartile range 2.0-6.0]); 24% were managed at home and 76% required healthcare services. Other than VOCs, fatigue was the most commonly reported symptom in the month before survey (65%), graded "high severity" by 67% of patients. Depression and anxiety were reported by 39% and 38% of patients, respectively. The most common patient treatment goal was improving QoL (55%). Findings from SWAY reaffirm that SCD confers a significant burden on patients, epitomized by the high impact on patients' QoL and emotional wellbeing, and the high prevalence of self-reported VOCs and other symptoms., (© 2020 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background: There are a limited number of studies that address non-neutropenic fever episodes in children with cancer, and no standard approach exists., Method: We opt to retrospectively analyze the efficacy of the current clinical approach for management of non-neutropenic fever episodes and the associated risk factors among children with cancer at the Princess Noorah Oncology Center from May 2016 through December 2017., Results: A total of 480 non-neutropenic fever episodes were identified in 131 children, of which 62 episodes were triaged as high-risk non-neutropenic fever and 418 as low-risk non-neutropenic fever. Of those 480 non-neutropenic fever, 361 episodes (75.2%) were associated with the presence of central venous catheters. The overall failure rate of ceftriaxone mono-therapy was observed in 75.6% (11.7% in high-risk non-neutropenic fever with a mean C-reactive protein level of 21.1 (±23.2) mmol/L and 63.9% in low-risk non-neutropenic fever with a mean C-reactive protein level of 17.6 (±53.9) mmol/L). The overall bacteremia rate was 14.4%. The type of organisms isolated was mainly high-risk organisms in 59 non-neutropenic fever episodes (85.5%), OR 1.78 (95% CI: 0.45-7.04) p = 0.41. Of note, all bacteremia were associated with the presence of central venous catheter (100%). Of all the examined risk factors of outpatient treatment failure in low-risk non-neutropenic fever, only prolonged fever of more than three days were significantly associated with bacteremia OR 8.107 [95% CI: 1.744-37.691], p = 0.008. Noteworthy is that almost 43% of non-neutropenic fever episodes were associated with respiratory symptoms. This study provides a baseline for future prospective research assessing the pattern of non-neutropenic fever by focusing on associated risk factors.

Background: Travel burden has a substantial psychosocial impact and financial strain on childhood cancer patients and their families., Aims: To study the geographic distribution of childhood cancer and assess the travel burden for care in Saudi Arabia., Methods: This was a cross-sectional multi-institutional study that enrolled 1657 children with cancer who were diagnosed between 2011 and 2014. Cancer type/stage, city/region of residence, and city/region of treating centre were recorded. Travel burden was measured based on a 1-way distance in kilometres from the city centre to the treatment institution. This study was supported by Sanad Children's Cancer Support Association., Results: Diagnosis was leukaemia (45.2%), non-CNS solid tumours (30.2%), lymphoma (12.3%), CNS tumours (11.8%) and histiocytosis (0.5%). Childhood cancer centres were in the same city as where the patients lived in 652 (39.3%) cases, same region but different city in 308 (18.6%), different regions in 613 (37%), and not known in 84 (5.1%). The mean 1-way travel distance for patients who lived in different regions was 790 (range, 116-1542) km. A total of 536 (32%) patients lived ≥ 400 km and 216 (13%) > 1000 km from the treatment centre. Among 642 patients with acute lymphoblastic leukaemia who required 2-3 years of therapy, 197 (31%) lived ≥ 400 km and 94 (15%) >1000 km from the treatment centre., Conclusions: Nearly two thirds of patients with childhood cancer lived in different cities than the treatment centres, including one third of patients who lived ≥ 400 km away. There is a need to develop strategies to improve access to childhood cancer care., (Copyright © World Health Organization (WHO) 2020. Open Access. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Background: Delayed access to cancer care has been associated with childhood cancer death. Improving timely access to cancer care is the first important step in the cancer treatment journey. We introduced an electronic referral system (e-RS) to improve timely access to cancer care. This study aimed to assess the impact of implementing an e-RS on timely access to cancer care., Methods: A retrospective cross-sectional study of pediatric oncology patients selected through a consecutive nonprobability sampling technique was performed to determine the turnaround time (TAT) of children with cancer diagnosed 12 months before and after implementation of the e-RS. TAT was defined as time in hours from referral to approval for admission., Results: Of the 326 pediatric oncology patients diagnosed between January 2014 and December 2015, 59.9% were male and 40.1% were female. Median age for both sexes was 5.0 years (interquartile range [IQR]: 2.5-9.0 years). Among these, 98.2% were Saudi nationals. Hematological malignancies accounted for 50.6% of referrals and 16.6% had lymphoma. The median TAT of the manual referral system (m-RS) and e-RS was 18 h (IQR: 2-25 h) and 2 h (IQR: 1-16 h; P = .0001), median length of hospital stay during first admission was 11 days versus 9 days (P = .14), and death events occurred in 11 patients versus zero patients referred using the m-RS versus e-RS (P = .003), respectively., Conclusion: The introduction of an e-RS was associated with more rapid processing of pediatric patients for cancer treatment and fewer patient deaths during the initial evaluation and treatment during that time period., (© 2020 Wiley Periodicals, Inc.)

