Circulating myeloid-derived suppressor cells in pediatric solid tumor patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9565-9565
Author(s):  
John M. Goldberg ◽  
Abdel-Aziz Zidan ◽  
Rabia Siddiqi ◽  
Myriam Zayas ◽  
Camille D. Brown ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Solid Tumors ◽  
Pediatric Cancer ◽  
Suppressor Cells ◽  
Prognostic Indicators ◽  
Healthy Children ◽  
Myeloid Derived Suppressor Cells ◽  
Children With Cancer ◽  
Pediatric Cancer Patients ◽  
The Mean

9565 Background: Cure rates have reached a plateau for many pediatric solid tumors. Identifying new therapeutic targets, biomarkers of response and prognostic indicators should improve clinical outcomes. Accumulation of myeloid derived suppressor cells (MDSCs) is an important mechanism of tumor mediated immune evasion. Increased levels of MDSCs in adult cancer patients correlate with a worse prognosis, and decrease in levels with treatment is associated with benefit. Little is known about MDSCs in childhood, or in children with cancer. This pilot measured levels of MDSCs in pediatric patients with cancer and healthy children. Methods: We enrolled subjects using an Institutional Review Board approved protocol after obtaining informed consent. Blood was obtained from 14 children with newly diagnosed or recurrent solid tumors at start of therapy. In 10 of these patients, levels were also drawn after therapy. Blood was obtained once from 6 healthy children in a primary care office. Samples were obtained concurrently with complete blood counts. MDSCs were measured on fresh whole blood and were defined as Lin-1+/HLADR-/CD 33+/CD11b+/ by flow. Total MDSC numbers were then calculated. Results: The mean total number of MDSCs was 596 cells/ul at diagnosis for the 14 children with cancer and 170 cells/ul for the 6 healthy children (t(18) = 3.02, p = .0073). For the 10 children with cancer who had repeat values measured after treatment, MDSCs decreased in 4 and increased in 6. The mean initial MDSC count for these children was 494 cells/ul, and the mean post treatment count was 1716 cells/ul (t(9) = 1.81, p = .1036). Larger change scores tended to be associated with children treated with alkylator therapy followed by G-CSF. The results for percent MDSC in white cells mirrored those of total number. Conclusions: Circulating MDSCs were higher in pediatric cancer patients than healthy controls. Cancer treatment did not reliably reduce MDSC levels. After some treatments, the levels increased, potentially increasing immune tolerance. Further research is needed to determine if circulating MDSCs are a reliable predictive or prognostic marker in pediatric cancer, and whether they represent a potential target for therapeutic intervention.

scholarly journals Age related defects in NK cell immunity revealed by deep immune profiling of pediatric cancer patients

2020 ◽  
Author(s):  
Eleni Syrimi ◽  
Naeem Khan ◽  
Paul Murray ◽  
Carrie Willcox ◽  
Tracey Haigh ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Patients ◽  
Pediatric Cancer ◽  
Nk Cell ◽  
Effector Memory ◽  
High Dimensional ◽  
Healthy Children ◽  
Children With Cancer ◽  
Systemic Immunity ◽  
Pediatric Cancer Patients

AbstractSystemic immunity plays an important role in cancer immune surveillance and therapy but there is little detailed knowledge about the immune status of healthy children or children with cancer. We performed a high dimensional single cell analysis of systemic immunity in pediatric cancer patients and age-matched healthy children. In young children with cancer (age < 8years) NK cells were decreased in frequency, maturity, expression of perforin and granzyme-B, and were less cytotoxic in ex vivo assays. NK cell activity was restored after in vitro culture with interleukin-2. In contrast, older children with cancer (>8 years old) had decreased naive CD4 and CD8 T-cells with concomitant increases in effector memory and T effector memory RA-revertant (TEMRA) T-cells. These immunological changes in pediatric cancer patients are relevant to the better understanding of how cancers diagnosed in childhood interact with systemic immunity and could inform the development and application of effective immune-modulating therapies in the pediatric population.One Sentence SummaryHigh dimensional analysis of systemic immunity in pediatric cancer patients reveals clinically relevant immune changes in NK and T-cells that vary with patient age.

