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The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors.

ABSTRACT: Central nervous system (CNS) malignancies represent 20% of all childhood cancers. To improve outcomes in infants and children with high-risk disease, treatment can include adjuvant chemotherapy and early autologous peripheral blood human progenitor cell collection (AHPCC), followed by high-dose chemotherapy and stem cell rescue. In many protocols, postoperative chemotherapy includes the administration of weekly vincristine (VCR) between induction chemotherapy cycles, regardless of scheduled AHPCC. We observed anecdotal AHPCC failures in children receiving midcycle VCR (MC-VCR).The study was an 8-year retrospective chart review of all children with a CNS malignancy and who underwent AHPCC. Information included patient demographic and clinical data, mobilization regimen, VCR administration, product yields, infusion toxicity, and patient charges. Data were analyzed relative to MC-VCR administration. Graphics and statistical analysis (t-test, chi-square, linear regression) were performed with commercial software.Twenty-four patients and 47 AHPCCs were available for analysis. Nine patients (37%) received MC-VCR within 7 days of scheduled AHPCC. MC-VCR was associated with delayed marrow recovery (17.9 days vs. 14.9 days, p=0.0012), decreased median peripheral CD34 counts (75 × 10(6) CD34/L vs. 352 × 10(6) CD34/L, p=0.03), decreased median CD34 yields (2.4 × 10(6) CD34/L vs. 17.8 × 10(6) CD34/kg, p=0.08), more AHPCCs per mobilization (2.9 vs. 1.1, p=0.01), and an increased rate of remobilization (33% vs. 6%). Mean patient charges were 2.5× higher in patients receiving MC-VCR than controls (p=0.01).MC-VCR should be withheld before scheduled AHPCC to optimize CD34 collection.

SUBMITTER: Cooling L

PROVIDER: S-EPMC4966665 | biostudies-other | 2014 Aug

REPOSITORIES: biostudies-other

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The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors.

Cooling Laura L Bombery Melissa M Hoffmann Sandra S Davenport Robertson R Robertson Patricia P Levine John E JE

Transfusion 20140217 8

<h4>Background</h4>Central nervous system (CNS) malignancies represent 20% of all childhood cancers. To improve outcomes in infants and children with high-risk disease, treatment can include adjuvant chemotherapy and early autologous peripheral blood human progenitor cell collection (AHPCC), followed by high-dose chemotherapy and stem cell rescue. In many protocols, postoperative chemotherapy includes the administration of weekly vincristine (VCR) between induction chemotherapy cycles, regardles ...[more]

PMID: 24527786

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Project description:BackgroundNucleotide-specific 5-hydroxymethylcytosine (5hmC) remains understudied in pediatric central nervous system (CNS) tumors. 5hmC is abundant in the brain, and alterations to 5hmC in adult CNS tumors have been reported. However, traditional approaches to measure DNA methylation do not distinguish between 5-methylcytosine (5mC) and its oxidized counterpart 5hmC, including those used to build CNS tumor DNA methylation classification systems. We measured 5hmC and 5mC epigenome-wide at nucleotide resolution in glioma, ependymoma, and embryonal tumors from children, as well as control pediatric brain tissues using tandem bisulfite and oxidative bisulfite treatments followed by hybridization to the Illumina Methylation EPIC Array that interrogates over 860,000 CpG loci.ResultsLinear mixed effects models adjusted for age and sex tested the CpG-specific differences in 5hmC between tumor and non-tumor samples, as well as between tumor subtypes. Results from model-based clustering of tumors was used to test the relation of cluster membership with patient survival through multivariable Cox proportional hazards regression. We also assessed the robustness of multiple epigenetic CNS tumor classification methods to 5mC-specific data in both pediatric and adult CNS tumors. Compared to non-tumor samples, tumors were hypohydroxymethylated across the epigenome and tumor 5hmC localized to regulatory elements crucial to cell identity, including transcription factor binding sites and super-enhancers. Differentially hydroxymethylated loci among tumor subtypes tended to be hypermethylated and disproportionally found in CTCF binding sites and genes related to posttranscriptional RNA regulation, such as DICER1. Model-based clustering results indicated that patients with low 5hmC patterns have poorer overall survival and increased risk of recurrence. Our results suggest 5mC-specific data from OxBS-treated samples impacts methylation-based tumor classification systems giving new opportunities for further refinement of classifiers for both pediatric and adult tumors.ConclusionsWe identified that 5hmC localizes to super-enhancers, and genes commonly implicated in pediatric CNS tumors were differentially hypohydroxymethylated. We demonstrated that distinguishing methylation and hydroxymethylation is critical in identifying tumor-related epigenetic changes. These results have implications for patient prognostication, considerations of epigenetic therapy in CNS tumors, and for emerging molecular neuropathology classification approaches.

Dataset Information

The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors.

Publications

The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors.

Similar Datasets

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