Many patients with sickle cell disease (SCD) need surgical management during their lifetime. The best approach for preoperative transfusion in SCD is still to be determined. In this single-center retrospective study, we included HBSS/HBS-Beta 0 -thalassemia patients younger than 16 years of age who underwent surgery between January 2008 and July 2019. Preoperative transfusion assignment (PTA) was based on SCD severity and surgical risk. Patients were assigned to no transfusion, simple transfusion, or exchange transfusion. A total of 284 patients were identified and 66 (23%) underwent 78 procedures. Mean age at the time of procedure was 8 (5-11) years, mean baseline hemoglobin was 8.5 (7.8-9.3) g/dl, and mean hemoglobin F was 18.4 ± 8.2%. SCD severity was low-risk in 57 (73%) and high-risk in 21 (27%) patients. Surgical risk was low-risk in 20 (25.6%) and medium-risk in 58 (74.4%) procedures. PTA was no transfusion in 17 (22%), simple transfusion in 40 (51%), and exchange transfusion in 21 (27%) procedures. Postoperative complications occurred in five (6.4%) of procedures only in the simple transfusion group (three acute chest syndrome, one hemolytic anemia, one pain crisis) undergoing medium-risk surgery. Preoperative risk-based transfusion assignment is feasible. Despite a high baseline hemoglobin level in the no transfusion group, none of the patients developed postoperative complications. It is possible that the high baseline hemoglobin F phenotype was protective and indicates the need to study the risk/benefit of interventions used in this phenotype.

Background: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated., Methods: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database., Results: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey., Conclusions: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease., (© 2020 American Cancer Society.)

Introduction: The incidence of childhood acute lymphoblastic leukemia (cALL) varies between countries likely as a result of competing risks including infections, access-to-care, socioeconomic influences, and/or ethnicity. However, little is known about disease burden in high-income Arab countries offering free-of-charge healthcare. The hypothesis was that, due to population characteristics (young age, high fertility and parental consanguinity rate), the incidence of cALL in Saudi Arabia is equal or higher than that observed in high-income Western countries., Methods: Saudi databases were used to calculate the incidence of cALL from 2001 to 2014. Incidence trends over time of children with ALL, 14-years of age or younger, were analyzed and compared with those reported in USA., Results: The age-adjusted incidence over the years was lower in Saudi Arabia compared to USA. However, the incidence trend of cALL in Saudi Arabia was increasing at a rate higher than that observed in USA (p < 0.001). The overall incidence of cALL in Saudi Arabia increased from 1.58/100,000 in 2001 to 2.35/100,000 population in 2014. The median annual increase was 4.58 %. The incidence in males increased from 1.88 to 2.71/100,000, and from 1.21 to 1.86/100,000 population in females., Conclusions: The reported incidence of cALL in Saudi Arabia is rapidly increasing. The increasing trend may reflect evolving socioeconomic structure, improved access-to-cancer care, and improved diagnosis/ reporting capacity. This highlights the need for better understanding of cALL causes and the need for the formation of separate national pediatric cancer registries in different countries to monitor childhood cancer incidence trends., Competing Interests: Declaration of Competing Interest The author declares that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The frequency of pathogenic/likely pathogenic (P/LP) germline mutations in cancer-related genes among children with cancer in highly consanguineous populations is not well studied., Methods: Whole-exome sequencing of germline DNA was performed in 60 children with acute leukemia. We used the St. Jude Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) data portal for the classification of germline variants by the St. Jude Medal Ceremony pipeline., Results: Fifty-seven patients had acute lymphoblastic leukemia (ALL) and three patients had acute myeloid leukemia. Parental consanguinity was present in 27 (45%) patients. All patients were of Arab ancestry. Three patients (5%) had a history of cancer in their siblings. Five patients (8.3%) had P/LP germline mutations in cancer-related genes. Three patients with B-ALL had heterozygous pathogenic mutations in TP53, BRCA1, and BRCA2; one patient with B-ALL had homozygous pathogenic mutation in PMS2; and one patient with T-ALL had LP homozygous mutation in AK2 that was associated with reticular dysgenesis. Among patients who had history of parental consanguinity, three (11%) had P/LP germline mutations compared with two (8%) in the absence of parental consanguinity. Fourteen (23%) patients had gold medal variants in cancer-related genes, 13 were heterozygous, and one was homozygous. Silver medal variants were present in 35 (58%) patients; all were heterozygous except one homozygous., Conclusions: Children with acute leukemia in Saudi Arabia had low frequency of P/LP mutations in cancer-related genes despite the high rate of consanguinity. Larger studies using whole-genome sequencing are needed to further explore the heritability of childhood leukemia., (© 2020 Wiley Periodicals, Inc.)

