Pediatric Malignancies Research Articles

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignant tumors in children: Initial experience in a single institution.

Peritoneal malignant tumors in children are rare but commonly associated with disease progression and poor outcome. The successful treatment experience of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in adult peritoneal carcinoma has been applied to pediatric peritoneal malignancy in recent years. However, patients with desmoplastic small round cell tumor (DSRCT) accounted for the majority of patients treated with CRS and HIPEC in previous studies. The role of CRS and HIPEC remains controversial due to the rarity of the disease and the limited sample size of studies. Additionally, the cases using CRS and HIPEC except DSRCT were mainly small case reports with unclear outcomes. We present our experience in the treatment of pediatric peritoneal malignancies using CRS and HIPEC, with more emphasis on the safety, feasibility, and short-term outcome. A retrospective query from December 2019 to February 2022 identified 19 children with peritoneal malignancies who underwent CRS and HIPEC in our institution. Clinical characteristics, therapies, and outcomes were summarized and analyzed. The median age of the patients was 6.4 years (range, 0.7-13.9 years). The histologic types included rhabdomyosarcoma (7), Wilms tumor (2), clear cell sarcoma of the kidney (2), undifferentiated sarcoma (2), immature teratoma (1), peritoneal serous carcinoma (1), malignant rhabdoid of the kidney (1), malignant germ cell tumor (1), neuroblastoma (1), and epithelioid inflammatory myofibroblast sarcoma (1). Seven patients underwent initial operation, and 12 patients received reoperation for tumor recurrence. The median peritoneal carcinomatosis index was 5 (range, 2-21). There were no perioperative deaths or life-threatening complications of CRS and HIPEC. Two patients had grade 3 complications of wound infection and wound dehiscence. With a median follow-up time of 14 months (range, 1.5-31 months), 14 patients were alive, and 5 died of tumor recurrence. Of the 14 patients who were alive, 2 relapsed after CRS and HIPEC and then received radiotherapy and molecular-targeted therapy or chemotherapy. CRS and HIPEC are safe and feasible in children, without increasing serious complications in the peri- and postoperative periods. The complication is acceptable. The short-term outcome shows possible effectiveness in pediatric peritoneal malignant tumors. The long-term effectiveness needs to be verified by additional cases and long-term follow-ups.

Continuing Challenges and Current Issues of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Case Report

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, accounting for nearly 75% of all newly diagnosed leukemias and 25% of all malignancies in childhood. The Philadelphia chromosome-positive Ph+ is a rare subtype of ALL, considered one of its poorest subgroups, and accounts for 3-5% of pediatric ALL. Dentists should acquire some background information about leukemia and its oral manifestations for better dental care. Commonly reported oral manifestations include regional lymphadenopathy, mucous membrane petechiae and ecchymoses, gingival bleeding, gingival hypertrophy, pallor, and non-specific ulcerations. In this case report, we aim to raise awareness among dentists and discuss the orthodontic management of a pediatric patient with Ph+ ALL. The patient was cleared by her treating physician, and treatment was done in the dental chair. Treatment included restorations of all carious teeth, reinforcement of oral hygiene, a series of removable appliances to correct the anterior cross-bite, and in-office bleaching.

Efficacy and Safety of Stereotactic Body Radiation Therapy for Pediatric Malignancies: The LITE-SABR Systematic Review and Meta-Analysis