Prospective agnostic germline testing in pediatric cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1589-1589
Author(s):  
Elise Fiala ◽  
Jennifer Kennedy ◽  
Yelena Kemel ◽  
Audrey Mauguen ◽  
Diana Mandelker ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Solid Tumors ◽  
Pediatric Cancer ◽  
Spinal Tumors ◽  
Cancer History ◽  
Pediatric Solid Tumors ◽  
Pediatric Cancer Patients ◽  
High Penetrance ◽  
Tumor Types ◽  
Dominant Genes

1589 Background: We report our large cohort of pediatric cancer patients undergoing prospective agnostic germline sequencing. Our dataset is a significant addition to the 1,573 children reported to date who have undergone agnostic germline sequencing in previous large sequencing studies, each with ascertainment bias. Methods: 676 patients with pediatric solid tumors underwent matched tumor-normal targeted DNA sequencing from July 2015 to February 2020. At least 76 genes associated with cancer predisposition were analyzed in the germline, and variants were classified per American College of Medical Genetics guidelines. Pathogenic and likely pathogenic (P/LP) variants were reported to patients/families, who were offered genetic counseling and cascade testing with screening recommendations and referral to a surveillance clinic as appropriate. Results: One or more P/LP variants were found in 17% (115/676) of individuals when including low, moderate and high penetrance mutations in recessive and dominant genes, or 12% (81/676) when including moderate and high penetrance mutations in dominant genes. P/LP variants were detected in 40% (21/53) of patients with retinoblastomas, 8% (13/161) with neuroblastomas/ganglioneuroblastomas, 13% (14/112) with brain/spinal tumors, 8% (20/245) with sarcomas, and 12% (13/105) with other solid tumors. The most frequent mutations were in RB1 (n = 28) and TP53 (n = 8) in patients with associated tumors. Of patients with moderate/high penetrance mutations, 30% (24/81) had unexpected tumor types, with potential therapeutic relevance in 58% (14/24) including BRCA1 n = 2, BRCA2 n = 3, RAD51D n = 1, ATM n = 1 MLH1 n = 1, MSH2 n = 1, MSH6 n = 1, PMS2 n = 3, and SUFU n = 1. Two patients received immunotherapy based on their germline finding. Conclusions: P/LP germline variants are frequently present in patients with pediatric cancer. We are contributing significantly to the cohort size of agnostic sequencing in pediatric cancers. Our experience is similar to other studies with a ~12% detection rate of moderate and high penetrance mutations. Moderate/high penetrance mutations were concordant with the patient’s cancer history in 70% of cases, higher than previously reported, likely due to an enrichment of retinoblastoma. While many mutations are identified in patients with associated tumor types, a large proportion of mutations are unexpected based on the patient’s history. Clinical actionability of these findings may include screening, risk reduction, family planning, and increasingly targeted therapies.

Physical Activity in Pediatric Cancer patients with solid tumors (PAPEC): Trial rationale and design

2013 ◽  
Vol 36 (1) ◽  
pp. 106-115 ◽  
Author(s):  
Luisa Soares-Miranda ◽  
Carmen Fiuza-Luces ◽  
Alvaro Lassaletta ◽  
Elena Santana-Sosa ◽  
Julio R. Padilla ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Pediatric Cancer ◽  
Pediatric Cancer Patients

Staphylococcus aureus Sepsis in Children With Cancer

PEDIATRICS ◽  
1978 ◽  
Vol 61 (2) ◽  
pp. 231-234
Author(s):  
Stephan Ladisch ◽  
Philip A. Pizzo
Keyword(s):  
Staphylococcus Aureus ◽  
Cancer Patients ◽  
Median Duration ◽  
Pediatric Cancer ◽  
Primary Infection ◽  
Children With Cancer ◽  
Pediatric Cancer Patients

Seventy episodes of Staphylococcus aureus sepsis occurring over a nine-year period in pediatric cancer patients are reviewed. Prominent findings at the time of diagnosis included fever, granulocytopenia, and active malignancy. Probable or suspected sites of primary infection were present in 40 episodes (57%). Serious direct complications of staphylococcal sepsis included only three cases of pneumonia and one of myositis. However, second infections by other organisms developed in 16 episodes (24%), resulting in nine nonstaphylococcal infectious deaths during therapy. Endocarditis and osteomyelitis never occurred in this group of patients. The median duration of antistaphylococcal therapy was 15 days.

Assessment of acute kidney injury by urinary β2-MG and NAG in pediatric cancer patients prescribed with Cisplatin, Carboplatin, and Ifosfamide as the chemotherapeutic agents

2020 ◽  
Author(s):  
Alireza Moafi ◽  
Hanieh Basirkazeruni ◽  
Nahid Reisi ◽  
Moein Dehbashi ◽  
Leila Ghanbarinia ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cancer Patients ◽  
Pediatric Cancer ◽  
Age Groups ◽  
Kidney Injury ◽  
Chemotherapeutic Agents ◽  
Pediatric Cancer Patients ◽  
The Mean ◽  
Beta 2 Microglobulin ◽  
Kidney Injury Molecule 1

