The effects of thymic epithelial monolayer-conditioned medium on suppressor cell function following chemotherapy in pediatric patients.

Background: Cancer is a highly debilitating non-communicable disease and an essential contributor to the global burden of disease. Pediatric patients are highly exposed to multiple drugs for the management of cancer. Monitoring drug utilization patterns helps to provide feedback to healthcare providers to ensure the rational use of medicines; as a result, it increases the therapeutic efficacy and decreases the frequency and severity of adverse drug reactions (ADRs). Therefore, this study assessed the utilization pattern and ADRs of chemotherapy in pediatric patients at Muhimbili National Hospital (MNH). Methods: A descriptive cross-sectional study was conducted for three months from February to April 2021 in pediatric cancer patients undergoing chemotherapy at MNH. A total of 123 children diagnosed with cancer and on chemotherapy were enrolled in this study. Patients' socio-demographics, clinical information, chemotherapy status, prescribed medications, and prevalence of ADRs were collected. Descriptive statistics was used in data analysis, whereby frequency and proportions were used to summarize data. Results: Out of 123 patients, 62.6% were male. Most patients received an average of four anticancer drugs. Vincristine (55.3%) was the most used anticancer drug, followed by cytarabine (44.7%) and methotrexate (42.3%). The most used adjuvant drugs were ondansetron (30.9%), hydrocortisone (27.6%), and piperacillin/tazobactam (23.6%). The percentage of drugs prescribed from the Tanzania Essential Medicine List (TEML) and World Health Organization (WHO) list was 66.4% and 93%. Most (87%) of the patients reported having experienced ADRs whereby nausea and vomiting (45.8%), hair loss (33.6%), and neutropenia (32.7%) were more prevalent ADRs reported. Conclusions: This study found the drug prescribing pattern to be in line with the essential medicine list, but the average number of drugs prescribed was higher than recommended. ADRs were prevalent among pediatric cancer patients.

FAILURE OF CONCONAVALIN A-STIMULATED LYMPHOCYTES TO SUPPRESS RESPONSIVENESS TO PHA AND ALLOGENEIC CELLS AS A MARKER OF DISORDERED IMMUNOREGULATION

<p>Supplementary Table1.Characteristic of antibodies used in the flow cytometry evaluation.Supplementary Table2.Primer sequence and product size for PCR amplification.Supplementary Table3.Clinical and baseline clinical characteristics of OC patients with diabetes</p>

<p>Supplementary Fig.1.Increased MDSCs levels in peripheral blood and tumor from OC patients.Supplementary Fig.2.Characterization of phenotype and immunosuppressive activity of MDSCs in OC patients.Supplementary Fig.3.Phenotypic analysis of MDSCs following metformin treatment.</p>

ABSTRACTIntroduction: Advancing appropriate and adequate analgesic pharmacotherapy in pediatric patients with cancer is an area of clinical need. Few studies have been performed to evaluate the selection of an analgesic and appropriate dosing corresponding to analgesic effect among pediatric cancer patients. This review describes information related to pharmacokinetic, pharmacodynamic, and pharmacogenomic (when applicable) considerations for analgesics that are commonly used to manage pain experienced by pediatric patients with cancer.Areas covered: Analgesics commonly used to treat pediatric patients with malignancy patterned after the World Health Organization’s ‘analgesic ladder’ for cancer pain management.Expert opinion: Addressing pain management safely and effectively in pediatric patients with cancer will require advances in both drug development, to increase the armament of analgesics available for children, and our pharmacologic understanding of those analgesics in current use. However, performing the necessary types of studies to develop new analgesics, or gain knowledge of existing therapy, within a population that is relatively small, diverse, and who experience pain originating from a variety of sources, is a tremendous challenge.