PurposeLimited data are currently available on clinical outcomes after stereotactic body radiation therapy (SBRT) for pediatric and adolescent and young adult (AYA) patients with cancer. We aimed to perform a systematic review and study-level meta-analysis to characterize associated local control (LC), progression-free survival (PFS), overall survival, and toxicity after SBRT. Methods and MaterialsRelevant studies were queried using a Population, Intervention, Control, Outcomes, Study Design (PICOS)/Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)/Meta-analysis of Observational Studies in Epidemiology (MOOSE) selection criteria. Primary outcomes were 1-year and 2-year LC as well as incidence of acute and late grade 3 to 5 toxicities, with secondary outcomes of 1-year overall survival and 1-year PFS. Outcome effect sizes were estimated with weighted random effects meta-analyses. Mixed-effects weighted regression models were performed to examine potential correlations between biologically effective dose (BED10), LC, and toxicity incidence. ResultsAcross 9 published studies, we identified 142 pediatric and AYA patients with 217 lesions that were treated with SBRT. Estimated 1-year and 2-year LC rates were 83.5% (95% confidence interval, 70.9%-96.2%) and 74.0% (95% CI, 64.6%-83.4%), respectively, with an estimated acute and late grade 3 to 5 toxicity rate of 2.9% (95% CI, 0.4%-5.4%; all grade 3). The estimated 1-year OS and PFS rates were 75.4% (95% CI, 54.5%-96.3%) and 27.1% (95% CI, 17.3%-37.0%), respectively. On meta-regression, higher BED10 was correlated with improved 2-year LC with every 10 Gy10 increase in BED10 associated with a 5% improvement in 2-year LC (P = .02) in sarcoma-predominant cohorts. ConclusionsSBRT provided durable LC for pediatric and AYA patients with cancer with minimal severe toxicities. Dose escalation may result in improved LC for sarcoma-predominant cohorts without a subsequent increase in toxicity. However, further investigations with patient-level data and prospective inquiries are indicated to better define the role of SBRT based on patient and tumor-specific characteristics.

Clinical profile and renal function following unilateral nephrectomy in pediatric malignancy – After completion of therapy

Clinical profile and renal function following unilateral nephrectomy in pediatric malignancy – After completion of therapy

Non-viral nitric oxide-based gene therapy improves perfusion and liposomal doxorubicin sonopermeation in neuroblastoma models.

Neuroblastoma (NB) is a pediatric malignancy that accounts for 15% of cancer-related childhood mortality. High-risk NB requires an aggressive chemoradiotherapy regimen that causes significant off-target toxicity. Despite this invasive treatment, many patients either relapse or do not respond adequately. Recent studies suggest that improving tumor perfusion can enhance drug accumulation and distribution within the tumor tissue, potentially augmenting treatment effects without inflicting systemic toxicity. Accordingly, methods that transiently increase tumor perfusion prior to treatment may help combat this disease. Here, we show the use of gene therapy to confer inducible nitric oxide synthase (iNOS) expression solely in the tumor space, using focused ultrasound targeting. NOS catalyzes the reaction that generates nitric oxide (NO), a potent endogenous vasodilator. This study reports the development of a targeted non-viral image-guided platform to deliver iNOS-expressing plasmid DNA (pDNA) to vascular endothelial cells encasing tumor blood vessels. Following transfection, longitudinal quantitative contrast-enhanced ultrasound (qCEUS) imaging revealed an increase in tumor perfusion over 72 h, attributed to elevated intratumoral iNOS expression. Methods: To construct a gene delivery vector, cationic ultrasound-responsive agents (known as "microbubbles") were employed to carry pDNA in circulation and transfect tumor vascular endothelial cells in vivo using focused ultrasound (FUS) energy. This was followed by liposomal doxorubicin (L-DOX) treatment. The post-transfection tumor response was monitored longitudinally using qCEUS imaging to determine relative changes in blood volumes and perfusion rates. After therapy, ex vivo analysis of tumors was performed to examine the bioeffects associated with iNOS expression. Results: By combining FUS therapy with cationic ultrasound contrast agents (UCAs), we achieved selective intratumoral transfection of pDNA encoding the iNOS enzyme. While transitory, the degree of expression was sufficient to induce significant increases in tumoral perfusion, to appreciably enhance the chemotherapeutic payload and to extend survival time in an orthotopic xenograft model. Conclusion: We have demonstrated the ability of a novel targeted non-viral gene therapy strategy to enhance tumor perfusion and improve L-DOX delivery to NB xenografts. While our results demonstrate that transiently increasing tumor perfusion improves liposome-encapsulated chemotherapeutic uptake and distribution, we expect that our iNOS gene delivery paradigm can also significantly improve radio and immunotherapies by increasing the delivery of radiosensitizers and immunomodulators, potentially improving upon current NB treatment without concomitant adverse effects. Our findings further suggest that qCEUS imaging can effectively monitor changes in tumor perfusion in vivo, allowing the identification of an ideal time-point to administer therapy.

