The Characteristics and Follow-Up of SARS-CoV-2 Infection in Pediatric Oncology Patients.

Introduction Clinical data about the first and second most prominent waves of SARS-CoV-2 among pediatric cancer patients were inconsistent. This study aims to retrospectively report the clinical characteristics and outcomes of SARS-CoV-2 infection in pediatric oncology patients. Methods This is an observational, retrospective study conducted in a tertiary care oncology center from March 2020 to May 2022. We reviewed the prevalence, severity of symptoms, and duration of positivity in relation to blood count laboratory data and mortality with a follow-up of 30 days post-infection for SARS-CoV-2. Results A total of 396 PCR tests were performed on 342 pediatric cancer patients. The overall rate of SARS-CoV-2 positivity was 43.1% (2.7% in the first wave and 95.4% in the second wave). Among 342 screened pediatric cancer patients, 72 patients had confirmed SARS-CoV-2 positivity in 92 different episodes. Nearly 59% had a mild or moderate infection, with fever and cough as the predominant presentations. The mean duration of positivity was 18.4±7.76 days. Comparing the laboratory values before and after acquiring the COVID-19 infection, only monocytes, hemoglobin, hematocrit, and platelets were statistically significantly affected, with P-values of 0.002, 0.03, 0.02, and 0.01, respectively. More than 18% of patients had grade 3 to 4 neutropenia (absolute neutrophil count=0.39±0.35) before COVID-19 infection and remained neutropenic throughout the disease, regardless of symptom severity. The mean recovery time was 13.67±8 days, which resulted in a delay in cancer treatment delivery of up to four weeks in 42.2% of patients. Conclusion Our data demonstrated that pediatric cancer patients with SARS-CoV-2 infection have a mild to moderate course of COVID-19 disease, with the majority being symptomatic, yet a great portion of our study population experienced treatment interruptions reaching up to four weeks caused by COVID-19.

A Retrospective Single-Center Study of Sevelamer Hydrochloride for the Treatment of Hyperphosphatemia in Children With Tumor Lysis Syndrome.

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.

Evaluation of handling, storage, and disposal practices of oral anticancer medications among cancer patients and their caregivers at home setting in the Princess Noorah Oncology Center.

BACKGROUD: Oral medications are commonly prescribed for many cancer patients. Unfortunately, most of them are dispensed without proper counseling about handling practices. We aimed to evaluate the handling, storage, and disposal practices of oral anticancer medications among cancer patients and their caregivers at home. METHODS: A cross-sectional questionnaire was filled in by adult cancer patients or caregivers who received oral anticancers and/or visited an outpatient pharmacy over two months. RESULTS: A total of 201 participants were interviewed, 67% were female, and nearly 44% were between 40 and 60 years of age. The majority of participants were educated (78%). The top five medications involved were: tamoxifen, capecitabine, letrozole, dasatinib, and imatinib. More than 95% of participants reported that medications were kept away from children and pets in the original container and stored away from extreme heat, cold, and humidity. Hand washing and wearing gloves were not consistently practiced. Only 5% reported "Always" wearing gloves, while 24% reported "Always" washing hands after handling anticancer medications. The participants reported that they had been informed about safe handling and storage by their physician (39%) and pharmacist (25%), while 34% had not been informed. In terms of disposal practices, 66% of patients have not had any unused or expired medications, 29% disposed them in the trash, and 27% returned them. CONCLUSIONS: Our findings suggest that patients and caregivers' handling practices of oral anticancer medications are inconsistent with the published recommendations. Hence, appropriate and comprehensive education is needed to mitigate the risk of exposure to these agents in the home setting.

Coping with the residency program during COVID-19: Hematology oncology pharmacy residents' perspective.

INTRODUCTION: The COVID-19 pandemic has led to significant changes in all governmental activities in Saudi Arabia including training and teaching, with the majority of such activities suspended in response to the COVID-19 pandemic. We aim to share the challenges that Hematology Oncology Pharmacy (HOP) residents faced during the quarantine period and provide recommendations on how to cope with the residency journey. METHOD: We followed a qualitative methodological approach in March 2020 using a structured virtual group discussion for data generation. RESULTS: All six PGY2 hematology oncology pharmacy (HOP) residents were included in the group discussion. The group agreed that the need for HOP services during this pandemic is beyond the scope of oncology pharmacists' normal daily practice. The group recognized two fundamental points. First, the goal of the current training should be customized to the most pressing need and recognized at the national level. Second, the current training system should be improved to ensure efficient use of current resources. On this basis, the group developed six main recommendations for action. CONCLUSION: The current situation is a challenge for all healthcare providers, and the majority of the nation's current generation never dealt with such a situation in days gone by. This paper presents the challenges that should be addressed at the national level and provide a fundamental consensus recommendation for practical approaches to maximize learning and minimize disruption to trainees' progression while maintaining patient-pharmacy quality of care.

Addressing Cancer Treatment Shortages in Saudi Arabia: Results of a National Survey and Expert Panel Recommendations.

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.

Impact of the e-prescribing system on the incidence and nature of drug-related problems in children in a Saudi hospital.

OBJECTIVES: To determine the impact of a computerised physician order entry (CPOE) system on the drug-related problems' (DRPs) incidence and characteristics in hospitalised children in a Saudi hospital, and to compare DRPs incidence pre-/post-CPOE implementation. METHODS: An observational study. DRPs were identified by pharmacists, reviewing children's (0-14 years) medical records on CPOE system, in paediatric wards and/or attending emergency department. DRPs preventability and severity were assessed. RESULTS: A total of 657 paediatric patients were included, with 235 (35.8%) experienced 328 DRPs, majority were preventable (99.7%, 327). Difference in DRP incidence pre- and post-CPOE implementation (44.8% versus 35.8%, P < 0.01) was significant. CONCLUSION: The CPOE system has significantly reduced DRPs incidence in children in the study hospital.

Intrathecal dose intensification by CNS status at diagnosis in the treatment of children with acute lymphoblastic leukemia.

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.

FLAG/FLAG-IDA regimen for children with relapsed/refractory acute leukemia in the era of targeted novel therapies.

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.

Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia.

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.

High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia.

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 ±â€¯6.5% and 85 ±â€¯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 ±â€¯9.1% vs.non-CNS3 93.2 ±â€¯2.6%, (P = 0.045) and DFS, CNS3 66.7 ±â€¯10.4% vs. non-CNS3 90.9 ±â€¯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.