Background and objectiveAssessing the impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life (QoL) of cancer patients is critical. However, there is a dearth of specialized assessment tools designed specifically for pediatric cancer patients. The aim of this study was to develop and validate the Pediatrics Functional Living Index-Emesis (PFLIE) as a patient-reported outcome measure (PROM) to assess the impact of CINV on QoL in pediatric patients. This study was approved by the Institutional Review Board of Sun Yat-sen University Cancer Center (Approval No. B2021-113-01) and was conducted in accordance with the Declaration of Helsinki.​Materials and methodsThe reliability, content validity, structural validity, and concurrent validity of the PFLIE were assessed through two rounds of Delphi expert consultation and a questionnaire survey of 90 pediatric cancer patients receiving chemotherapy at a tertiary care hospital cancer center in China.ResultsThe PFLIE consists of two domains: nausea (10 items) and vomiting (10 items). The content validity index (CVI) for both the nausea and vomiting domains was 0.933. The Cronbach’s alpha coefficients for the total scale, nausea domain, and vomiting domain were 0.964, 0.928, and 0.943, respectively. Item-domain correlations were stronger for the PFLIE (r = 0.678-0.882) across domains compared to across-domain correlations (r = 0.493-0.780), suggesting that the PFLIE has acceptable construct validity. In addition, the PFLIE demonstrated acceptable concurrent validity.ConclusionsThe validity and reliability of the Chinese version of the PFLIE are reliable and valid. The tool can help healthcare providers effectively identify and manage CINV symptoms, thereby improving the QoL of pediatric cancer patients. In low- and middle-income countries (LMICs) with limited resources, PFLIE can be used to improve the management of CINV and to ensure that pediatric cancer patients receive adequate care despite inadequate healthcare infrastructures. The tool can be used to improve the management of CINV and to ensure that pediatric cancer patients receive adequate care despite inadequate healthcare infrastructures.​

Background RSV vaccine was recently introduced, and is recommended for infants and immunosuppressed children. Viral respiratory infections may pose a significant risk for pediatric cancer patients and lead to delay in chemotherapy, prolonged illness, hospitalization, and mortality. Limited data exist on predictive factors for adverse clinical outcomes. This study aims to describe associations between the existence of RSV and severe outcomes among children with hematologic cancer. Methods A retrospective cohort study among pediatric cancer patients treated in the Pediatric Hematology-Oncology Department at Rambam Health Care Campus from 2016 to 2022. Patients with a positive rt-PCR test for one of the following viruses: Respiratory Syncytial Virus (RSV), Adenovirus, Human Metapneumovirus (HMPV), SARS-CoV-2, Parainfluenza, or Influenza were included. Demographic, clinical, and laboratory data were collected for each case. Logistic regression was conducted to assess the association between independent variables and severe outcomes (admission to pediatric intensive care unit, hospitalization above seven days, co-bacterial infections, and 30 days mortality). Results A total of 366 viral infections episodes were identified among 238 patients, with a median age at presentation of 5.15 years. Hematological malignancies were diagnosed in 187 patients (51%), solid tumors in 113 patients (31%), and 66 patients (18%) had undergone bone marrow transplantation. There were 65 events of RSV (18%). A total of 38 severe events was recorded. One patient died within 30 days of infection with RSV. Among the subgroup of hematological malignancies, RSV was positively associated with severe outcomes (OR = 4.08, p = 0.048), adjusted for demographic and clinical variables. Conclusions This study identifies RSV infection in association with severe outcomes among hematological pediatric cancer patients. This emphasizes the importance of RSV vaccination in immunocompromised pediatric patients. Key messages • RSV among hemato-oncology pediatric patients is a strong risk factor for severe outcomes. • Complying with the RSV vaccine recommendations for immunosuppressed children is of a major importance.