Prevalence of Antibiotic Resistance in Pediatric Malignancy Patients: A Two-Year Retrospective Study in Basra City

Prevalence of Antibiotic Resistance in Pediatric Malignancy Patients: A Two-Year Retrospective Study in Basra City

RNA-Sequencing Combined With Genome-Wide Allele-Specific Expression Patterning Identifies ZNF44 Variants as a Potential New Driver Gene for Pediatric Neuroblastoma.

Neuroblastoma (NB) is one of the children's most common solid tumors, accounting for approximately 8% of pediatric malignancies and 15% of childhood cancer deaths. Somatic mutations in several genes, such as ALK, have been associated with NB progression and can facilitate the discovery of novel therapeutic strategies. However, the differential expression of mutated and wild-type alleles on the transcriptome level is poorly studied. This study analyzed 219 whole-exome sequencing datasets with somatic mutations detected by MuTect from paired normal and tumor samples. We prioritized mutations in 8 candidate genes (RIMS4, RUSC2, ALK, MYCN, PTPN11, ALOX12B, ZNF44, and CNGB1) as potential driver mutations. We further confirmed the presence of allele-specific expression of the somatic mutations in NB with integrated analysis of 127 RNA-seq samples (of which 85 also had DNA-seq data available), including MYCN, ALK, and PTPN11. The allele-specific expression of mutations suggests that the same somatic mutation may have different effects on the clinical outcomes of tumors. Our study suggests 2 novel variants of ZNF44 as a novel candidate driver gene for NB.

A Clinicopathological Study with Risk-Stratified Staging of Pediatric Hepatoblastoma: A 5-Year Experience from a Tertiary Cancer Center.

Hepatoblastoma encompasses 1% of pediatric malignancies and is the most common liver malignancy in children. Ninety percent of cases are younger than 5 years of age. Clinical and pathological risk stratification forms a crucial role in determining the treatment strategy. This study aimed to assess the clinicopathological profile of hepatoblastoma with risk stratification and follow-up in children. A retrospective evaluation was performed on all pediatric patients diagnosed as hepatoblastoma between 2016 and 2020 in our institution. Clinical, radiological, biochemical, pathological, and treatment data were analyzed. Cases were stratified based on the SIOPEL protocol and compared with the outcome. The median age of all children was 1 year, the male-to-female ratio was 2.3:1, and elevated α-fetoprotein (AFP) was observed in all cases. SIOPEL risk stratification showed that 50% of children were at high risk. The histopathological types were fetal (30%), embryonal (20%), and macrotrabecular (5%) patterns under epithelial type and mixed epithelial and mesenchymal type (45%) with 1 case showing teratoid features. During the follow-up period, 6 out of the 7 children who died, belonged to the high-risk SIOPEL category, and 5 presented a mixed epithelial and mesenchymal pattern. Our study found a significant correlation between clinicopathological data, histopathological patterns, and outcomes. Accordingly, histopathological patterns could be considered one of the criteria for risk stratification. Histopathological risk stratification indicators (such as SIOPEL and PRETEXT) have strong prognostic and predictive outcomes; hence, our study emphasizes such parameters to aid oncologists.

Spectrum of paediatric malignancies and treatment in COVID era – Our institutional experience

Spectrum of paediatric malignancies and treatment in COVID era – Our institutional experience

Outcomes of autologous haematopoetic stem cell transplantation for paediatric malignancies: Single-centre experience

Outcomes of autologous haematopoetic stem cell transplantation for paediatric malignancies: Single-centre experience

Mild Hypophosphatemia-Associated Conditions in Children: The Need for a Comprehensive Approach.

