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BACKGROUND The nucleosomal histone protein H2AX is specifically phosphorylated (γ-H2AX) adjacent to DNA double-strand breaks (DSBs) and is used for quantifying DSBs. Many chemotherapies and ionizing radiation (IR) used in cancer treatment result in DSBs. Therefore, γ-H2AX has a significant potential as a biomarker in evaluating patient sensitivity and responsiveness to IR and chemotherapy. METHODS Here, we report a flow cytometry-based quantification of γ-H2AX (FCM-γ-H2AX assay) customized for clinical practice. RESULTS We validated that our method is able to detect DNA damage in peripheral blood mononuclear cells (PBMCs) treated with DSB inducing agents. The method also detected the DNA repair deficiency in PBMCs treated with DNA repair inhibitors, as well as the deficiency in DNA repair signaling in PBMCs from two ataxia telangiectasia patients. CONCLUSIONS The FCM-γ-H2AX assay has sufficient analytical sensitivity and precision to measure levels of DNA damage and DNA repair for clinical purposes. © 2016 International Clinical Cytometry Society.

Background. Immunoreconstitution following childhood acute lymphoblastic leukemia (ALL) is a complex process during which various immune functions recover differentially. This process is difficult to elucidate since variables are interrelated and require simultaneous evaluation, rendering conventional statistical methods inappropriate. Procedure. We used principal components analysis (PCA) and projection of latent structures (PLS) to evaluate immune competence in 32 children treated for ALL. One or 6 months after completion of therapy, the relation between lymphocyte subpopulations, lymphocyte function and response to vaccination with tetanus, diphtheria and hemophilus influenzae, was investigated. Results. PCA demonstrated that increasing treatment intensity correlated with progressive immune dysfunction. Children treated with

Aim: Solid tumours constitute 40% of childhood malignancies. The Swedish Childhood Cancer Registry is population based and includes all children with cancer reported from the six paediatric oncolo ...

Objective The aim was to examine the immune reconstitution after current chemotherapy for childhood ALL, with a special focus on finding immunologic variables that predict a poor immune response to vaccinations. Procedure In a cross-sectional study of 31 children after treatment with the NOPHO ALL-1992 protocol peripheral blood lymphocyte subsets, T- and B-cell function in vitro and serum immunoglobulins (Ig) were measured. All patients were examined once, at 1 or at 6 months after cessation of chemotherapy, immediately before vaccination with DT and Hib. Results Lymphocytes, T-cells, and CD4+ T-cells were low at 6 months after treatment. Naive T-cell subsets were more reduced than memory subsets. In the high risk (HR) ALL group, CD8+ T-cells were reduced at 6 months. NK-cells were low at 1 month, but normal at 6 months; however, the CD3+CD56+ (NKT) subset was reduced at both time points. Total B-cell number was low at 1 month, but normal at 6 months. A relative increase of CD5+ B-cells (B-1 cells) was evident, particularly in the HR group. Antigen-independent T- and B-cell function in vitro were affected at 1 month, but virtually normalized at 6 months. Serum IgM level was decreased at 1 month and IgG3 level was increased at 1 and 6 months. Conclusions This study shows that immune reconstitution after childhood ALL is slower than previously reported and emphasizes the influence of treatment intensity. The most intensively treated patients still have persistent abnormalities in T-, B-, and NK-cell subsets at 6 months post therapy and show a poor response to immunization with T-cell dependent antigens. In the HR group, routine re-immunizations before this time point are of limited benefit, and the effect of repeated vaccinations should be evaluated. © 2004 Wiley-Liss, Inc.

UNLABELLED This study examined whether the initial plasma levels of tumour necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) in 131 children with newly diagnosed cancer were associated with haematopoietic suppression, and whether plasma levels of TNFalpha or haemoglobin at diagnosis affects long-term prognosis in childhood acute lymphoblastic leukaemia (ALL). CONCLUSIONS IFNgamma, and possibly also TNFalpha, were related to anaemia in children with solid tumours. Neither TNFalpha levels nor Hb levels were associated with increased risk of ALL relapse.

Chng (2003) indicated fever as an important part of the cytarabine syndrome and suggests cytokines as mediators. In an attempt to investigate the mechanisms behind cytarabine-induced fever, we evaluated 16 children (1AE5– 14AE8 years old) in clinical remission during high–dose cytarabine treatment (six infusions of 2 g/m 2 every 12 h). Fever (median 38AE5� C, range 38AE0–39AE7� C) occurred in 13 of 16 patients at a median of 28 h (20–47 h) after the start of the first infusion. The fever declined spontaneously in 10 of 13 patients despite continued infusions. The series of infusions was not interrupted in any case. Some patients showed signs of malaise, abdominal pain, myalgias and self-limiting rash, but none was severely ill. Blood cultures were negative and no antibiotics were administered. C-reactive protein was low at the beginning of treatment, but increased at 36 h to 21AE 5+6 AE6 mg/l [mean + standard error of the mean (SEM); P