10029 Background: The association between family history of cancer (FHC) and outcome remains uncertain. Relapse and survival of children with FHC has not been well studied. Such information would be valuable for prognosis, refining treatment protocols, and long-term follow-up in pediatric patients with FHC. Methods: An historical cohort study of all pediatric patients diagnosed with cancer at Lucile Packard Children's Hospital at Stanford from 1999 - 2002 was performed (n = 363, mean age: 8.4 yrs [0–28 yrs]). FHC among 1st, 2nd and 3rd degree relatives was obtained from the first 10 consecutive encounters in the electronic medical record. Relapse, secondary malignancy, and survival data were also acquired. The relative risks for these endpoints were calculated between patients with FHC among 1st and/or 2nd degree relatives and those with negative FHC. Patients without documented FHC were excluded (n = 100). Results: 108 (41%) newly diagnosed pediatric patients had reported FHC (1st Degree: n = 14 [5%], 2nd Degree: n = 58 [22%], 3rd Degree: n = 36 [14%]). Patients with reported FHC among 1st and/or 2nd degree relatives were at increased relative risk [RR] for relapse (1.96, 95% confidence interval [CI] 1.27–3.02) compared to patients with negative FHC (n = 191). In particular, patients with Hodgkin Disease (HD) and FHC (n = 12) were more likely to relapse (RR 1.79, 95% CI 1.19–2.72) and at increased risk of death (RR 1.72, 95% CI 1.18–2.53), compared to HD with negative FHC (n = 8). Similarly, patients diagnosed with ALL and FHC (n = 22) had increased risk of death (RR 2.25, 95% CI 1.06–4.8) compared to ALL patients with negative FHC (n = 56). For patients diagnosed with any pediatric cancer and positive FHC in 1st degree relative, RR of death was significantly elevated (3.74, 95% CI 1.20–11.70). Conclusions: Pediatric cancer patients with positive FHC among 1st and/or 2nd degree relatives appear to have higher relative risk of relapse compared to those with negative FHC. Additionally, an increased risk of death was associated with HD and ALL patients with positive FHC. Patients with 1st degree relative with malignancy had an increased risk for death compared to those without cancer among 1st degree relatives. These findings may reflect underlying genetic predispositions in children which contribute to outcome. No significant financial relationships to disclose.

Pediatric cancer treatment includes several chemotherapeutic drugs in combination with adequate supportive management. Symptom distress among pediatric cancer patients on chemotherapy interferes with treatment compliance. Poorly managed distress leads to the decline of the child’s ability physically and mentally and deteriorates the quality of life. This paper shows the effect of chemotherapeutic drugs induced symptom distress, and the effect of early diagnosis in the management and improvement in the quality of life of pediatric cancer patients. For this study60, pediatric cancer patients aged between 10 to 18 years including both the gender were chosen using purposive sampling. Using the M.D. Anderson symptom inventory the symptom distress experienced by the pediatric cancer patients was assessed. The present quantitative cross-sectional study was conducted at the AIIMS, Raipur. The data were analyzed using the descriptive Statistical Package for Social Science Version 16 (SPSS 16). The categorical data was analyzed using chi –square test and the cut off p-value at ≤0.05. Among, the pediatric cancer patients 77.65% (SD 18.85) were experiencing severe symptom distress when on chemotherapy. Whereas 53.65 %( SD 9.63). of them experiencing the symptoms those disturb their activities of daily living in the last twenty four hours at p-value of ≤0.05. There is a need for an adequate support system from the school, social relationship, siblings, and health care team for improving the quality of life of pediatric cancer patients. Animal facilitated therapy, artistics expressions, medical play, procedural education, well organized home bound or school programs help the pediatric cancer patients to manage the symptom distress, thereby improving the treatment outcome. The specific supportive chemotherapeutic management is essential for the pediatric cancer patient’s treatment compliance and prognosis. The health care team, especially nurses play a vital role in early detection of chemotherapeutic agents induced symptom distress and its management.

Background:Many studies have tried to be establish a pathogenic role for human herpesvirus-6 and -8 (HHV-6, HHV-8) in malignant diseases, but whether these viruses plays a role in these pathologies remains unclear. HHV-6 and HHV-8 seropositivity were shown in a healthy population. There is no published data in Turkey about seroprevalence of these viruses. We aimed to determine the seroprevalence of HHV-6 and HHV-8 in pediatric cancer patients and to compare with healthy Turkish children's viral seroprevalence.Patients and Methods:Ninety-three pediatric cancer patients and 43 age-matched healthy children were included in the study. All sera were screened for antibodies to HHV-6 and HHV-8 by ELISA.Results:HHV-8 immunoglobulin G (IgG) was positive in 3.3% of lymphoma patients, in 4.8% of acute lymphoblastic leukemia (ALL) patients, in 4.8% of retinoblastoma patients and in 7% of healthy children. There was no significant difference in HHV-8 seroprevelance between these groups. HHV-6 seroprevalence was 81% in ALL patients, 70% in lymphoma group, 81% in retinoblastoma patients and 69.8% in healthy children. Although there was no significant difference in HHV-6 prevalence between healthy children and pediatric cancer patients, HHV-6 seropositivity tended to be higher in retinoblastoma patients under age of 4 years (odds ratio: 2.925).Conclusion:HHV-6 seroprevalence was higher than HHV-8 seropositivity in our study. Viral studies related HHV-6 seroprevelance in retinoblastoma patients would be useful to clarify if there is any etiological association between HHV-6 and retinoblastoma.