Background: Acute kidney injury (AKI) is defined as a failure in renal function leading to insufficiency of fluid and electrolyte homeostasis. Thus, sensitive biomarkers of renal tubular injury are needed to detect AKI earlier. In this study, urinary beta 2-microglobulin (β2-MG) and urinary N-acetyl-β-D-glucosaminidase (NAG) were evaluated for AKI prognosis/diagnosis in pediatric patients suffering different cancers prescribed with Ifosfamide, Ifosfamide plus Carboplatin, and Ifosfamide plus Cisplatin. Materials and Methods: In this prospective study done in Isfahan, Iran, urinary β2-MG, urinary NAG, blood urea nitrogen (BUN), and serum and urinary creatinine (Cr) were measured in 40 pediatric cancer patients less than 16 years old in three age groups during 61 courses of chemotherapy on day 0, three and six after the treatment. Results: Using ANOVA and t-test, the mean levels of urinary β2-MG (p= 0.001), urinary β2-MG/Cr (p= 0.003) and urinary NAG/Cr (p= 0.001), before and on day six of the treatment were statistically significant (p< 0.05). Also, the mean levels of BUN (p= 0.01), urinary β2-MG (p= 0.001), β2-MG/Cr (p= 0.001) and NAG/Cr (p= 0.004) based on the gender groups, the mean levels of urinary NAG (p=0.001), NAG/Cr (p= 0.001) and β2-MG/Cr (p= 0.008) based on three age groups, and the mean levels of serum Cr (p= 0.047), urinary β2-MG (p= 0.005), β2-MG/Cr (p= 0.032) and NAG/Cr (p= 0.032) based on the Ifosfamide dosage were statistically significant during the time of the treatment. Conclusion: Urinary β2-MG, urinary β2-MG/Cr, and urinary NAG/Cr are more significant biomarkers than serum Cr in earlier diagnosis and treatment of AKI in cancer patients. However, urinary NAG should be further studied to prove its reliability for AKI prognosis/diagnosis. It is suggested that urinary NAG can be used along with other renal biomarkers such as urinary β2-MG, kidney injury molecule-1(KIM-1), or interleukin-18 (IL-18) for AKI prognosis/diagnosis.

scholarly journals Trends in age- and sex-adjusted body mass index and the prevalence of malnutrition in children with cancer over 42 months after diagnosis: a single-center cohort study

2019 ◽  
Vol 179 (1) ◽  
pp. 91-98
Author(s):  
Henri Aarnivala ◽  
Tytti Pokka ◽  
Riina Soininen ◽  
Merja Möttönen ◽  
Arja Harila-Saari ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Nutritional Status ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Body Mass ◽  
Pediatric Cancer ◽  
Drug Toxicity ◽  
Myeloid Leukemia ◽  
Pediatric Cancer Patients ◽  
Age And Sex

Abstract The adequate nutritional status of pediatric cancer patients is particularly important to enable them to cope with the demands of the disease and its treatment and to maintain normal growth. Malnutrition and obesity have both been associated with reduced survival and increased drug toxicity. We investigated trends in the age- and sex-adjusted body mass index (ISO-BMI) and the prevalence of malnutrition in a Finnish cohort of 139 consecutive children receiving chemotherapy for cancer, with a follow-up period of 42 months after diagnosis. In total, 28% (39/139) of the patients experienced malnutrition (ISO-BMI < 17 or > 10% weight loss), and 12% (16/139) had a nasogastric tube or underwent gastrostomy. Patients with acute or chronic myeloid leukemia (5/10), central nervous system (CNS) tumors (5/13), or solid tumors (13/31) most frequently suffered from malnutrition. There was a significant increase in the ISO-BMI of patients with acute lymphoblastic leukemia (ALL) (+ 2.1 kg/m2) and lymphomas (+ 2.4 kg/m2) during the first 6 months, and the ISO-BMI of patients with ALL remained higher at 42 months compared to baseline (+ 1.9 kg/m2). Conclusion: The cumulative incidence of malnutrition in Finnish pediatric cancer patients is comparable to that reported in other populations. The nutritional status of patients with acute myeloid leukemia, CNS tumors, or solid tumors should be monitored with extra care to facilitate early intervention in the case of impending malnutrition.What is known:• Both malnutrition and obesity are associated with reduced survival and increased drug toxicity in pediatric cancer patients.What is new:• Overall, 28 % of Finnish children receiving chemotherapy for cancer suffer from malnutrition during the first 42 months following the initial cancer diagnosis. • ISO-BMI curves from initial diagnosis to 42 months after diagnosis are provided for patients with different types of cancer.

scholarly journals Plasma free amino acid profiling as metabolomic diagnostic and prognostic biomarker in paediatric cancer patients: a follow-up study

Amino Acids ◽  
2020 ◽  
Author(s):  
Anna Synakiewicz ◽  
Anna Stanislawska-Sachadyn ◽  
Malgorzata Sawicka-Zukowska ◽  
Grazyna Galezowska ◽  
Joanna Ratajczyk ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Pediatric Cancer ◽  
Prognostic Biomarker ◽  
Cell Metabolism ◽  
Healthy Children ◽  
Paediatric Cancer ◽  
Pediatric Cancer Patients ◽  
Amino Acid Profiling ◽  
Cancer Cell Metabolism