Purpose: Cancer treatment shortages are complex and a persistent problem worldwide. Patients with cancer are most vulnerable to drug shortages, which provides opportunities to examine the extent of the challenge(s) facing Saudi Arabia and to provide recommendations toward mitigating the impact of cancer treatment shortages on patient outcomes., Materials and Methods: A qualitative methodologic approach was conducted in April 2019 using a validated questionnaire and structured panel discussion for data generation., Results: Overall, 55 responses were received from practicing oncology health care professionals (26 pharmacists and 29 physicians). The annual average number of treated patients with cancer per institution was 640 (adults [n = 400] and pediatric [n = 240]). All respondents (100%) reported that cancer treatment shortages constitute a current problem in their center, with an average of 5 (range, 1-9) per month. The panelists recognized 2 fundamental points. First, the definition of cancer drug shortages should be standardized and recognized at the national level. Second, the current system must be improved to ensure proper and efficient use of the current resources. On that basis, the panelists developed 9 recommendations for action., Conclusion: Cancer drug shortage is a significant problem in all health centers in Saudi Arabia. This study presents challenges that should be addressed at the national level and essential consensus recommendations for a coordinated action developed by a panel of experts to tackle the current national problem of cancer treatment shortages. Implementing these recommendations will provide a blueprint for management of national drug shortages in general and cancer treatment shortages in particular.

Objectives: Acute lymphoblastic leukemia (ALL) with CNS2 status predicts inferior outcome and a high rate of CNS relapse, similar to overt CNS leukemia (CNS3). The purpose of this study was to determine if intrathecal (IT) dose intensification during induction would improve outcomes and reduce CNS relapse for CNS2 disease., Methods: From January 2001 to December 2014, children (1-14 years) with newly diagnosed ALL were treated at the Princess Noorah Oncology Centre (PNOC) following modifications of the Children's Oncology Group (COG) protocols. We intensified IT methotrexate (ITM) during induction for patients with CNS2 disease. Patients were evaluated for overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR)., Results: 449 children with T-cell (14.3%) or B-cell (85.7%) ALL were treated using PNOC-SR or PNOC-HR regimens (Jan 2001- Dec 2007) or CALL08 regimens (Arm A [SR], Arm B [IR], and Arm C [HR]) (Jan 2008 - Dec 2014). The 5-year OS, DFS, and CIR were 87.2 ± 1.6%, 81.7 ± 1.9%, and 13.0 ± 1.7%, respectively. The OS and DFS of patients with CNS2 were significantly superior to that of patients with CNS3 (P = 0.025 and P = 0.019, respectively). Patients with CNS2 had similar OS and DFS to those with CNS1. None of the patients with CNS2 at initial diagnosis experienced CNS relapse., Conclusions: ITM intensification during induction was associated with elimination of CNS recurrence in patients with CNS2 disease and childhood ALL. Controlled studies are needed to confirm this observation.