To better understand the causes of hypophosphatemia in children, we evaluated all serum phosphate tests performed in a tertiary hospital with unexpected but persistent temporary or isolated hypophosphatemia over an 18 year period. We collected 29,279 phosphate tests from 21,398 patients, of which 268 (1.2%) had at least one result showing hypophosphatemia. We found that endocrinopathies (n = 60), tumors (n = 10), and vitamin D deficiency (n = 3) were the medical conditions most commonly associated with mild hypophosphatemia, but in many patients the cause was unclear. Among patients with endocrinopathies, those with diabetes mellitus were found to have lower mean serum phosphate levels (mean 3.4 mg/dL) than those with short stature (3.7 mg/dL) or thyroid disorders (3.7 mg/dL). In addition, we found a correlation between glycemia and phosphatemia in patients with diabetes. However, despite the potential relevance of monitoring phosphate homeostasis and the underlying etiologic mechanisms, renal phosphate losses were estimated in less than 5% of patients with hypophosphatemia. In the pediatric age group, malignancies, hypovitaminosis D, and endocrine disorders, mostly diabetes, were the most common causes of hypophosphatemia. This real-world study also shows that hypophosphatemia is frequently neglected and inadequately evaluated by pediatricians, which emphasizes the need for more education and awareness about this condition to prevent its potentially deleterious consequences.

Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.

Over the past two decades, novel hallmarks of cancer have been described, including the altered epigenetic landscape of malignant diseases. In addition to the methylation and hyd-roxymethylation of DNA, numerous novel forms of histone modifications and nucleosome remodeling have been discovered, giving rise to a wide variety of targeted therapeutic interventions. DNA hypomethylating drugs, histone deacetylase inhibitors and agents targeting histone methylation machinery are of distinguished clinical significance. The major focus of this review is placed on targeted epigenetic interventions in the most common pediatric malignancies, including acute leukemias, brain and kidney tumors, neuroblastoma and soft tissue sarcomas. Upcoming novel challenges include specificity and potential undesirable side effects. Different epigenetic patterns of pediatric and adult cancers should be noted. Biological significance of epigenetic alterations highly depends on the tissue microenvironment and widespread interactions. An individualized treatment approach requires detailed genetic, epigenetic and metabolomic evaluation of cancer. Advances in molecular technologies and clinical translation may contribute to the development of novel pediatric anticancer treatment strategies, aiming for improved survival and better patient quality of life.

The CHK2 kinase is recurrently mutated and functionally impaired in the germline of pediatric cancer patients.

Predisposing CHEK2 germline variants are associated with various adult-type malignancies, whereas their impact on cancer susceptibility in childhood cancer is unclear. To understand the frequency of germline variants in the CHEK2 gene and their impact on pediatric malignancies, we used whole-exome sequencing to search for CHEK2 variants in the germlines of 418 children diagnosed with cancer in our clinics. Moreover, we performed functional analysis of the pathogenic CHEK2 variants to analyze the effect of the alterations on CHK2 protein function. We detected a CHEK2 germline variant in 32/418 (7.7%) pediatric cancer patients and 46.8% of them had leukemia. Functional analysis of the pathogenic variants revealed that 5 pathogenic variants impaired CHK2 protein function. 6/32 patients carried one of these clearly damaging CHEK2 variants and two of them harbored a matching family history of cancer. In conclusion, we detected germline CHEK2 variants in 7.7% of all pediatric cancer patients, of which a minority but still relevant fraction of approximately 20% had a profound impact on protein expression or its phosphorylation after irradiation-induced DNA damage. Accordingly, we conclude that CHEK2 variants increase the risk for not only adult-onset but also pediatric cancer.

1342. Serial Microbial Cell-Free DNA Next Generation Sequencing (NGS) As A Means of Diagnosis and Monitoring of Clinical Response To Treatment Of Invasive Fungal Infections (IFI) In Immunocompromised Pediatric Patients

