Overall Survival Rate Of Children Research Articles

Clinical features and prognostic factors of advanced myelodysplastic syndromes in children

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 μg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

Single-cell analyses of metastatic bone marrow in human neuroblastoma reveals microenvironmental remodeling and metastatic signature.

Neuroblastoma is an aggressive pediatric cancer with a high rate of metastasis to the BM. Despite intensive treatments including high-dose chemotherapy, the overall survival rate for children with metastatic neuroblastoma remains dismal. Understanding the cellular and molecular mechanisms of the metastatic tumor microenvironment is crucial for developing new therapies and improving clinical outcomes. Here, we used single-cell RNA-Seq to characterize immune and tumor cell alterations in neuroblastoma BM metastases by comparative analysis with patients without metastases. Our results reveal remodeling of the immune cell populations and reprogramming of gene expression profiles in the metastatic niche. In particular, within the BM metastatic niche, we observed the enrichment of immune cells, including tumor-associated neutrophils, macrophages, and exhausted T cells, as well as an increased number of Tregs and a decreased number of B cells. Furthermore, we highlighted cell communication between tumor cells and immune cell populations, and we identified prognostic markers in malignant cells that are associated with worse clinical outcomes in 3 independent neuroblastoma cohorts. Our results provide insight into the cellular, compositional, and transcriptional shifts underlying neuroblastoma BM metastases that contribute to the development of new therapeutic strategies.

Phosphorylation of human glioma-associated oncogene 1 on Ser937 regulates Sonic Hedgehog signaling in medulloblastoma

Aberrant activation of sonic hedgehog (SHH) signaling and its effector transcriptional factor GLI1 are essential for oncogenesis of SHH-dependent medulloblastoma (MBSHH) and basal cell carcinoma (BCC). Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1’s proteasomal degradation and negates the transcription of SHH signaling. As a result, Gli1S941E loss-of-function knock-in significantly reduces the incidence and severity of smoothened-M2 transgene-induced spontaneous MBSHH, whereas Gli1S941A gain-of-function knock-in phenocopies Gli1 transgene in causing BCC-like proliferation in skin. Correspondingly, phospho-Ser937-GLI1, a destabilized form of GLI1, positively correlates to the overall survival rate of children with MBSHH. Together, these findings indicate that SHH-induced p38α inactivation and subsequent GLI1 dephosphorylation and stabilization in controlling SHH signaling and may provide avenues for future interventions of MBSHH and BCC.

A comparative assessment of open and laparoscopic techniques in managing congenital diaphragmatic hernias in newborns

Introduction. The authors share their experience in managing congenital diaphragmatic hernias (CDH) in newborns with open and thoracoscopic techniques.Material and methods. From 2012 to 2022, 46 newborns with CDH were admitted to Kuraev Children’s Republican Clinical Hospital in Makhachkala (Russia). 5 children died before surgery, they were excluded from the study. In order to compare outcomes after treatment, all children operated on by the authors were divided into two groups depending on the technique of surgical CDH correction. Newborns from Group 1 (n = 23; 56%) were operated with open access. Newborns from Group 2 (n = 18; 44%) were operated with thoracoscopic access.Results. A comparative evaluation of outcomes after thoracoscopic and open techniques for correcting CDH was made. By the literature, the overall survival rate of children with CDH has increased from 50–60% to 80–90%. The author consider, that it is largely due to the application of extracorporeal membrane oxygenation (ECMO) and nitric oxide to compensate pulmonary hypertension which is the main factor decreasing the postoperative mortality. In this case, physicians prescribed Sildenafil; the survival rate in Group 1 was 48% and in Group 2 – 67%. The authors noted that the mortality rate depended on the size of diaphragm dome defect, on the number of abdominal organs in the pleural cavity. Besides, the place where a child was operated on – in the resuscitation department or not – was also an important factor.Conclusion. Thoracoscopy is a preferred approach for managing CDH because it does not need dissection of a large array of muscles; otherwise, later, in the postoperative period, it can impair the respiratory function. Early postoperative mortality in newborns is caused by hemodynamic disorders, so it is recommended to perform surgical interventions in this group of patients in the resuscitation department. To prevent hemodynamic disorders, it is recommended to install a pleural drainage intraoperatively in all patients with CDH. The authors underline that in their study postoperative course, rate of intraoperative and postoperative complications, as well as mortality rate did not have any statistically significant differences in the compared groups (p0.05). Despite a marked progress in CDH management, large diaphragm defects still is an unsolved problem.