Background: Outcomes of relapsed/refractory childhood acute leukemia remain poor. We analyzed the safety/efficacy of fludarabine, cytarabine, and granulocyte colony stimulating factor, with/without idarubicin (FLAG ± IDA) as salvage therapy compared with recent published results of novel therapies., Methods: This retrospective study included children aged 1 to 15 years with relapsed/refractory acute leukemia who received FLAG ± IDA salvage therapy from January 2000 to December 2014. Patients with infant leukemia, mixed lineage leukemia, Philadelphia-positive acute leukemia, or secondary leukemia were excluded., Result: Fifty patients were identified: 25 with acute lymphoblastic leukemia and 25 with acute myeloid leukemia. The median age at initiation of FLAG ± IDA was seven years. Site of relapse was the bone marrow in 29, isolated central nervous system in 11, and combined in 10 patients. FLAG ± IDA was used after first relapse in 68% and after multiple relapses in 32%. Complete remission was achieved in 34 (68%) patients. No variables predictive of complete remission were identified. Grade 3 or greater toxicity was observed in 96% and 6% died from toxicity. Toxicities included hematologic toxicity (96%), infection (52%), and enterocolitis (28%). Twenty-four of 50 (48%) patients achieved a sustained complete remission and survived to bone marrow transplantation. The five-year overall survival was 23.9% ± 6.9%. Patients achieving second complete remission and patients proceeding to bone marrow transplantation following second complete remission demonstrated significantly improved overall survival (p = 0.001)., Conclusion: Despite a 68% complete remission rate using FLAG ± IDA, only 48% of patients survived to bone marrow transplantation. The regimen was associated with 96% toxicity and only one in four patients was alive at five years. This underscores the need to find more effective lower toxicity salvage regimens.

Introduction: The development of cancer programs in developing countries to meet the standards observed in high-income developed countries is not well documented., Methods: An analysis of patient care of children with acute lymphoblastic leukemia (ALL) at the Princess Noorah Oncology Center over 25 years was performed. A number of improvements were introduced over time including optimizing the cancer care delivery culture, improving access to care, optimizing supportive care, and refining diagnostic and therapeutic capabilities. Outcomes were evaluated over three time periods (period 1, 1989-2000; period 2, 2001-2007; and period 3, 2008-2014). These findings were compared with results of collaborative clinical trials (CCT)., Results: Of the 686 patients treated, the five-year overall survival (OS) rate improved from 74% ± 2.7% in period 1 to 89.5% ± 2.3% in period 3 (P < 0.0001). Among all patients, the five-year cumulative incidence of death decreased from 26% in period 1 to 10.5% in period 3 (P < 0.0001). This decrease was mainly due to reduction in the incidence of death from disease (P < 0.00001). In contrast, significant improvement in T-cell ALL survival outcomes (P < 0.0001) was observed overtime (from period 1 to period 3) as a result of significant reduction in both toxic deaths (P = 0.005) and disease-related deaths (P = 0.001)., Conclusions: Survival outcomes in Saudi Arabia have improved with five-year OS rate now approaching 90%. However, further population-based research is needed to understand variance in outcomes from those reported by CCT groups., (© 2019 Wiley Periodicals, Inc.)

