Hypovitaminosis D Influences the Clinical Presentation of Immune Thrombocytopenia in Children with Newly Diagnosed Disease.

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia defined as platelet count in peripheral blood <100 × 109/L. Hypovitaminosis D is very common in children with autoimmune diseases. To analyze whether hypovitaminosis D is associated with the clinical presentation of ITP in children, medical records of 45 pediatric patients with newly diagnosed immune thrombocytopenia in the coastal region of Croatia were evaluated. The severity of bleeding was assessed using two bleeding scores. Children with lower 25-hydroxyvitamin D (25(OH)D) values had higher values of the skin-mucosa-organ-gradation (SMOG) bleeding score and respectively more severe bleeding on diagnosis of ITP. With further analysis of the main domains of that score, we found that patients with a lower 25(OH)D value had more severe bleeding in the skin and organs. When 25(OH)D and ITP Bleeding Scale (IBLS) score were analyzed, a negative correlation was found, but it was not significant. Our findings suggest that hypovitaminosis D influences the severity of the clinical presentation of ITP in children on initial diagnosis of the disease. Therefore, therapy with 25(OH)D could be a new potential option for treatment of ITP. To investigate the connection between 25(OH)D and the incidence and severity of ITP, further studies, especially randomized controlled studies, are needed.

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.

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-1alpha, IL-2, IL-3, IL-4, IL-6, IL-10, TNF-alpha, IFN-alpha, and IFN-alpha 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-alpha 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-alpha, and higher level of IFN-alpha. 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-alpha--might be involved in the pathogenesis of newly diagnosed ITP. TNF-alpha is the most informative variable for discrimination between healthy children and those with ITP.

Relationship between previous maternal transfusions and haemolytic disease of the foetus and newborn mediated by non-RhD antibodies.

BACKGROUND: The aim of this study was to determine the relationship between non-RhD immunisation and the consequent development of haemolytic disease of the newborn in pregnant women with a history of red blood cell transfusion compared to those without a history of transfusion. MATERIALS AND METHODS: This retrospective cohort study included all pregnancies with red blood cell antibodies that were tested between 1993 and 2010. Data were obtained from the forms for immunisation tracking at the Department of Transfusion Medicine. Each form contained data on previous maternal transfusions, antibody specificities and whether the antibodies caused haemolytic disease of the newborn. RESULTS: Clinically significant non-RhD antibodies was found in 214 of 108,000 pregnancies, of which the most frequent were anti-E (n =55), anti-K (n =54), and anti-c (n =52) antibodies. A history of red blood cell transfusion was identified in 102 (48%) of the pregnancies in which non-RhD antibodies were found (in 78% of the anti-K cases, 40% of the anti-c and 18% of the anti-E cases). Non-RhD antibodies caused haemolytic disease of the newborn in 44 cases of which 14 were very severe (2 anti-K, 8 anti-c, 3 anti-Rh17, 1 anti-E). The mother had a positive history of red blood cell transfusion in 39% of the cases of haemolytic disease of the newborn. Anti-c antibodies were involved in all cases with severe haemolytic disease of the newborn and a history of maternal red blood cell transfusion. CONCLUSION: Primary prevention by using K-negative, Rhc-, RhE-, and RhC-compatible red blood cell transfusion for women younger than 45 years may prevent up to 40% of cases of haemolytic disease of the newborn. Rhc compatibile transfusion is the most important prevention strategy against severe haemolytic disease of the newborn caused by non-RhD antibodies.

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.

Rare localization of extrarenal nephroblastoma in 1-month-old female infant.

Extrarenal occurrence of Wilms' tumor is exceptional and the diagnosis is almost always made after surgery. The exact mechanism whereby a Wilms' tumor occurs in extrarenal tissue is unknown. The tumor is most commonly located in the retroperitoneum or inguinal region. Localization in subcutaneous tissue is extremely rare. In this paper, the case of a 1-month-old female infant with an extrarenal Wilms' tumor located in the lumbosacral region is presented. Surgical excision is the treatment of choice, and the same general therapeutic rules should be followed as when the kidney is affected.

Relationship between tumor vascularity and vascular endothelial growth factor as prognostic factors for patients with neuroblastoma.

Although the role of angiogenesis in tumor progression and response to treatment is generally well-characterized, for neuroblastomas clinical data regarding the contribution of angiogenesis and its predictive capacity remain unclear. The aim of this study was to evaluate whether tumor vascularity in the combination with expression of vascular endothelial growth factor (VEGF) represent prognostic factors for patients with neuroblastoma. Immunohistochemistry using anti-CD34 and anti-VEGF antibodies was used to analyze paraffin-embedded primary tumor tissues from 56 patients diagnosed with neuroblastoma. Tumor vascularity was estimated by calculating the tumor vascular volume fraction (TVVF), and VEGF expression was determined using semi-quantitative scoring. Statistical analyses including multivariate analysis were performed and compared with these two factors. Tumor vascularity had impact on survival of high VEGF expression neuroblastoma patients. Combination of high VEGF expression and TVVF value < or = 5% was independent predictor of overall survival (p-value = 0.0041, odds ratio (OR) (95% CI) = 8.67 (1.99-37.69) by the Cox proportional hazards model). This study revealed for the first time a group of extremely high-risk neuroblastoma with both high VEGF expression and poor vascularity. For these patients reduced rates of survival were observed (37% vs. 92.5%) (p < 0.0001). These patients did not experience a significant improvement following hematopoietic stem cell transplantation, and could be candidates for receiving novel therapies. These results indicate the importance of the mutual relationship between tumor vascularity and VEGF, because it gives better insight into the prognosis of patients with neuroblastoma.