Pediatric Acute Lymphoblastic Leukemia: Russian Experience with the ALL-IC BFM 2002 Protocol

Background: Treatment protocols for pediatric acute lymphoblastic leukemia (ALL) developed by the BFM (Berlin-FrankfurtMunster) group are among the most effective in the world. The longstanding overall survival rate of children with ALL is more than 90%. The highly successful treatment results obtained for ALL are the reason that the ALL-IC BFM 2002 protocol is widely used in Russia. Aim: This study presents the results of the Russian multicenter study for pediatric ALL treatment by the ALL ICBFM 2002 rotocol. Materials and Methods: In total, 433 patients with primary ALL from 10 Russian pediatric hematology/oncology clinics were included in retrospective and prospective studies from 01.11.2003 to 12.10.2021. The ages of the patients ranged from 3 months to 21 years. All patients were treated according to the ALL IC-BFM 2002 protocol. The overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were assessed on 11.12.2021. Results: An overwhelming majority of patients, 97.9% (n=424), achieved clinical and laboratory remission by 33 days of treatment based on the ALL IC-BFM 2002 protocol. The 10-year OS was 91.8+/-1.5%, the RFS was 87.4+/-1.8%, and the EFS was 84.1+/-1.9%. The results of the 10-year OS in the standard-risk and intermediate-risk groups were 92+/-1.7%, and 93.1+/- 3.0%, respectively, and the percentage of relapse in the high-risk group was 71.1+/-11.1%. Conclusion: The ALL-IC BFM 2002 protocol for pediatric ALL could be performed in Russian federal and regional clinics. The treatment results for ALL using the ALL-IC BFM 2002 protocol are dramatic and comparable to those of leading clinics in Europe and the United States. To improve the survival rate in high-risk groups of patients, it is necessary to use additional risk-stratifying factors such as minimal residual disease (MRD).

Malignant invasion of the cerebrospinal fluid in adult and paediatric patients with haematological and solid malignancies: a monocentric retrospective study

ABSTRACT Objectives In this study, we describe the clinical presentation, the cerebrospinal fluid (CSF) characteristics and outcome of children and adults with leptomeningeal invasion due to haematological and solid malignancies. Methods Routine CSF samples analyzed from 2008 to 2018 at our institution were retrospectively reviewed for the presence of malignant cells based on cytomorphological analysis. Results Leptomeningeal invasion was identified in 212 patients: 45 children versus 167 adults, and 92 haematological versus 120 solid malignancies. Leukaemic invasion in childhood was mainly due to ALL, and lymphoma invasion was often due to a high-grade B-cell lymphoma in adults. Metastatic invasion by solid tumours was almost exclusively seen in adults. Patients suffered most frequently from cranial neuropathy and headache (both 32%), while asymptomatic presentations were seen mainly in children (33%) and haematological malignancies (17%). Laboratory CSF parameters often showed an elevated WBC count (87%), total protein (74%) and lactate (76%) and a decreased glucose (77%). These deviations were especially found in solid malignancies (>84%) and adults (>82%). Brain and/or spinal cord imaging was more often suggestive for the leptomeningeal invasion in solid than in haematological malignancies (86% vs. 46%). The 5-year overall survival (OS) rates for patients with haematological and solid malignancies were 21.5% and 5.9%, respectively. The 5-year OS rate for children (55.6%) was significantly better than for adults (3.5%). Conclusion Leptomeningeal invasion is more often asymptomatic, and CSF parameters and imaging are more often normal in children and haematological malignancies than in adults and solid malignancies, possibly leading to underdiagnosis.

Trends in Childhood Cancer in Kuwait: Data From the 2004-2017 Registry.