Abstract Background IFIs are a leading cause of morbidity and mortality in immunocompromised pediatric patients. Early diagnosis and initiation of therapy is critical for treatment success but is often hindered by difficulty obtaining tissue samples, lack of growth on culture and time required for culture positivity. Non-culture methods such as aspergillus galactomannan and 1-3 B-D glucan lack sensitivity and specificity. NGS has shown promise in identifying a wide array of pathogens. The Karius test is a NGS which can identify viral, bacterial, and fungal infections by detecting cell free pathogen DNA in peripheral blood with a rapid turnaround time. Over the past few years we have used the Karius test as an adjunct to our standard of care in the workup and treatment of IFI in our oncology population Methods We report our experience in using serial NGS testing for diagnosis of IFI as well as a means for monitoring clinical response to treatment in our pediatric hematological malignancy population. Results Between 12/1/20-12/31/21, 5 patients had serial NGS for IFI. Most common indication for testing was prolonged fever and neutropenia with abnormal imaging. Initial diagnosis was made by NGS in all 5 patients. All had tissue biopsies with fungal elements seen on path in 4 of 5 patients. Culture was positive in 3 of 5 patients (2 days, 10 days and 12 days post NGS testing result). One patient with persistent positive NGS testing was found to have resistance to treatment drug on susceptibility testing and subsequently had negative NGS testing once appropriate antifungals were started. A second patient had sterilization of cultures with concomitant negative NGS results but developed increasing fungal copies on NGS testing followed by positive culture when chemotherapy was resumed and subsequently died due to his infection. 4 of 5 patients had serial negative follow up NGS and continue to do well. Summary of Diagnostic Work-Up Conclusion In our small series of patients, NGS testing allowed for rapid diagnosis of IFIs and corresponded to clinical response to treatment. Future prospective studies will be needed to further evaluate the use of NGS in this patient population. Disclosures All Authors: No reported disclosures.

Pediatric Head and Neck Malignancies

Head and neck masses represents a common clinical entity in pediatric age group. In general, these masses are classified in to developmental, inflammatory, or neoplastic. Having a working knowledge of these lesions in head and neck region & conducting a thorough history & physical examinations generally enable the clinician to simplify an appropriate workup and establish a diagnosis. The differential diagnosis is wide-ranging, and expeditiously distinguishing the benign from malignant masses is difficult for instituting a timely multidisciplinary approach to the management of malignancy. Malignancy of the head and neck account for approximately 5% of all childhood carcinomas. This review aims to discuss the most common head and neck malignancies in childhood. The evidence for the diagnosis and management of childhood, head and neck malignancy is summarized. The rarity of these tumors are inevitably results in a paucity of high-level evidence to guide the treatment. Keywords: Children, Head and neck malignancy, Lymphoma, Malignancy, Rhabdomyosarcoma

Magnolol regulates miR-200c-3p to inhibit epithelial–mesenchymal transition and retinoblastoma progression by modulating the ZEB1/E-cadherin axis in vitro and in vivo

BackgroundRetinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3–4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear. PurposeThe study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro. MethodsThe 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, β-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo. ResultsMagnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/β-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma. ConclusionMagnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.

Germline risk factors for second malignant neoplasms after treatment for pediatric hematologic malignancies.

Survivors of childhood hematologic malignancies are at a substantially higher risk of developing subsequent neoplasms (SNs) when compared with the general population. SNs commonly observed in this population include basal cell carcinoma, brain tumors, thyroid cancer, breast cancer, bone tumors, and sarcoma. Radiation is the primary therapeutic exposure associated with the development of these SNs. There is emerging evidence of an association between chemotherapeutic exposures (alkylating agents/anthracyclines) and the development of SNs. Despite a strong dose-dependent association between therapeutic exposures and SN risk, there is significant interindividual variability in the risk for SNs for any given dose of therapeutic exposure. This interindividual variability in risk suggests the role of genetic susceptibility. This article describes the clinical and molecular epidemiology of SNs commonly observed in survivors of childhood hematologic malignancies and also highlights some of the work focusing on the development of risk prediction models to facilitate targeted interventions.

Development and validation of a cuproptosis-related lncRNA model correlated to the cancer-associated fibroblasts enable the prediction prognosis of patients with osteosarcoma