Background: The outcome of childhood acute myeloid leukemia (AML) in first relapse (rAML) remains poor. Reported overall survival (OS) rates vary between high-income developed countries and those with fewer resources. The OS of rAML in high-income developing countries (HIDCs) has not been reported., Patients and Materials: A multicenter study was performed in an HIDC. The outcome of patients with relapsed non-M3/non-Down syndrome AML was evaluated. Three-year OS was computed using the Kaplan-Meier method, and predictors of OS were analyzed using a Cox proportional hazards model., Results: A total of 88 patients with non-M3/non-Down syndrome AML diagnosed between January 2005 and December 2012 with a first relapse were identified. Their 3-year OS was 22.6% ± 5.4%. Patients with inv(16) and t(8;21) had an OS of 75.0% ± 21.7% and 36.0% ± 16.1%, respectively. Worse outcomes were associated with "other intermediate" and 11q23 rearrangement AML (OS of 9.4% ± 8.7% and 10.7% ± 9.6%, respectively). Patients experiencing time to relapse (TTR) less than 1 year had shorter OS than those with a longer TTR (14.6% ± 5.4% vs. 41.1% ± 11.5%; P = .006). The outcome of patients after stem cell transplantation (SCT) in second complete remission (CR2) was superior compared with no SCT (50.9% ± 11.2% vs. 7.7% ± 4.6%; P = .001). TTR, risk group, CR2, and SCT in CR2 were the most significant predictors for survival., Conclusions: rAML remains a clinical challenge. Genetic variability in outcomes was observed. A majority of patients with inv(16) were successfully salvaged post-relapse, whereas patients with 11q23 rearrangement had a poor prognosis. Only one-third of those with t(8;21) rAML survived. Better access to SCT in HIDCs is needed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Refinement of risk-based treatment stratification by minimal residual disease (MRD) at different time points has improved outcomes of childhood acute lymphoblastic leukemia (ALL). In this prospective study we evaluated effects of such stratification, including intensification of therapy based on response assessment at day-15 and MRD at day-29 of induction to test if treatment intensification would improve outcomes., Methods: 241 patients, 1-14 years old, newly diagnosed with ALL, were recruited and stratified by risk and MRD response into three treatment Arms (A, B, or C). Arm A was modified from COG AALL0331, B from AALL0232, and C from AALL0232 and AALL0434. Assignments were according to NCI risk, phenotype, rapid vs. slow early response (SER), steroid pretreatment, MLL rearrangement ( MLLR ), CNS3, and testicular involvement. Patients on Arm A had treatment intensified early based on day-15 marrow results or late based on end-of-induction MRD., Results: 5-year OS, EFS, and CIR were 89.5% ± 4.0%, 87.6% ± 4.3%, and 7.1% ± 3.5%. No significant difference was found by B- vs. T cell phenotype. 5-year OS, EFS, and CIR for B-cell ALL were 90.5% ± 2.4%, 88.7% ± 2.6%, and 6.4% ± 2.0%. Outcomes for patients with t (1;19)/ TCF3 - PBX1 and MLLR were significantly (p ≤ 0.05) worse than for other patients. MRD level at end-of-induction associated with outcomes, but association with a specific MRD value at end-of-induction varied significantly by NCI-risk group. Late treatment intensification based on end-of-induction MRD significantly improved survival outcomes for NCI-SR patients, however, patients with NCI-HR and positive MRD at end-of-induction had significantly inferior outcomes despite intensification. MRD transitions between day-15 and day-29 of induction associated with differences for OS and EFS., Conclusions: Arm switching to a more intensive protocol had mixed results. Assigning patients by end-of-induction MRD-risk alone did not reflect response kinetics of the different NCI-risk groups. Although late treatment intensification improved outcomes of NCI-SR patients with positive MRD at end-of-induction, further refinement is needed to improve outcomes of NCI-HR with SER. Integration of NCI-risk group with specific MRD value and time point allows more refined treatment stratification. Trial Registration Protocols were approved by King Abdullah International Medical Research Center and Ethics Review Committee RC08053J.

Sixty-three children (1-14 years of age) newly diagnosed with T-cell acute lymphoblastic leukemia were treated from January 2001 to December 2014. Patient outcomes were evaluated based on the regimen received; Capizzi methotrexate (C-MTX) vs. high-dose methotrexate (HDMTX). Complete remission (CR) was achieved in 54 of 60 (90.0%) patients and 3 patients died during induction. The 5-year overall survival (OS) and disease-free survival (DFS) were 88.3 ± 6.5% and 85 ± 7.5%, respectively. Post-induction, 35 patients were treated with HDMTX and 25 with C-MTX. There was no difference in OS or DFS for patients treated with HDMTX vs. C-MTX ( P  > 0.05 for both). Central nervous system involvement (CNS3) was associated with inferior survival outcomes compared to Non-CNS3 patients (OS, CNS3 73.3 ± 9.1% vs.non-CNS3 93.2 ± 2.6%, (P = 0.045) and DFS, CNS3 66.7 ± 10.4% vs. non-CNS3 90.9 ± 3.1% ( P  = 0.0163)). Delayed radiation in CNS3 was associated with relapse ( P  = 0.0037) regardless of regimen. Thus optimization of CNS-directed therapy for patients with CNS3 is needed.