Background and objectiveThere is a lack of updated data regarding pediatric cancer in Kuwait, with no separate childhood cancer registry available in the country prior to this study. We aimed to determine the trends in different cancer types with respect to international statistics, in order to understand their nature and identify gaps in their diagnosis and management.MethodsThis retrospective study was based on data obtained from the first national childhood cancer registry of the National Bank of Kuwait (NBK) Specialized Hospital for Children, the only hospital that manages pediatric cancer patients in Kuwait. The registry included the data of all children with cancer in Kuwait from 2004 to 2017 and had complete data files.FindingsThe total number of patients in the childhood cancer registry was 1,387. A total of 1,009 files met our eligibility criteria. In 2017, the incidence of childhood leukemia was determined to be six per 100,000 people, and for other cancers, it was 12.6 per 100,000 people. The most common cancer was leukemia (457 patients), followed by lymphoma (141 patients), and brain tumors (92 patients). The majority of children received chemotherapy (n=891, 88.3%). Post induction or treatment, the majority of patients achieved complete remission (n=790, 78.3%). The overall survival rate of children with cancer was around 80%. Major complications developed in 9% of patients.ConclusionThese findings highlight the importance of hospital‐based cancer registries. Active data management programs are essential to monitor outcomes, measure the effectiveness of current practice, and improve the quality of care.

EVALUATION OF THE EFFECTIVENESS OF RETINOBLASTOMA THERAPY IN CHILDREN

The paper presents the results of treatment of 113 children with retinoblastoma who were treated at the Scientific Center of Pediatrics and Pediatric Surgery under the RBA-2003 program from 2013 to 2020. Verification of the diagnosis of retinoblastoma was carried out according to international criteria. When analyzing the results of the study, the overall survival rate of children with retinoblastoma was 79%. The therapeutic protocol is highly effective, allowing to obtain high rates of overall survival in the vast majority of patients. The effectiveness of treatment in stage I was 97%, in stage II-90%, in stage III-80%. Early detection of RB promotes early initiation of antitumor therapy, the survival rate of which is more than 90% (I degree - 97%, II degree - 90%). Keywords: retinoblastoma in children, early diagnosis, organ-preserving therapy.

Clinical features of neuroblastoma: an analysis of 44 children

Objective To study the clinical features of neuroblastoma (NB) and the factors influencing survival rate. Methods A total of 44 children with NB who were admitted from April 2016 to February 2020 were enrolled as research subjects. A retrospective analysis was performed on their medical data and follow-up data. Results The common clinical symptoms of these 44 children were fever (10/44, 23%), mass (9/44, 20%), abdominal pain (8/44, 18%), cough (7/44, 16%), pale complexion (3/44, 7%), claudication (2/44, 5%), and abnormal activity (2/44, 5%). According to the INSS stage, 2 children (4%) had stage I NB, 5 children (11%) had stage II NB, 5 children (11%) had stage III NB, and 32 children (73%) had stage IV NB. The mean follow-up time was (15.3±1.5) months, with a recurrence rate of 20% and an overall survival rate of 82%. Among the 44 children, 29 (66%) achieved event-free survival and 7 (16%) had survival with tumor. The univariate analysis showed that a pathological type of NB and an increase in serum neuron-specific enolase (NSE) decreased the overall survival rate of children with NB (P Conclusions The clinical symptoms of children with NB are not specific at the first visit. Fever, abdominal pain, and mass are common symptoms, and there is a high proportion of children in the advanced stage. The pathological type of NB and an increase in serum NSE may be associated with a reduction in the overall survival rate of children with NB.

Clinical Prognostic Factors Analysis of Initially Treated AML Children with t(8;21)/RUNX1-RUNX1T1

To investigate the clinical prognostic factors of initially-treated AML children with t(8;21)/RUNX1-RUNX1T1+. Clinical data of 41 initially-treated AML children with t(8;21)/RUNX1-RUNX1T1+ in our hospital in period from January 2009 to January 2017 were retrospectively analyzed. The baseline clinical characteristics, cumulative recurrence, event-free survival (EFS) and overall survival (OS) were recorded, and the influencing factors of prognosis were evaluated by χ2 test and Cox regression model. The complete remission (CR) rates in the first course and the second course of induction chemotherapy were respectively 82.93% (34/41) and 97.56% (40/41). The median EFS time and OS time were 30 months and 31 months respectively. The EFS rate and OS rate of children with CR after the first treatment course were significantly higher than those of children without CR (P＜0.05). The EFS rate of male children was significantly higher than that of female children (P＜0.05). The OS rate of children < 10 years old was significantly higher than that of children≥10 years old (P＜0.05). The expression level of RUNX1-RUNX1T1 gene after the second induction remission was the influencing factor of cumulative recurrence rate, EFS rate and OS rate in children (P＜0.05). Multivariate analysis by Cox regression model showed that the decreased levels of RUNX1-RUNX1T1 gene expression < 3 log after the second induction remission was the independent risk factor for EFS rate and OS rate in children (P＜0.05). The cumulative recurrence rate of children with RUNX1-RUNX1T1 gene expression increase for＞1 log after decreased 3 log was significantly higher than that of children with≤1 log (P＜0.05). Iuithally-treated AML children with t(8;21)/RUNX1-RUNX1T1+ show the fine clinical prognosis after standard chemotherapy. The expression level of RUNX1-RUNX1T1 gene should be closely relates with the recurrence and long-term survival of AML children.