BackgroundOsteosarcoma is the most common primary pediatric and adolescent bone malignancy. An imbalance in copper homeostasis caused by copper ion accumulation could increase intracellular toxicity and regulate cancer cell growth. This study aimed to identify long non-coding RNAs (lncRNAs) associated with cuproptosis to predict prognosis and target drug use to improve patient survival. MethodsRNA sequencing and relevant clinical information of ninety-three osteosarcoma patients were obtained from the TARGET database. We then identified thirteen prognostic cuproptosis-related lncRNAs(CRLncs) using coexpression and univariate Cox analyses. The prognostic risk model with three CRLncs was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. Patients were divided into low-risk and high-risk subgroups using the median risk score. The tumor microenvironment (TME) and immune status of identified subgroups were analyzed using ESTIMATE, CIBERSORT, MCP-counter, xCELL, EPIC, and ssGSEA analyses. Functional analyses were conducted to elucidate the underlying mechanisms, including GO, KEGG, GSVA, and GSEA analyses. Also, the relationships between the model, tumor immunity, and drug sensitivity were explored. Lastly, the expression level of ZNF37BP, AL353759.1, and AC005034.5 was validated in vitro. ResultsWe constructed a model containing three CRLncs (ZNF37BP, AL353759.1, and AC005034.5) and validated its excellent prognostic and predictive power. The AUC curves for 1-year, 3-year, and 5-year survival probabilities were 0.76, 0.84, and 0.89, respectively. Patients in the high-risk group had a shorter overall survival (OS) time than those in the low-risk. The stroma score and cancer-associated fibroblasts (CAFs) were significantly higher in the low-risk group. Immune cells such as T cells CD4 naive, T cells gamma delta, NK cells resting, dendritic cells resting, and mast cells activated were significantly upregulated in the high-risk group. Based on functional analyses, the PI3K-Akt pathway was identified as a critical metabolic pathway in osteosarcoma. Additionally, we obtained three potentially effective drugs for OS: erlotinib, MP470, and WH-4-023 targeting the PI3K-Akt pathway. The expression level of ZNF37BP was significantly elevated in OS cell lines than in normal osteoblast hFOB1.19 cells, and that of ATP7A, LIPT1, AL353759.1, and AC005034.5 were decreased considerably in OS cell lines. ConclusionCuproptosis-related lncRNAs are correlated with the CAFs of osteosarcoma, and this could serve as a foundation for OS survival prediction and treatment.

Risk factors and screening for neurocognitive impacts of therapy

Long-term survivors of pediatric hematologic malignancies are at elevated risk for neurocognitive impairment. Such impairment manifests in different ways at different times during survivorship, with deficits in processing speed, attention, and memory often appearing before deficits in executive function, intelligence, and academics. Survivors exposed to therapies that directly target the central nervous system (CNS), as is the case in acute lymphoblastic leukemia, may demonstrate subtle deficits during frontline therapy, and these deficits may grow and evolve over time. Survivors who do not receive CNS-directed therapies (eg, Hodgkin lymphoma) are also at elevated risk for neurocognitive impairment, although the influence on brain function is indirect through cancer therapy impact on systemic organ function vital to brain health (eg, cardiopulmonary morbidity). Over the course of the survivor's life span, the presence and impact of neurocognitive deficits will be determined by a complex interaction between premorbid development and environment, cancer therapy and clinical care, and posttreatment recovery and health. The timing and type of these treatment and health events will dictate the approach to screening and monitoring for neurocognitive impairment.

Study of Hemato-morphological Features in Neuroblastoma Infiltrating Marrow.

Objective Neuroblastoma typically affects children within the first 5 years of life and accounts for 10% of all pediatric malignancies. Neuroblastoma at onset may manifest as a localized or metastatic illness. The aim of this study was to identify hematomorphological features in neuroblastoma infiltrating marrow as well as to ascertain the prevalence of bone marrow infiltration in neuroblastoma. Materials and Methods This retrospective study included newly diagnosed 79 cases of neuroblastoma, which were referred for bone marrow examination for the staging of the disease. Medical records were retrieved to acquire hematomorphological findings of peripheral blood and bone marrow smears. Statistical Package for Social Sciences, IBM Inc., USA, version 21.0 was used to analyze the data. Results The interquartile age range of neuroblastoma cases was 24.0 to 72.0 months (median = 48 months) with a male to female ratio of 2.7:1. Also, 55.6% (44/79) of cases in the study population showed evidence of marrow infiltration. The bone marrow infiltration was significantly linked to thrombocytopenia ( p = 0.043) and nucleated red blood cells ( p = 0.003) in peripheral blood. The bone marrow smears of cases with infiltration showed a significant shift to the left in the myeloid series ( p = 0.001) and an increased number of erythroid cells ( p = 0.001). Conclusion For neuroblastoma patients, a diligent, exhaustive search for infiltrating cells in bone marrow is advised if thrombocytopenia or nucleated red blood cells are identified on a peripheral blood smear and bone marrow smears showed myeloid left shift with an increased number of erythroid cells.