Preserved global histone H4 acetylation linked to ETV6-RUNX1 fusion and PAX5 deletions is associated with favorable outcome in pediatric B-cell progenitor acute lymphoblastic leukemia.

Epigenetic dysregulation is a hallmark of cancer executed by a number of complex processes the most important of which converge on DNA methylation and histone protein modifications. Epigenetic marks are potentially reversible and thus promising drug targets. In the setting of acute lymphoblastic leukemia (ALL) they have been associated with clinicopathological features including risk of relapse or molecular subgroups of the disease. Here, using immunocytochemistry of bone marrow smears from diagnosis, we studied global histone H4 acetylation, whose loss was previously linked to treatment failure in adults with ALL, in pediatric patients. We demonstrate that preserved global histone H4 acetylation is significantly associated with favorable outcome (RFS, EFS, OS) in children with B cell progenitor (BCP) ALL, recapitulating the findings from adult populations. Further, for the first time we demonstrate differential histone H4 acetylation in molecular subclasses of BCP-ALL including cases with ETV6-RUNX1 fusion gene or PAX5 deletion or deletions in genes linked to B cell development. We conclude global histone H4 acetylation is a prognostic marker and a potential therapeutic target in ALL.

Angiosarcoma in children - still uncontrollable oncological problem. The report of the Polish Paediatric Rare Tumours Study.

Angiosarcoma in children - still uncontrollable oncological problem. The report of the Polish Paediatric Rare Tumours StudyAngiosarcoma is a rare, highly malignant vascular neoplasm with little data available on its clinical course and management in children. Ten children with angiosarcoma (M/F: 6/4; aged 2, 3-16 years) registered in Polish Paediatric Rare Tumours and Soft Tissue Sarcomas Studies between 1992 and 2006. Primary tumour exceeded 5 cm in seven patients and affected mainly deep tissues (heart-2, head/neck, bladder, brain, liver and upper limb - one patient each). Four patients had regional and two metastatic diseases (lungs and bones). Three patients were initially misdiagnosed as haemangioma. Complete primary excision was unfeasible even in local stages. All patients received supplementing chemotherapy with no response in four. Radiotherapy was given to five children, including three after relapse. Three of five secondary tumour resections proved complete. Seven patients experienced relapses (mainly metastatic) and two continuous progression. Relapsed patients received chemotherapy +/- radiotherapy and surgery (three). Nine patients died of disease (overall survival 6-66 months), and one child after mutilating secondary resection is alive. Angiosarcoma in children is highly aggressive with an extremely poor prognosis. Complete primary excision is unfeasible, even in seemingly local stages. The response to chemotherapy is poor and the large number of metastatic recurrences suggests a need for systemic therapy modifications.

Late cardiotoxicity of anthracyclines in children with acute leukemia.

Congestive heart failure is one the most severe late complications of cancer therapy with anthracyclines. The function of the heart muscle was evaluated in 50 children (30 boys and 20 girls), aged from 5 years 6 months to 20 years 7 months, treated in the past for lymphoblastic or nonlymphoblastic acute leukemia. The total dose of the administrated anthracyclines was 120-550 mg/m2. The circulatory system was evaluated on the basis of history, physical examination, ECG, exercise test and echocardiography. Impaired contractility of the heart muscle was found in 32% of cases. The degree of impairment was related to the total dose of anthracyclines and to the period from discontinuation of therapy. Heart muscle function disorders were present also in children, in whom the cumulative dose of anthracycline antibiotics did not exceed 400 mg/m2. In the majority of patients the evidence of heart damage was subclinical.

[The assessment of hepatic enzymes' levels in children treated for leukemia and non-Hodgkin's lymphomas]. / Ocena poziomów enzymów watrobowych u dzieci leczonych z powodu bialaczek i chloniaków nieziarniczych.

The purpose of this study was to determine the frequent of serum aminotransferase elevation in children with leukemias and non-Hodgkin's lymphomas and define the cause of this pathology. In the serum of 43 children the bilirubin concentration, activities of aspartic aminotransferase (AspAT), alanine aminotransferase (AlAT) and gammaglutamylotranspeptidase (GGTP) were measured before treatment, during and after intensive chemotherapy. 43 patients 8 (65%) had bilirubin concentration above 1.2 mg/dl and/or aminotransferase activities above 100 U/l. The most possible causes of the liver damage in the patients were: hepatotoxicity of chemotherapy, virus or bacterial infections and leukemic or lymphomatous involvement of the liver.

[Cytoprotective effect of amifostine in children during induction therapy according to BFM-83: report on cases]. / Cytoprotekcyjny efekt amifostyny stosowanej u dzieci w czasie indukcji remisji wedlug programu BFM-83--opis przypadków.

Amifostine is the agent of proved cytoprotective activity against alkylating drugs and rubidomycine. Its protective effect against other cytotoxic drugs is doubtful. BFM-83 induction therapy for ANLL (ARA-C + RUB + VP-16) which is applied to children with acute non-lymphoblastic leukemia (ANLL) commonly contributes to severe adverse reactions. We administered amifostine to three children: 2 boys with ANLL (7 and 11 yrs) and 1 girl with MDS (3 yrs) during etoposide and rubidomycine induction therapy in order to decrease chemotherapy-related adverse reactions. Doses of amifostine were 740 mg/m2, 910 mg/m2 and 910 mg/m2 respectively. Efficacy of the therapy was evaluated on the base of blast decline in the bone marrow, efficacy of the cytoprotection by myelo and nephrotoxicity symptoms analysis. Chemotherapy-related adverse effects in the children protected by amifostine were less severe and observed by the shorter periods as compared with the historical control group of 20 patients treated according to BFM-83 without cytoprotection. These cases show the potential beneficial effect of amifostine during BFM-83 induction therapy for ANLL. The further randomised clinical study of the proposed cytoprotection should be performed to establish its value.

[Central venous lines in children with cancers]. / Centralne drogi dozylne w leczeniu dzieci z chorobami rozrostowymi.

Authors analyzed clinical aspects of central venous lines in children with cancer. In 25 patients central venous catheters with subcutaneous ports and in 34 patients lines with external ending were inserted. Catheters were left in place respectively 62-836 days and 4-365 days. During that time 10 catheters were removed due to occlusion, leakage, local infection or sepsis. The causes of these complications were analyzed in discussion.

[Prophylactic replacement therapy of hemophilia]. / Zapobiegawcze leczenie substytucyjne w hemofilii.

Medical care of patients with hemophilia A and B involves regular ambulatory check-ups and contemporary replacement therapy. The Institute of Pediatrics in Lódz--as other medical centres in several countries--prophylactically treats some hemophilic patients, usually once per 7-10 days, with infusions of absent coagulation factor. Such treatment was carried out in 10 boys with severe hemophilia A and B with marked clinical symptoms. An analysis of health prior to and during prophylactic therapy was carried out. Such an analysis has shown that such a treatment is beneficial due to the shortening of hospitalization, change in the character of hemorrhage and possibility of rehabilitation free from the risk of complications.