Lymphoblastic predominance of blastic phase in children with chronic myeloid leukaemia treated with imatinib: A report from the I-CML-Ped Study

BackgroundChronic myeloid leukaemia (CML) is a rare disease in children. The frequency and outcome of children evolving to accelerated phase (AP) or blastic phase (BP) under treatment with imatinib is unknown. The aim of the current study is to assess the incidence of progression from CML in chronic phase with imatinib frontline in a paediatric setting and describe the management and outcome of these patients. Patients and methodsIn the I-CML-Ped Study database (www.clinicaltrials.gov, #NCT01281735), 19 of 339 paediatric patients in chronic phase treated with imatinib in the frontline evolved to CML-AP or CML-BP. ResultsWith a median follow-up of 38 months (range: 2–190 months), the cumulative incidence of progression at 1 and 3 years was 3% (confidence interval [CI] 95%: 1–5%) and 7% (CI 95%: 4–11%), respectively. We observed a large predominance of lymphoid-BP (70%) over myeloid-BP (30%) with imatinib in frontline therapy. Sixteen patients underwent haematopoietic stem cell transplantation, and eight were treated with a tyrosine kinase inhibitor after transplant. Only the transplanted patients are alive. The 5-year overall survival rate of children with CML-AP/BP is 44%, with no statistical difference between the lymphoid-BP and myeloid-BP outcome. ConclusionChildren evolving to AP or BP under treatment with imatinib have a very poor prognosis with an overall survival under 50%, much worse than children with advanced phase at diagnosis.

Efficacy and prognostic factors in children with non-core binding factor acute myeloid leukemia

To compare the efficacy of the CAMS-2005 and CAMS-2009 regimens in treating children with non-core binding factor acute myeloid leukemia (non-CBF AML) and to study the prognosis factors. A total of 161 children who were initially diagnosed with non-CBF AML from April 2005 to December 2015 were enrolled as study subjects, and were divided into a CAMS-2005 regimen group (n=52) and a CAMS-2009 regimen group (n=109) according to the chemotherapy regimen provided. The efficacy was retrospectively compared between the two groups. The complete remission (CR) rate at the first course of treatment was higher in the CAMS-2009 regimen group than that in the CMAS-2005 regimen group (63.3% vs 46.2%; P<0.05). There were no significant differences between the two groups in treatment-related mortality rate (11.9% vs 17.3%), recurrence rate (27.5% vs 28.8%), and three-year overall survival (OS) rate (44%±5% vs 28%±6%) (P>0.05). Children who achieved CR at the first course of treatment had significantly higher OS and event-free survival rates than those who did not achieved CR (P<0.01). The CAMS-2009 regimen is superior to the CAMS-2005 regimen in improving the CR rate in children with non-CBF AML after induction treatment. Whether CR is achieved at the first course of treatment can affect the OS rate of children with non-CBF AML.

Characteristics of systemic lupus erythematosus and lupus nephritis in children in the Republic of Belarus and the Republic of Tatarstan

Systemic lupus erythematosus is an autoimmune disease characterized by a pronounced polymorphism of clinical manifestations. Lupus nephritis is the most severe manifestation of the disease. The article presents a retrospective analysis of the cases of systemic lupus erythematosus and assessment of the clinical manifestations of the disease and variants of lupus nephritis in children in the Republics of Belarus and Tatarstan. The authors analyzed 60 cases of systemic lupus erythematosus, lupus nephritis. All patients had at least 4 of the 11 diagnostic criteria proposed by the American College of rheumatology (ACR, 1997), and 35 patients had a morphologically verified nephritis. It was found that the disease in children developed very actively with fast multi-organ involvement and it required aggressive therapy with several immunosuppressive drugs. During follow-up, the percentage of patients with renal damage increased, so renal function should be controlled in all patients with systemic lupus erythematosus, especially with early onset. Lupus nephritis is combined with extrarenal manifestations and it is difficult to diagnose when it begins with kidney damage. The overall survival rate of children with systemic lupus erythematosus is closely related to the severity of renal manifestations. Lupus nephritis is a serious problem that requires early aggressive intervention and continuous maintenance therapy.

