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Purpose: Majority of pediatric cancer patients are treated with chemotherapy using Venous Access Ports (VAP). However, after surgical removal of the VAP prominent scars often remain and standard care is lacking.Methods: Patients (N = 20) who were willing to participate were included prior to surgical removal of their VAP. All patients were off therapy at time of VAP removal. Patients had the option to either choose from Dermatix®, meridian color therapy (MCT), or no additional treatment (NAT). Assessment of scars was done prior to and 3, 6, and 12 months after surgical VAP removal using Patient and Observer Scar Assessment Scales (POSAS) questionnaires. To identify whether Dermatix® or MCT is associated with better scar healing than without additional treatment, Mann-Whitney U tests were used.Results: After 12 months of follow-up, both patients and dermatologists noted VAP scars had healed better after MCT compared to those without treatment (P = 0.010 for both POSAS patient and POSAS observer). No significant differences were observed between VAP scars after Dermatix® use and those with no treatment.Conclusions: Scar healing after MCT significantly improved, whereas Dermatix® treatment showed no significant differences compared to NAT. To translate this to daily care, a larger prospective study is needed to validate these findings. [ABSTRACT FROM AUTHOR]

In order to identify acute myeloid leukemia (AML) CD34+-specific gene expression profiles, mononuclear cells from AML patients (n=46) were sorted into CD34+ and CD34− subfractions, and genome-wide expression analysis was performed using Illumina BeadChip Arrays. AML CD34+ and CD34− gene expression was compared with a large group of normal CD34+ bone marrow (BM) cells (n=31). Unsupervised hierarchical clustering analysis showed that CD34+ AML samples belonged to a distinct cluster compared with normal BM and that in 61% of the cases the AML CD34+ transcriptome did not cluster together with the paired CD34− transcriptome. The top 50 of AML CD34+-specific genes was selected by comparing the AML CD34+ transcriptome with the AML CD34− and CD34+ normal BM transcriptomes. Interestingly, for three of these genes, that is, ankyrin repeat domain 28 (ANKRD28), guanine nucleotide binding protein, alpha 15 (GNA15) and UDP-glucose pyrophosphorylase 2 (UGP2), a high transcript level was associated with a significant poorer overall survival (OS) in two independent cohorts (n=163 and n=218) of normal karyotype AML. Importantly, the prognostic value of the continuous transcript levels of ANKRD28 (OS hazard ratio (HR): 1.32, P=0.008), GNA15 (OS HR: 1.22, P=0.033) and UGP2 (OS HR: 1.86, P=0.009) was shown to be independent from the well-known risk factors FLT3-ITD, NPM1c+ and CEBPA mutation status. [ABSTRACT FROM AUTHOR]

The article evaluates the diagnostic value of procalcitonin (PCT) in chemotherapy-related neutropenia and fever to investigate whether PCT can select a group of neutropenic patients with fever at low risk for bacteremia, which might be treated with oral antibiotics and discharged earlier. Blood for PCT, C-reactive protein, blood cultures and leukocyte count was taken directly at presentation with fever as well as cultures from other suspicious sites. This study included 66 consecutive febrile episodes experienced in 49 cancer patients with chemotherapy-related neutropenia.

Unlabelled: Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In AML cells, EphB1 transcript was inversely correlated with EphB1 promoter methylation. The presence of EphB1 allowed EfnB1 ligand-mediated p53 DNA binding, leading to restoration of the DNA damage response (DDR) cascade by the activation of ATR, Chk1, p53, p21, p38, CDK1(tyr15), and Bax, and downregulation of HSP27 and Bcl2. Comparatively, reintroduction of EphB1 expression in EphB1-methylated AML cells enhanced the same cascade of ATR, Chk1, p21, and CDK1(tyr15), which consequently enforced programmed cell death. Interestingly, in pediatric AML samples, EphB1 peptide phosphorylation and mRNA expression were actively suppressed as compared with normal bone marrow, and a significant percentage of the primary AML specimens had EphB1 promoter hypermethylation. Finally, EphB1 repression associated with a poor overall survival in pediatric AML. Combined, the contribution of EphB1 to the DDR system reveals a tumor-suppressor function for EphB1 in pediatric AML., Implications: The tumor-suppressor function of EphB1 is clinically relevant across many malignancies, suggesting that EphB1 is an important regulator of common cancer cell transforming pathways., (©2015 American Association for Cancer Research.)

