Srđana Čulić

Immune thrombocytopenia: serum cytokine levels in children and adults

Background Immune thrombocytopenia (ITP) is an immune-mediated platelet disorder in which autoantibody-coated platelets are removed from the blood by monocytic phagocytes and there is impaired platelet production. There is a delicate balance of specific cytokine levels, which has an important role in the immune system and is known to be deregulated in autoimmune diseases. This study was designed to investigate the differences in Th cytokine levels between children and adults with newly diagnosed ITP and to compare these profiles to those found in healthy, age-matched controls. Material/Methods The concentration of IL-1α, IL-2, IL-3, IL-4, IL-6, IL-10, TNF-α, IFN-α, and IFN-γ in serum specimens was analyzed by enzyme-linked immunosorbent assay. Results At the time of ITP diagnosis, children showed significantly lower serum levels of interleukin IL-2 and tumor necrosis factor TNF-α and higher serum level of IL-3 than healthy controls. Serum level of IL-4 in adult ITP patients was higher than those in control subjects. When compared with adults, children with ITP had lower serum level of IL-4, IL-6 and IFN-γ, and higher level of IFN-α. Conclusions Significant differences in serum cytokine levels between pediatric patients and healthy controls indicate that cytokine disturbances – especially changes in IL-2, IL-3 and TNF-α – might be involved in the pathogenesis of newly diagnosed ITP. TNF-α is the most informative variable for discrimination between healthy children and those with ITP.

Vascular endothelial growth factor in children with neuroblastoma: a retrospective analysis

BackgroundDespite aggressive therapy, advanced stage neuroblastoma patients have poor survival rates. Although angiogenesis correlates with advanced tumour stage and plays an important role in determining the tumour response to treatment in general, clinical data are still insufficient, and more clinical evaluations are needed to draw conclusions. The aim of this study was to evaluate vascular endothelial growth factor (VEGF) expression in patients with neuroblastoma, determine whether it correlates with other prognostic factors and/or therapeutic response, and to assess should VEGF be considered in a routine diagnostic workup.Materials and methodsVEGF expression was determined by immunohistochemistry using anti-VEGF antibody in paraffin embedded primary tumour tissue from 56 neuroblastoma patients. Semiquantitative expression of VEGF was estimated and compared with gender, age, histology, disease stage, therapy, and survival. Statistical analyses, including multivariate analysis, were performed.ResultsVEGF expression correlated with disease stage and survival in neuroblastoma patients. Combination of VEGF expression and disease stage as a single prognostic value for survival (P-value = 0.0034; odds ratio (OR) (95%CI) = 26.17 (2.97-230.27) exhibited greater correlation with survival than individually. Hematopoietic stem cell transplantation significantly improved survival of the advanced stage patients with high VEGF expression.ConclusionVEGF expression should be considered in a routine diagnostic workup of children with neuroblastoma, especially in those more than 18 months old and with advanced disease stage. High VEGF expression at the time of disease diagnosis is a bad risk prognostic factor, and can be used to characterize subsets of patients with an unfavourable outcome.

Correlations among age, cytokines, lymphocyte subtypes, and platelet counts in autoimmune thrombocytopenic purpura

While autoimmune thrombocytopenic purpura is mediated by autoantibodies, accumulating evidence suggests that T helper cells and the cytokines they produce also play a key role. We determined correlations among age, serum cytokine concentrations, circulating lymphocyte, and platelet counts in adult (n = 19) and children (n = 29) with autoimmune thrombocytopenic purpura. Correlations between age and cytokine levels were also assessed in healthy controls (n = 50). Significant positive correlations between age and serum levels of interferon‐gamma, age and CD4+ lymphocytes, age and natural killer cell count were observed in these patients. Absolute lymphocyte and CD8+ cell count was significantly inversely correlated with age. In adult patients, a significant inverse correlation between platelet and absolute lymphocyte count was observed. In pediatric patients, an inverse correlation of platelet count with serum concentration of interleukin‐3 was recorded. In 50 healthy volunteers there were significant positive correlations between age and interleukin‐3, ‐4, ‐6, and interferon‐gamma, and significantly negative correlations with interleukin‐2, tumor necrosis factor‐alpha, and interferon‐alpha. Additional evaluations are necessary to identify the impact of age‐related changes in immune function on the clinical course of autoimmune thrombocytopenic purpura. Pediatr Blood Cancer 2006;47:671–674.

Successful management of bleeding with recombinant factor VIIa (NovoSeven®) in a patient with Burkitt lymphoma and thrombosis of the left femoral and left common iliac veins

We present the case of an 18‐year‐old female with Burkitt lymphoma involving the intra‐abdominal and inguinal lymph nodes. The tumor had invaded the left femoral and common iliac veins causing secondary thrombosis and vessel occlusion. Chemotherapy and anticoagulant treatment resulted in mild thrombocytopenia and a prolonged prothrombin time, respectively, which exacerbated postoperative bleeding following surgical removal of a deep inguinal necrosis. After 6 days, bleeding combined with epistaxis was considered to be life threatening and anticoagulant reversal with recombinant factor VIIa was successfully performed. The patient has since achieved complete remission and subsequent antithrombotic therapy has resolved the vascular occlusion. Pediatr Blood Cancer 2007;49:332–335.

Endobronchial ALK+ anaplastic large-cell lymphoma resembling asthma in a 13-year-old girl.

Anaplastic large-cell lymphoma is a rare disease in children, and endobronchial localization is extremely rare in any age group. We report the case of a 13-year-old girl with endobronchial anaplastic lymphoma kinase–positive anaplastic large-cell lymphoma presenting as asthma, and discuss the diagnostic, therapeutic, and clinical implications.

Serum vitamin D levels in children with newly diagnosed and chronic immune thrombocytopenia

The primary objective of the study was to assess the vitamin D (VD) status of patients suffering from ITP. Children from the case cohort (total 21) were recruited from chronic ITP patients (followed as outpatients) and newly diagnosed ITP (prospective study) patients. VD deficiency (values <75 nmol/L) was detected in 11 patients with newly diagnosed ITP, and seven patients with chronic ITP. Only three patients with newly diagnosed, and none with chronic ITP had normal VD values. Newly diagnosed ITP patients had statistically significantly higher values (P <.044) of VD than the patients with chronic type of ITP. Platelets values did not follow VD level. VD deficiency is very common in children with either newly diagnosed or chronic ITP form. Therefore there is a utility supplementing VD in these patients. To investigate the role of VD as an immune modulating drug for patients with ITP, a prospective randomized placebo-controlled trial needs to be performed.

THROMBOCYTOPENIA AFTER BACILLE CALMETTE-GUÉRIN IMMUNIZATION—POSSIBLY ON AN IMMUNE BASIS

Pediatric Hematology and Oncology Incorporating the International Journal of Pediatric Hematology/Oncology Publication details, including instructions for authors and subscription information: http://www.informaworld.com/smpp/title~content=t713610311 THROMBOCYTOPENIA AFTER BACILLE CALMETTE-GUERIN IMMUNIZATION POSSIBLY ON AN IMMUNE BASIS Gordana Jakovljevic a; Srđana Culic b a Department of Hematology-Oncology, Pediatric Clinic, Childrens Hospital Zagreb, Zagreb, Croatia b Department of Pediatric Hematology, Oncology, Immunology and Medical Genetics, Pediatric Clinic, Clinical Hospital Split, Split, Croatia