Background & Aim: Hereditary cancer susceptibility syndromes (HCSS) are reported in up to one-third of children with cancer. Diagnosis of HCSS is crucial for implementation of surveillance protocols. We identified children who fulfilled criteria for HCSS in Saudi Arabia using the American College of Medical Genetics and Genomics (ACMG) guidelines, addressing the utility of these guidelines in a highly consanguineous population., Methods: This multi-center cross-sectional study recruited 1858 children with cancer between January 2011 and December 2014. HCSS criteria were based on the ACMG guidelines., Results: Seven hundred and four (40.4%) out of 1742 eligible patients fulfilled criteria for HCSS. Consanguinity was reported in 629 (38%) patients, with 50 (2.9%) first-degree, 535 (30.7%) second-degree, and 272 (15.6%) third-degree relatives affected with cancer. Two hundred and eighty eight (17.4%) leukemia and 87 (5.3%) brain tumour patients fulfilled HCSS criteria, with parental consanguinity being the most frequent criterion in both (leukemia 85.4%, brain tumors 83.9%). However, leukemia was less frequent in patients of consanguineous parents (p = 0.023)., Conclusion: Four out of 10 children with cancer fulfilled criteria for HCSS, most often due to consanguinity. This higher than expected prevalence suggests the need to validate consanguinity as a criterion for HCSS in highly consanguineous populations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival., Method: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia. Patients were treated based on the standard protocol used by the center following the PETHEMA or the C9710 treatment protocols. We modeled 5-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) vs. treatment and potential covariates of age at diagnosis, involvement of central nervous system (CNS), and white blood cell (WBC) levels., Results: The median age was 10.4 years with a male:female ratio of 1.9. WBC was 10 × 10 9 /l or greater in 57% and CNS involvement was confirmed in 13%. OS, EFS, and CIR were 74 ± 12%, 55 ± 19%, and, 36 ± 17% respectively. No significant difference was found by treatment protocol. WBC levels were significantly prognostic for all negative events, but treatment with C9710 significantly ameliorated negative WBC effects. Overall outcomes were comparable to those reported in developed countries., Conclusions: Access to modern care is likely to be a critical factor in successful and comparable outcomes of childhood APL across the globe. In the present study, utilizing a cytarabine-containing protocol improved outcome of high-risk pediatric patients with APL.

Background: Treatment modality impacts outcome of childhood low-grade glioma (LGG). Optimizing management in developing countries can be challenging. This study evaluates the clinical characteristics, treatment, and factors influencing outcome of childhood LGG in Saudi Arabia., Patients and Methods: This study retrospectively evaluated 59 children consecutively diagnosed with LGG between January 2001 and June 2016., Results: Median age at diagnosis was 6.0 years. Pilocytic astrocytoma represented 64.9% of cases. The anatomic site was cerebellar in 23.7%, cerebral in 18.6%, hypothalamic-optic pathway in 33.9%, and midline in 23.7%. The 5-year overall survival (OS) and progression-free survival (PFS) were 90.6 ± 4.7 and 54.3 ± 8.4%, respectively. Initial treatment was observation in 28.8%, surgery alone in 35.6%, chemotherapy in 13.6%, radiotherapy in 5.1%, and combined in 16.9% of cases. The corresponding 5-year PFS was 56.3 ± 15.6, 53.3 ± 14.0, 22.9 ± 19.7, 33.3 ± 27.2, and 88.9 ± 10.5%, respectively (p = 0.006). Among the 61% who had surgical intervention (either alone or in combination with other therapies), 22% achieved complete resection with 5-year radiation/progression-free survival (RPFS) of 87.5 ± 11.7% compared to 27.6 ± 10.8% for subtotal resection/biopsy and 62.2 ± 17.0% for no surgery (p = 0.013). Adjuvant therapy for residual tumor improved survival with 5-year PFS of 66.7 ± 19.2% for chemotherapy and 100% for radiotherapy compared to 12.5 ± 11.4% for observation (p = 0.033)., Conclusions: We identified variability in the outcomes of LGG. Fewer surgeries with lower rates of total resection were noted, compared to reports from international cooperative groups. The extent of resection was predictive of RPFS. Adjuvant therapy improved the outcome of patients with residual disease, resulting in PFS rates comparable to international data.

This report presents a case of Bloom syndrome (BS) in a consanguineous Saudi family. The patient, an 11-year-old male with mature B-cell lymphoma, had minimal therapeutic response and significant dose-limiting toxicity with standard chemotherapy treatment. He later responded successfully to a rituximab-based chemotherapy protocol. This case highlights that the rituximab-based chemotherapy protocol is an effective and safe treatment alternative for mature B-cell lymphoma in patients with BS. Further trials are warranted to investigate this modality of treatment., (© 2016 Wiley Periodicals, Inc.)