Background: We report on the treatment of children and adolescents with acute lymphoblastic leukemia (ALL) in first relapse. The protocol focused on: (1) Intensive chemotherapy preceding allogeneic stem cell transplantation (SCT) in early bone marrow relapse; (2) Rotational chemotherapy in late relapse, without donor; (3) Postponement of cerebro-spinal irradiation in late isolated CNS relapse; and (4) Treatment in very late bone marrow relapse with chemotherapy only., Methods: From January 1999 until July 2006 all 158 Dutch pediatric patients with ALL in first relapse were recorded. Ninety-nine patients were eligible; 54 patients with early and 45 with late relapse. Eighteen patients had an isolated extra-medullary relapse; 69 patients had bone marrow involvement only., Results: Five-years EFS rates for early and late relapses were 12% and 35%, respectively. For early relapses 5 years EFSs were 25% for patients transplanted; 0% for non-transplanted patients. For late relapses 5 years EFS was 64% for patients treated with chemotherapy only, and 16% for transplanted patients. For very late relapses EFS was 58%., Conclusions: Our data suggest the superiority of SCT for early relapse patients. For late relapses a better outcome is achieved with chemotherapy only using the rotational chemotherapy scheme. The most important factor for survival was interval between first CR and occurrence of the first relapse., (Copyright © 2011 Wiley-Liss, Inc.)

Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by clonal malignant haematopoiesis with a differentiation arrest and excessive proliferation of leukaemic blasts. Over the past decades, the heterogeneity of AML has been illustrated by evolving classifications based on morphology (French-American-British classification (FAB classification), cytogenetic abnormalities (e.g. t(8;21), monosomies etc.), phenotype and÷or molecular abnormalities (e.g. Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD), mutations in nucleophosmin 1 (NPM1) and the transcription factor CCAAT ÷enhancer binding protein a (CEBPA), etc.). The current World Health Organisation (WHO) 2008 classification has integrated these classification modalities. Clinically, dissection of AML into various subtypes allows better survival prediction, but has still limited impact on treatment strategies, with the exception of all-trans retinoic acid treatment for AML-M3 and no allogeneic haematopoietic cell transplantation in complete remission (CR1) for patients with normal karyotype bearing an NPM1 mutation without FLT3-ITD. However, enhanced understanding of the molecular biology of AML will likely result in more 'tailor-made' therapies, for example by adding specific tyrosine kinase inhibitors to standard chemotherapy. In this review, we summarise the variables currently used to classify AML. Specifically, the contribution of microarrays in classification, prognosis and understanding of pathobiology of AML is discussed.

In AML high VEGFA protein expression correlates with poor overall and relapse-free survival (OS/RFS). To date, the relevance of the various VEGFA isoforms is unclear. We determined VEGF121, VEGF145, VEGF148, VEGF165, VEGF183, and VEGF189 mRNA expression in pediatric AML samples and investigated the relation between VEGFA isoform expression and clinicopatholologic characteristics and outcome. A significant co-expression of VEGF121, VEGF165, VEGF183, and VEGF189 isoforms was apparent (mean rho = 0.716, P < 0.0001). This co-expression justifies measuring a single VEGFA isoform (e.g., 121, 165, 183, and 189) as representative expression of all VEGFA isoforms in future studies designed to determine the prognostic importance of VEGFA isoforms.

In the past decades, a lot of effort has been put in identifying the role of matrix metalloproteinases (MMPs) in cancer. The main role of MMPs in angiogenesis, tumor growth and metastasis is degradation of extracellular matrix (ECM) and release and/or activation of growth factors through their degradative activity. The degradative activity finally results in cancer progression. MMP-inhibitors (MMPIs) have already been designed and tested, based on the degradative role of MMPs in cancer progression. First clinical trials with MMPIs have been performed with disappointing results, showing that in order to use MMP-inhibition the mechanisms underlying MMP-expression in cancer have to be further elucidated. This paper reviews the mechanisms of MMPs on molecular and cellular level and discusses the role for MMPs and MMP-inhibition in cancer with special focus on acute leukemia.

Cancer patients treated with chemotherapy are susceptible to bacterial infections. When an adult patient presents with febrile neutropenia, standard diagnostic care includes physical examination, laboratory diagnostics, chest X-ray (CXR) and sinus radiography. However, the yield of routine radiography in the diagnostic evaluation of ambulatory adult febrile neutropenic patients with normal findings at their physical examination is questionable. Two CXRs and one sinus X-ray were obtained in 109 and 106 febrile neutropenic episodes after chemotherapy in ambulatory adult patients who had no clinical signs suggesting pulmonary infection or sinusitis. We found that in only two of 109 (1.8%; 95% Confidence Interval (CI): 0.3-5.8%) febrile neutropenic episodes without clinical signs of new pulmonary disease, the CXR showed a consolidation suggesting pneumonia. In addition, in five of 88 (5.7%; 95% CI: 2.2-12.0%) febrile episodes in asymptomatic patients, sinus X-ray suggested sinusitis. In none of these seven episodes was a change of antibiotic therapy necessary. In the absence of clinical signs indicating pneumonia or sinusitis, the yield of CXR and sinus radiography in ambulatory adult cancer patients presenting with febrile neutropenia is minimal; CXR and sinus radiography should no longer be performed on a routine basis.