Parental type of personality, negative affectivity and family stressful events in children with cancer.

OBJECTIVE: Psychological interactions between parents,children and social environment are very important for childhood health. The type of personality and stressful events are probably also cancer risk factors. We investigated personality types A/B and D (negative affectivity and social inhibition) in parents of children with cancer (PCC), as well as social environmental factors, and family / children's stressful events before the appearance of cancer. SUBJECTS AND METHODS: Bortner Type A Scale for evaluating parental type A/B personality, and 14 question personality test (DS14) for parental type D personality (negative affectivity and social inhibition score) were performed. Questionnaire eligible information about stressful events and social environmental factors in children with cancer (CC) were analyzed. RESULTS: Analyzing 127 PCC and 136 parents of healthy children (PHC) we found no significant differences in A/B type personality and social inhibition. There was significant difference in negative affectivity. PCC had more negative affectivity than PHC. We found more stressful events before cancer appearance in the families of children with cancer (FCC) than in healthy families (FHC), and more children's stressful events in CC then in healthy ones (HC). There were more quarrels in FCC, while CC were more "easy good-mannered children" than HC. CONCLUSIONS: Our results support the hypothesis that stress is a cancer risk factor and the idea that impaired parental functioning may be a mechanism linking family stress with the aetiology of cancer.

Familial hemophagocytic lymphohistiocytosis in a 6-week-old male infant.

Familial hemophagocytic lymphohistiocytosis (FLH) is an autosomal recessively inherited multisystem disease. This defect in cellular cytotoxicity is a life threatening condition characterized by fever, rash, splenomegaly, cytopenias and neurologic manifestations. PRF1, UNC13D and STX11 gene defects underlie in about 40-50% of primary cases. Chemoimmunotherapy followed by hematopoietic stem cell transplantation improved disease outcome. We report a case of a 6-week-old boy who presented with a fever, diffuse rash, disseminated intravascular coagulation, hypofibrinogenemia, hypertrigliceridemia, hepatosplenomegaly, leukocytosis with 90% of lymphocytes, granulocytopenia, anemia, trombocytopenia, hyperferritinemia and pathological findings in cerebrospinal fluid. The patient had decreased frequency of NK cells and low NK cell activity in peripheral blood. Bone marrow aspiration analysis showed degenerative changes of histocyte cells, with preserved cytophages (lymphophages and erythrophages) consistent with hematophagocytic syndrome. Given that the molecular diagnosis of the known mutations in genes PRF1 and UNC13D showed a mutation in UNC13D, the diagnosis of familial hemophagocytic lymphohistiocytosis subtype 3 was established. HLH-2004 chemotherapy protocol was performed and partial remission with residual central nervous system disease was achieved. Hematopoietic stem cell transplantation was successfully performed with an unrelated HLA-matched donor. Familiar HLH is generally a progressive and fatal disease. Early diagnosis with molecular genetic analysis and chemoimmunotherapy followed by hematopoietic stem-cell transplantation is the best approach.

Expression and prognostic value of the Ki-67 in Wilms' tumor: experience with 48 cases.

PURPOSE: Ki-67, tumor proliferation marker, is an important prognostic factor in a variety of cancers. In the present study, we investigated the expression and the prognostic value of Ki-67 in nephroblastoma. METHODS: Ki-67 expressions were investigated by immunohistochemistry on paraffin-embedded material in 48 children operated on because of nephroblastoma. Patients were treated according to SIOP protocol. The mean follow-up period was 5.4 years. A proliferation index was obtained by immunohistochemistry using anti-Ki-67 anti-body. RESULTS: The mean Ki-67 proliferation index in the blastemal type was 12.3%, and in the epithelial type, 21.4%. In the anaplastic type, Ki-67 proliferation index was: in the blastemal component 20%, in the stromal 21%, and in the epithelial 31%. In the mixed tumor type, Ki-67 proliferation index was assessed as: in the blastemal component 10%, in the epithelial 33% and in the stromal 31.5%. Proliferation index for the epithelium was significantly higher than those found for the blastema (P = 0.001). A correlation between Ki-67 and tumor stage found proliferation index significantly higher in stages I and II (P = 0.002). CONCLUSION: The results support the conclusion that Ki-67 is a relevant marker for assessing the proliferative activity and tumor cell dynamics of nephroblastoma, but it may not be a good clinical prognostic marker.

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.

Anti-CD20 monoclonal antibody (rituximab) for therapy of CD20-positive nodular lymphocyte-predominant Hodgkin lymphoma in an 10-year-old girl.

Biologic treatments including antibody-based therapies are still in early-phase development in Hodgkin lymphoma. The authors present the case of a 10-year-old girl with massive, solid, unilateral cervical, nodular lymphocyte-predominant Hodgkin lymphoma. Chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]) and radiotherapy were given, according to the Italian Association of Pediatric Hematology and Oncology (AIEOP) MH-96 study protocol, but the patient failed to enter complete remission. Soon after, 6 intravenous infusions of the chimeric anti-CD20 monoclonal antibody rituximab 375 mg/m2 were administered, resulting in complete remission. The patients is still in continuous complete remission for 2 years. Novel therapies, such as rituximab, may be useful for children with CD20+ nodular lymphocyte-predominant Hodgkin lymphoma. To the authors' knowledge, this is the first report of CD20+ nodular lymphocyte-predominant Hodgkin lymphoma treated with rituximab in children. Further controlled trials and long-term outcome studies are warranted to define its clinical application and to improve the care of patients.

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.