Children and Adults with Steroid-Refractory Acute Graft-Versus-Host Disease Respond to Treatment with the Mesenchymal Stroma Cell Preparation “MSC-FFM”: Treatment Results for 92 Consecutive Patients

Introduction: Since the seminal paper of LeBlanc in 2008, despite several negative studies, the scientific community has retained optimism with respect to the usefulness of mesenchymal stroma cells (MSCs) in refractory acute graft-versus-host disease (GvHD). A prevailing theme of past studies was that, while pediatric GvHD responded to MSCs, adult GvHD did not. As reported, we developed proprietary protocols GMP-quality MSC production from bone marrow (BM) mononuclear cells expanded in platelet lysate-enriched media.Patients and Methods: We present treatment data with MSC-FFM for 61 children/adolescents and 31 adults with either “only” steroid-refractory (SR) GvHD (27%) or GvHD which had additionally proven refractory to up to five additional lines of therapy (MR-GvHD) (73%). Pediatric patients tended to have more MR-GvHD than adults. Patients from 23 centers in 6 countries were included. Most patients had severe GvHD (37% °III, 59% °IV, Glucksberg scale). 31 patients (34%) were female,61 male (66%). 69 have a malignant disease (75%), and 23 a non-malignant (25%) disease as indication for transplantation. Donors were MSD (n=21, 23%), MUD (n=56, 61%), haploidentical (n=14, 15%), and 1 MMUD (1%).Patients received myeloablative conditioning with TBI-, Treosulfan-, Busulfan- and Fludarabine-based regimen, with serotherapy, mostly ATG. 89% of patients had had immunosuppression for GvHD prophylaxis, 13% CSA alone, 49% CSA+MTX or MMF; or others (n=15, 16%). Median onset of aGvHD was at 40 days (range: 6-280 d), another 28 days (range: 5-380) until the first infusion of MSC-FFM. Recommended dose and interval is 4 weekly doses of 1-2M MSC/kg body weight; the average patient received only 3 doses, the interval approximately staggered as recommended, with a median dose of 1.4M MSC/kg. Any reduction in GvHD activity by at least one full grade was classified as a partial (PR), absence of any degree of GvHD as a complete response (CR).Results: Day-28 response rates were 84%/25%/59% overall (OR)/CR/PR for children and 80%/35%/45% for adults resulting in a day-28 response rate for the entire cohort: 82%/28%/54%). At last follow-up (LFU) many of the pediatric responders had continued to improve from partial to complete response to response rates of 84%/59%/25% OR/CR/PR, in adults responses were largely unchanged (77%/35%/42%; LFU for the entire cohort: 81%/51%/30%). GvHD °III and °IV were equally likely to respond or resolve. Looking at response rates of SR- vs. MR-GvHD, of the SR-GvHD 96% responded (MR-GvHD: 81%), as well as early and LFU responses in SR-GvHD were more likely to be complete responses (60% and 72% for SR-GvHD, 16% and 43% for MR-GvHD, day-28 and LFU, respectively).Day-28-response was highly predictive of long-term responsiveness, in that only one non-responder on day 28 achieved a response long term, and only two initial partial responders' GvHD relapsed to the same degree of severity as before MSC treatment.The historical expected survival probability for patients with steroid-refractory severe GvHD being in the order of 20% at 6 months. The patients reported here with °III or °IV aGVHD achieved 6-month overall survival probabilities of 65% and 61%, respectively. In total 6 patients relapsed and died (of note: only 69 patients were at risk), 28 deaths were treatment-related. 6-month overall survival rates for children and adults were 68% and 54%, respectively (n.s.). In terms of adverse reactions to MSC-FFM, one case each of spontaneously remitting headache and nausea/vomiting were reported shortly after infusion of the thawed cells. Both events occurred in children and were possibly related to the rapid infusion of DMSO-containing ice-cold fluid and not the active substance.Conclusion: MSC-FFM emanates as a highly efficacious treatment for severe pediatric and adult advanced GvHD, with OR in excess of 80% and survival rates approximating those of patients without GvHD. The very low relapse mortality may suggest that severe GvHD effectively suppresses leukemic recurrence. Better and faster responses of SR- vs. MR-GvHD make a case for early treatment with MSC-FFM. DisclosuresBader:Medac: Patents & Royalties, Research Funding; Cellgene: Consultancy; Neovii: Research Funding; Riemser: Research Funding; Novartis: Consultancy, Speakers Bureau. Kuci:Medac: Patents & Royalties. Kuci:Medac: Patents & Royalties. Bug:Amgen: Honoraria; Jazz Pharmaceuticals: Other: Travel Grant; Neovii: Other: Travel Grant; Astellas Pharma: Other: Travel Grant; Janssen: Other: Travel Grant; Celgene: Honoraria; Novartis Pharma: Honoraria, Research Funding. Lang:Miltenyi Biotec: Patents & Royalties, Research Funding. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Seifried:Medac: Other: BSD owns IP and is contract manufacturer; Uniqure BV: Research Funding. Bonig:Kiadis Pharma: Consultancy.