AbstractAmino acids (AAs) play a crucial role in cancer cell metabolism. Levels of 22 plasma AAs at the time of diagnosis and after treatment were established among 39 pediatric cancer patients and 33 healthy children. Glutamic acid levels decreased and tryptophan levels increased during treatment. Cancer patients presented significantly lower levels of glutamine and leucine post-treatment while levels of 12 other AAs were higher comparing to controls. Results suggest that plasma free AA profile may serve as a prognostic biomarker.

scholarly journals 2689. Stenotrphomonas maltophilia, The Hidden Threat Among Pediatric Cancer Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S944-S945
Author(s):  
Youssef Madney. Said ◽  
Riham Abdelaziz ◽  
Shimaa Samir ◽  
Mervat Elanany
Keyword(s):  
Mortality Rate ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Pediatric Cancer ◽  
Hematological Malignancies ◽  
Lymphoblastic Leukemia ◽  
Significant Risk ◽  
Attributable Mortality ◽  
Cell Transplant ◽  
Pediatric Cancer Patients

Abstract Background Stenotrophomonas maltophilia is an emerging nosocomial pathogen in immunocompromised patients. Although S. maltophilia exhibits limited pathogenicity in immunocompetent hosts, it has been shown to cause fatal infections in patients with malignancies. The objective of this study to analyze the clinical characteristics, susceptibility pattern, and treatment outcome of S. maltophilia among pediatric cancer patients. Methods Retrospective analysis including all pediatric cancer patients treated at children cancer hospital Egypt (CCHE) with S. maltophilia bloodstream infection from June 2013 till June 2018. Results 281 isolates among 135 pediatric cancer patients. Most are hematological malignancies 67(50%), solid tumors 55 (40%) and post-transplant 13(10%). Most common hematological malignancies were acute lymphoblastic leukemia 34 patients (25%) while brain tumor was the most common solid tumors 20 patients (15%). The spectrum of infections includes bacteremia in 61 patients (45%) catheter-related in 34 (25%), pneumonia in 22 (16%), skin and soft-tissue infection in 11(8%) meningitis in 5 (3%) and disseminated infections with multiorgan involvement in 4(3%) patients. 46 patients (34%) was admitted in intensive care unit (ICU), 67 inpatient (50%), 11 (8%) stem cell transplant unit and 11 patient (8%) from emergency and outpatient department. The isolates revealed 80% susceptibility to Trimethoprim-Sulfamethoxazole (TMP-SMX), 77% to ciprofloxacin, 50% to cefepime and ceftazidime, 63% to amikacin, 48% to piperacillin–tazobactam, 93% to colistin, 97% to tigecycline. Day 30 mortality (Crude mortality rate) 33 patients (25%) while S. maltophilia attributable mortality (died within 7 days of culture isolation) was 17 patients (13%). Patients with pneumonia, (TMP-SMX) resistance and ICU admission were associated with a significant risk of mortality. Conclusion Stenotrphomonas bloodstream is a serious pathogen and hidden threat among pediatric cancer patients associated with high mortality rate. Disclosures All authors: No reported disclosures.

scholarly journals Nutritional Status of Pediatric Cancer Patients at Diagnosis and Correlations with Treatment, Clinical Outcome and the Long-Term Growth and Health of Survivors

Children ◽  
2020 ◽  
Vol 7 (11) ◽  
pp. 218
Author(s):  
Vassiliki Diakatou ◽  
Tonia Vassilakou
Keyword(s):  
Quality Of Life ◽  
Clinical Outcome ◽  
Nutritional Status ◽  
Cancer Patients ◽  
Pediatric Cancer ◽  
Nutritional Assessment ◽  
Positive Impact ◽  
Children With Cancer ◽  
Pediatric Cancer Patients

Malnutrition is caused either by cancer itself or by its treatment, and affects the clinical outcome, the quality of life (QOL), and the overall survival (OS) of the patient. However, malnutrition in children with cancer should not be accepted or tolerated as an inevitable procedure at any stage of the disease. A review of the international literature from 2014 to 2019 was performed. Despite the difficulty of accurately assessing the prevalence of malnutrition, poor nutritional status has adverse effects from diagnosis to subsequent survival. Nutritional status (NS) at diagnosis relates to undernutrition, while correlations with clinical outcome are still unclear. Malnutrition adversely affects health-related quality of life (HRQOL) in children with cancer and collective evidence constantly shows poor nutritional quality in childhood cancer survivors (CCSs). Nutritional assessment and early intervention in pediatric cancer patients could minimize the side effects of treatment, improve their survival, and reduce the risk of nutritional morbidity with a positive impact on QOL, in view of the potentially manageable nature of this risk factor.

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