Internalized stigma adversely impacts childhood cancer survivors, limiting their ability to reintegrate with their communities and maintain social networks. However, the impact of internalized stigma on children undergoing cancer treatment is unknown, and no interventions exist to mitigate it. The Activating Events-Beliefs-Consequences (ABC) model from Cognitive Behavioral Theory (CBT) has been used to analyze internalized stigma and inform interventional work. This study employs the ABC model as a conceptual framework to explore how internalized stigma manifests for children recently diagnosed with osteosarcoma and retinoblastoma in Guatemala, Jordan, and Zimbabwe. We conducted semi-structured interviews with nine adolescent patients (aged 12-18), 28 caregivers, and 19 clinicians at tertiary cancer centers in Guatemala, Jordan, and Zimbabwe. Interviews occurred in Spanish, Arabic, Shona, and English and were transcribed and translated into English for analysis. Two coders independently coded transcripts, resolving disagreements through consensus and third-party adjudication. A framework analysis used the ABC model to understand manifestations of internalized stigma, defined a priori as "a patient's own adoption of negative societal beliefs or feelings, including changes in self-identification." Patients, caregivers, and clinicians all described internalized stigma in pediatric cancer patients. Cancer-related physical changes and community stigma activated internalized stigma. Patients responded to these events by forming beliefs about their appearance, abilities, normalcy, and future, which shaped their behaviors and emotions. While some patients internalized stigmatizing beliefs about themselves and experienced negative consequences, others maintained resilient self-beliefs that fostered adaptive behaviors and emotions. Knowledge about the disease, supportive interactions with survivors and other patients, and caregiver support promoted stigma resilience. Our results demonstrate that internalized stigma impacts pediatric cancer patients from the time of diagnosis, highlighting the relevance of the ABC model in understanding this complex phenomenon. Our findings suggest CBT-based interventions that target patient beliefs, address identified activating events, and enhance multilevel support could help mitigate internalized stigma in pediatric cancer patients. Additional research should explore the efficacy of such interventions, the transferability of our findings to children with other cancer diagnoses and to various geographies, as well as how internalized stigma evolves across the cancer continuum.

Comparison of Heparin and Saline for Prevention of Central Venous Catheter Occlusion in Pediatric Oncology: A Systematic Review and Meta-Analysis

Retinoblastoma is a childhood malignancy of the retina. To increase the exposures of systemic chemotherapy, high-dose cyclosporine, as a P-glycoprotein modulating agent, has been combined with a standard chemotherapy. However, the effective and safe dose of cyclosporine has not been well evaluated. This study is to optimize cyclosporine dose using population pharmacokinetic modeling. Clinical data were obtained from 161 systemic chemotherapy cycles of 34 pediatric retinoblastoma patients between December 2006 and April 2015. Total 15 scenarios were simulated by 5 different doses (12, 14, 15, 17, and 20 mg/kg) of cyclosporine in 3 different weight groups (5-10, 10-15, and 15-20 kg). Numerical success ratio was obtained after assessing the simulated target cyclosporine concentration in the range of 2,000-2,500 ng/mL using NONMEM version 7.3 software. A final model was built based on a 1-compartment model with weight-normalized allometric scaling to minimize the variability of pediatric size. In simulations, numeric success ratio with 15 mg/kg/day and the above were higher than that of traditional doses in all of the scenario groups. No significant adverse responses were reported. Conclusion and Relevance: High-dose cyclosporine regimen as a P-gp modulator is required to improve the efficacy of systemic chemotherapy with caution in pediatric patients with retinoblastoma. Clearance, volume of distribution, and body weight are important parameters to consider in selecting adequate dosing regimen.