Treatment and prognosis analysis of 56 cases of childhood hepatoblastoma in advanced stage with pulmonary metastasis

Objective To explore the treatment and prognosis of advanced stage childhood hepatoblastoma with pulmonary metastasis. Methods Fifty-six cases of advanced stage hepatoblastoma with pulmonary metastasis diagnosed through pathology from April 2006 to June 2014 in Department of Pediatrics, Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled, among them 33 cases were males and 23 cases were females, and the median age was 2.33 years old (1 month-15 years and 1 month old). The clinical effects of multidisciplinary therapy were analyzed. Results (1)Follow-up studies were conducted till December 2016, in which 21 cases of 56 children achieved complete remission, the complete remission rate was 37.5% (21/56 cases), while 12 cases were partial remission and 14 cases were deceased, and the effective rate reached 58.9% (33/56 cases). The follow-up period of 41 children were over 24 months, in which the 2-year free event survival (EFS) rate was 37.5%, 2-year overall survi-val (OS)rate was 75.0%, 5-year survival rate was 42.4%, and the 95% average survival confidence interval was 35.7-55.9 months.(2)The OS rate of children with small age (≤3 years old) was 88.1%(36/42 cases), the ove-rall prognosis was better than that of >3 years old children (35.7%, 5/14 cases) (P=0.003). The survival rate of children with complete tumor resection [OS rate was 89.2%(33/37 cases)] was significantly higher than that of the incomplete excision [OS rate was 47.4%(9/19 cases)], and the difference was statistically significant(P=0.001). The prognosis of epithelial type cases was better than that of other types, and the difference was statistically significant(P<0.05), while the fetal type prognosis was the best, and the difference was statistically significant(χ2=8.56, P=0.014). The growth of alpha fetoprotein was negatively correlated with the clinical efficacy and prognosis(r=-0.468, P=0.023). Conclusions Lung is the most common metastatic site of hepatoblastoma, and the marginal lung metastasis is more common.With insidious onset and poor prognosis.Therefore, it should be treated with early diagnosis and multidisciplinary therapy to improve prognosis. Key words: Hepatoblastoma; Pulmonary metastasis; Chemotherapy; Child; Alpha fetoprotein; Prognosis

Pediatric Medulloblastoma: a Case of Recurrent Disease and Resiliency

As advances in treatment have evolved over the past several years, a diagnosis of a brain tumor in childhood is no longer a universal lethal disease. In fact, the overall survival rate of children with medulloblastoma brain tumors is over 70% (Ward et al., CA Cancer J Clin 64:83–103, 2014). Medical and cognitive late effects are common in this population, although advances in treatment have focused on reducing the detrimental effects of cranial radiation therapy (RT) and chemotherapy. This article will provide an overview of the epidemiology, pathophysiology, and treatment approaches to medulloblastoma (the most frequently occurring embryonic brain tumor; Ostrom et al., Neuro Oncol 17:iv1–iv62, 2015), as well as complications, common medical and neurocognitive late effects, and protective factors. Innovative and emerging treatments and strategies to improve neuropsychological function and quality of life are also reviewed. We present a case study that highlights many of these challenges and conclude with a conceptualization that integrates the research reviewed with the unique characteristics of this most extraordinary young man.

Clinical and epidemiological characteristics of children with germ cell tumors: A single center experience in a developing country.

