[Treatment Refusal in Pediatric Oncology]. / Odmietnutie liecby v detskej onkológii.

BACKGROUND: Pediatric oncologists are often faced with situations in which parents or guardians refuse recommended treatment for curable childhood cancer. Deciding how to proceed in such situations is an ethical dilemma. The aim of this article is to consider optimal approaches when parents are strongly against oncological treatment, potentially compromising their childrens rights for health care and to the chance for cure. CASES: In this paper, we report two cases of treatment refusal from our department and the impact of such decisions on the children themselves. Case no. 1 describes a child with retinoblastoma whose parents refused standard treatment in order to seek alternative treatment abroad. Case no. 2 describes a patient with a primary lymphoma of bone who received treatment by a court order after parental refusal. CONCLUSION: When parents refuse a treatment for potentially curable cancer, the medical team often focuses on the certainty of death without treatment. In the background, there is a smaller but still significant risk that - even if the treatment is eventually accepted or compelled - the child will still die from treatment-related complications or refractory disease, possibly with considerable suffering. The reasons for refusing a treatment vary. The entire medical team is tasked with trying to respectfully understand the reasoning behind the parents unwillingness to accept the treatment, in order to address all possible misunderstandings and to propose solutions that could be acceptable for the parents. In some situations however, it is necessary to resolve the dilemma by legal means in order to protect the life of the child.Key words: oncology - ethics - decision making - treatment refusal - legal guardians The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 8. 2017Accepted: 7. 9. 2017.

Constitutive 53BP1/γH2AX foci are increased in cells of ALL patients dependent on BCR-ABL and TEL-AML1 preleukemic gene fusions.

Childhood leukemia arises from hematopoietic stem cells by induction of mutations. Quite often chromosomal translocations arise prenatally as first key event in multistage process of leukemogenesis. These translocations result in so called preleukemic gene fusions (PGFs), such as BCR-ABL and TEL-AML1, which generate hybrid proteins with altered properties. Critical DNA damage resulting in translocations are DNA double-strand breaks (DSBs). BCR-ABL and TEL-AML1 were shown to be associated with increased constitutive DSBs in various model systems. We analyzed cells from peripheral blood and CD34-/CD34+ cells from bone marrow of pediatric acute lymphoblastic leukemia (ALL) patients harboring BCR-ABL or TEL-AML1. We used sensitive technique that is based on automated enumeration of DSB co-localizing proteins γH2AX and 53BP1, which form so called DNA repair foci. We found that level of constitutive γH2AX/53BP1 foci is significantly higher in cells of ALL pediatric patients than in healthy subjects. There was also significant increased level of constitutive γH2AX/53BP1 foci in cells from ALL patients harboring BCR-ABL or TEL-AML1 compared to patients without PGFs. The same increase was observed regardless cell type for both PGFs. Our data on increased DSB levels in the BCR-ABL/TEL-AML1 patient's cells support a model where BCR-ABL/TEL-AML1 induces DNA instability through facilitating mutagenesis and appearance of additional genetic alterations driving leukemogenesis.

Combined multiplex and monoplex RT-PCR as a reliable and cost-effective method for molecular diagnostics of pediatric acute lymphoblastic leukemia.

The precise diagnosis of acute lymphoblastic leukemia is essential for correct prognosis assessment and therapy regimen selection. At present, immunophenotyping, cytogenetics and molecular screening are major and complementary methods utilized in a routine leukemia diagnostics. The aim of this study was to validate the application of multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay for molecular diagnosis of the most common pediatric acute lymphoblastic leukemia-associated fusion transcripts. Our data show that screening of bone marrow and/or peripheral blood by RT-PCR, consisting of multiplex and monoplex PCR, confirmed results of real-time quantitative PCR (RT qPCR). This screening may provide a reliable, specific and sensitive method amenable to standard laboratory practice and a cost-effective alternative to more complex and expensive RT qPCR techniques.

Minimal residual disease detection using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the non-MRD-based ALL IC-BFM 2002 protocol for childhood ALL: Slovak experience.

Acute lymphoblastic leukemia is the most common form of cancer in children. The 10-year event-free survival ranged from 77 to 85% after having achieved complete remission rates of 93% or higher. The main cause of treatment failure is relapse arising from outgrowth of residual leukemic cells that are refractory to therapy. An intense effort has been made to develop methods to determine the degree of minimal residual leukemia cells present in patients considered to be in morphological remission. Because of the strong correlation between minimal residual disease (MRD) levels and risk of relapse, monitoring of MRD provides unique information regarding treatment response. The MRD monitoring based on real-time quantitative PCR detection of patient-specific immunoglobulin and T-cell receptor (Ig/TCR) gene rearrangements is currently considered to be the most reliable tool for MRD-based diagnosis in ALL. Because the significance of MRD monitoring has been strongly supported by several studies and because it has been implemented in the latest protocols, there has been a significant effort to develop MRD monitoring in the Slovak Republic since 2005. Between October 2006 and December 2009, 50 children with ALL who were treated at three Slovak centers were included in the RQ PCR MRD pilot project. A total of 40 patients with BCP-ALL ( B cell precursor ALL) and 4 patients with T ALL were analyzed for Ig/TCR rearrangement. We identified 106 different rearrangements in the 44 ALL patients analyzed. Based on MRD stratification, we identified 26 patients who were stratified into the HRG ( high risk group) (n = 3; 11.5%), IRG ( intermediate risk group) (n = 14; 54%) and SRG ) standard risk group) (n = 9; 34.5%). Morphology-based risk stratification allows the identification of most HRG patients identified also by MRD-based stratification, but fails to discriminate the IRG assigned to therapy reduction. Patients in the SRG and the IRG could profit from MRD-based risk assignment

Systemic malignancies presenting as primary osteolytic lesion.

The tumor formation may be the earliest manifestation preceeding other symptoms, signs and bone marrow evidence of systemic malignancy - leukemia/lymphoma. Here we present three cases of systemic malignancy in which bone lesions were the first manifested signs of the disease. All three cases were thought to be orthopedic cases and had been treated as so without genuing improvement. We would like to draw an attention to children who present with multifocal musculoskeletal pain and the importance of whole-body scaning. We describe interesting cases of diffuse large cell lymphoma and leukemia that initially presented as primary osteolytic bone lesion and discuss the differential diagnosis, literature review of non-Hodgkin's lymphoma arising in bone as the primary site (Tab. 1, Fig. 3, Ref. 18). Full Text (Free, PDF) www.bmj.sk.

Our experience with tumor lysis syndrome treatment.

Tumor lysis syndrome (TLS) is caused by rapid tumor cell turnover resulting in a release of intracellular contents into the circulation, and subsequent numerous metabolic derangements (hyperkalemia, hypocalcemia, hyperphosphatemia, hyperuricemia). More than 90% of cases have laboratory manifestations, and only about 10% have clinical manifestations. The main complications are acute renal failure, cardiac arrhythmia and metabolic acidosis. The management of TLS consists of preventive measures in high-risk patients prior to cancer treatment as well as prompt initiation of supportive care for patients who develop acute tumor lysis syndrome during treatment. The traditional management consists of intravenous hydratation, urinary alkalinization, diuretics and control of hyperuricemia, electrolyte disturbances and dialysis if needed. The use of a new hypouricemic agent (rasburicase) in patients with TLS minimized the need for renal dialysis as well as reduced the incidence of complications seen in hyperproduction of uric acid to minimum (Tab. 4, Ref. 8). Full Text (Free, PDF) www.bmj.sk.

The state of research into children with cancer across Europe: new policies for a new decade.

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.