Obesity correlates with adverse events (AEs) in children with acute myelogenous leukemia and during maintenance therapy for acute lymphoblastic leukemia (ALL). Less is known about AEs in obese ALL patients during pre-maintenance chemotherapy. We evaluated the relationship between obesity (body mass index (BMI) ≥ 95th percentile) and AEs during pre-maintenance chemotherapy in pediatric patients with ALL. One hundred fifty-five pediatric ALL patients diagnosed at a single institution between 2006 and 2012 were retrospectively evaluated for infections, treatment-requiring hypertension, insulin-requiring hyperglycemia, pancreatitis, pediatric intensive care unit admissions, sepsis, febrile neutropenia (FN) admissions, thrombosis, hepatotoxicity, and nephrotoxicity. Univariate and multivariable analyses compared proportions of obese versus nonobese patients experiencing AEs. AEs occurring significantly more frequently in obese patients by univariate analysis included treatment-requiring hypertension (17.5% vs 6.1%; OR, 3.27; 95% CI, 1.1-10.0, P=0.0497) and insulin-requiring hyperglycemia (25.0% vs 11.3%; OR, 2.62; 95% CI, 1.04-6.56, P=0.04). Obese patients had greater incidence rates for recurrent admission-requiring infections (incidence rate ratio (IRR) 1.64; 95% CI, 1.08-2.48, P=0.02) and recurrent FN admissions (IRR, 1.53; 95% CI, 1.10-2.12, P=0.01). Accounting for combined age and NCI risk status, obesity was a risk factor for treatment-requiring hypertension (OR, 3.90; 95% CI, 1.19-12.76, P=0.02), insulin-requiring hyperglycemia (OR, 3.92; 95% CI, 1.39-11.05, P=0.01), and FN admission (OR, 2.92; 95% CI, 1.27-6.73, P=0.01). During pre-maintenance chemotherapy for ALL, obesity is a risk factor for the development of hypertension, hyperglycemia, and FN admissions. This research provides implications for augmented preventive and supportive care guidelines in obese ALL patients.

To assess the prognostic role of different inflammatory indices on the outcome of cancer patients with COVID-19. Sixty-two adults and 22 pediatric cancer patients with COVID-19 infection were assessed for the prognostic value of certain inflammatory indices including the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), derived NLR (dNLR), systemic inflammation index (SII), mean platelet volume to platelet ratio (MPR), C-reactive protein to lymphocyte ratio (CRP/L), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIRI), and neutrophil to lymphocyte, platelet ratio (NLPR). Data were correlated to patients’ outcome regarding ICU admission, and incidence of mortality. Increased CRP/L ratio in adult COVID-19 cancer patients was significantly associated with inferior survival [152 (19–2253) in non-survivors, compared to 27.4 (0.8–681) in survivors (P = 0.033)]. It achieved a sensitivity (60%) and a specificity (90.2%) at a cut-off 152, while it achieved a sensitivity of 60% and specificity 95.1% at a cut-off 252 (AUC 0.795, P = 0.033). When combining both CRP/L and NLPR for the prediction of poor outcome in adult cancer patients with COVID19, the sensitivity increased to 80% and the specificity was 70.7% (AUC 0.805, P = 0.027). Increased incidence of ICU admission in pediatric cancer patients associated significantly with the severity of covid19 infection, decreased mean corpuscular hemoglobin (MCH) < 28.3, increased red cell distribution width (RDW) > 16, lymphopenia < 1.04, pseudo Pelger-Huet appearance, and PLR < 196.4 (P = 0.004, P = 0.040, P = 0.029, P = 0. 0.039, P = 0.050, and P = 0.040; respectively). The mean corpuscular volume (MCV), MCH, and RDW could be useful prognostic markers for poor outcome in COVID-19 pediatric cancer patients (P < 0.05 for all). Increased both CRP/L and NLPR associated significantly with poor survival in adult COVID-19 cancer patients, while PLR associated significantly with ICU admission in pediatric COVID-19 cancer patients.