İncesoy-Özdemir S, Ertem U, Şahin G, Bozkurt C, Yüksek N, Ören AC, Balkaya E, Alkan A. Clinical and epidemiological characteristics of children with germ cell tumors: A single center experience in a developing country. Turk J Pediatr 2017; 59: 410-417. Germ cell tumor (GCT) is a rare malignancy accounting for 2-3% of all pediatric tumors. The overall survival rate of children and adolescents with GCT is more than 80% after adopting combined therapy. The aim of this study is to review clinical presentation, management, and outcome in a single-center series with extracranial GCT. Clinical characteristics, pathologic presentations, and survival outcomes of 101 children with GCT, treated at our hospital from 1988 to 2011, were analyzed. Sixty-two of patients were female and 39 of them were male. Fifty-eight (57%) patients had gonadal tumor (24 testicular, 34 ovarian), 43 (43%) extragonadal. Histologically, teratomas were found most frequently (26 mature, 10 immature), followed by yolk sac tumors (n: 33), mixed malignant tumors (n: 13), embryonal carcinoma (n: 10), disgerminoma (n: 8) and seminoma (n: 1). Twenty-six patients were diagnosed as mature teratoma and we excluded them in the evaluation of staging and survival. Five-year overall and relaps-free survival were 80.3% (mean follow-up time: 215.8 months) and 73.4% (mean follow-up time: 176.2 months), respectively. Five-year survival rates were 93.2% and 90.2% in malign GCTs diagnosed after 1999.

CDC20siRNA and paclitaxel co-loaded nanometric liposomes of a nipecotic acid-derived cationic amphiphile inhibit xenografted neuroblastoma.

Despite significant recent progress in the area of translational genomics of neuroblastoma, the overall survival rates for children with high-risk NB continue to be not more than 5 years due to tumor relapse and/or drug-resistant tumors. Herein we report on the development of a neuroblastoma targeting nanometric (130-150 nm) circulation stable liposomal system prepared from a novel nipecotic acid-derived cationic amphiphile (NACA). The size ranges of liposomes (130-150 nm) were confirmed by both dynamic light scattering and transmission electron microscopy. The findings in the gel electrophoresis assay revealed that siRNAs encapsulated within the liposomes of NACA (with 90% entrapment efficiency) are protected from attack by RNase. Cellular uptake experiments using FAM-siRNA loaded liposomes of NACA showed the liposomal entry in human neuroblastoma cells (IMR-32) to be mediated via the GABAA receptor. CDC20siRNA-loaded liposomes of NACA caused significantly higher CDC20 gene silencing efficiency in IMR-32 cells compared to CDC20 gene knockdown efficiency mediated by CDC20siRNA-loaded control non-targeting liposomes (NTL). The findings in the annexin-V binding based flow cytometric apoptosis assay and MTT-based cellular cytotoxicity assay support the notion that pronounced (80%) neuroblastoma cell death upon treatment with CDC20siRNA & PTX co-loaded liposomes of NACA presumably originates from enhanced apoptosis of cells. Importantly, intravenously administered CDC20siRNA & PTX co-loaded liposomes of NACA significantly inhibited growth of xenografted human neuroblastoma in athymic nude mice. The presently disclosed strategy of co-delivering potent anticancer siRNA and small molecule chemotherapeutics using liposomes of NACA opens a new door for combating the dreaded disease of neuroblastoma.

Incidence and survival of childhood leukemia in Recife, Brazil: A population-based analysis.

Leukemia is the most common pediatric cancer with incidence rates of around 48 per million for children under 15 years of age. The median age-adjusted incidence rate (AAIR) in children aged 0-14 years in Brazil is 53.3 per million. While overall survival rates for children with leukemia have improved significantly, data for incidence, trends, and relative survival among children and adolescents with leukemia in Recife, Brazil, remain incomplete, which hampers our analyses and provision of the best healthcare. The objective of this report is to provide that data. Data from the Population-Based Cancer Registry of Recife were analyzed from 1998 to 2007. Our analyses included frequencies and AAIR, together with age-specific incidence rates for all leukemias, acute lymphoblastic leukemia, and acute myeloid leukemia. To evaluate incidence trends, joinpoint regression, including annual average percent change, were analyzed. Relative survival was calculated using the life-table method. One hundred seventy-five cases were identified, 51% in females. The review reduced the not otherwise specified (NOS) leukemia category by 50% and diagnosis by death certificate only from 5.7% to 1.1%. The AAIR for leukemia was 41.1 per million, with a peak among children aged 1-4 (78.3 per million). Incidence trends during the period were stable. The five-year relative survival rate was 69.8%. These data represent the incidence rate and survival of childhood leukemia in Recife, located in the northeast region of Brazil, using a high-quality database.

Estimated Late Health Outcomes in Children Newly Diagnosed with Mature B-Cell Non-Hodgkin Lymphoma Treated with Contemporary LMB Chemotherapy Based upon Similarly Treated Participants in the Childhood Cancer Survivor Study (CCSS)

Introduction: Since the mid-1990’s, overall survival rates for children diagnosed with mature B-cell non-Hodgkin lymphoma (B-NHL) have exceeded 90%, due in large part to the widespread utilization of the LMB chemotherapy regimen. As a result, a population of survivors living beyond 5 years from diagnosis and treatment with this regimen is emerging, providing the first opportunity to study late-occurring and chronic health outcomes following contemporary B-NHL therapy. Methods: Late health outcomes and health status were self-reported among CCSS participants who were 5-year survivors of childhood B-NHL and whose treatment exposures were consistent with LMB-defined risk-groups (A - low; B - intermediate; and C - high risk). Combinations of individual chemotherapy agents (cyclophosphamide [CPM], vincristine, prednisone, doxorubicin [doxo], high-dose methotrexate [HD-MTX], cytarabine, and etoposide) and respective cumulative doses (for CPM, doxo, HD-MTX, and etoposide) were abstracted from medical records. Chronic health conditions occurring ≥5 years from cancer diagnosis were graded per the Common Terminology Criteria for Adverse Events (version 4.03). Decreased fertility was defined as failure to achieve or sire a pregnancy after ≥1 year of trying among survivors of childbearing age (15-44 years). Health status outcomes were obtained from validated questionnaires. Standardized mortality ratios (SMRs) were estimated. Cox and logistic regression models (adjusted for age, sex, and race) provided hazard (HR) and odds ratios (OR) and 95% confidence intervals (CI) of health conditions and status compared to a sibling comparison group (n=4,023). Results: We identified 94 B-NHL survivors (median age 10 [range 2-20] years at diagnosis, 24 [10-39] years at evaluation, 14 [7-26] years post diagnosis), for which pertinent LMB treatment exposures are included in Table 1. Compared to siblings, survivors were more likely to be male (79% vs. 48%, p<0.001), younger at evaluation (24.3 ± 6.1 vs. 26.7 ± 9.2 years, p<0.001), and non-white race (22% vs 13%, p=0.006). Thirty-five (37%) survivors had ≥1 chronic condition (grades 1-5); a 4-fold increased risk (HR 4.1, 95% CI: 2.9-5.8) compared to siblings (Group A HR 2.6, 95% CI 1.2-5.6, Group B HR 5.2, 95% CI 3.1-8.6, and Group C HR 4.2, 95% CI 2.4-7.6). The most frequently occurring conditions were obesity (24%) and decreased fertility (10%). Excluding these, Group B (HR 5.3, 95% CI 1.6-17.3) and Group C (HR 5.7, 95% CI 1.7-19.0) survivors remained at increased risk of having ≥1 chronic condition. Group A survivors showed a similar HR without statistical significance (HR 4.0, 95% CI 0.5-31.3). Three survivors died during study follow-up (SMR 6.5, 95% CI 1.3-19.0), only one died due to a non-cancer related cause of death. All Groups (A-C) were more likely than siblings to report impaired functional status (OR 11.2, 95% CI 3.5-35.6; 4.5, 95% CI 1.5-13.1; and 15.1, 95% CI 6.0-37.8, respectively). Groups B and C survivors were more likely to report poor mental health (OR 2.9, 95% CI 1.0-8.6 and 3.7, 95% CI 1.0-12.9, respectively), while Group B survivors were more likely to report poor general health (OR 5.1, 95% CI 2.2-11.9). No associations with activity limitations (p’s>0.1) or sociodemographic differences (educational level less than a college degree, p’s>0.1; household income less than $60,000/year, p’s>0.1) were identified in any Groups. Cancer-related pain and anxiety did not differ in Groups B or C compared to survivors in Group A (p=0.9 and 0.2, respectively). Conclusions: Despite excellent survival rates, children diagnosed with B-NHL and treated with contemporary LMB chemotherapy regimens are at risk for chronic health conditions and health status limitations by 14 years from diagnosis. Studies exploring the trajectory of these findings and the impact of early interventions are needed to inform future frontline treatment protocols. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.