Regular exercise improves the well-being of parents of children with cancer.

AIM: Parents of children with cancer describe impaired physical and social functioning, sleep disturbance and poor mental health. Exercise-related interventions impact positively on these quality of life domains, but have not been examined in this population. The aim of this longitudinal pilot study was to explore the feasibility of a 12-week pedometer-monitored walking intervention among parents of children with cancer, assessing adherence to a set activity target of 70,000 steps per week, and to explore the benefits of physical activity on mental and physical health. METHODS: Parents were provided with a pedometer and requested to achieve a daily step count of 10,000 steps per day for 12 weeks. Mood, well-being and psychological distress were examined using validated questionnaires (Profile of Mood States 2nd edition [POMS-2], Distress Thermometer for Parents [DT-P] and Depression Anxiety Stress Scales [DASS-42]) at baseline, midpoint (6 weeks) and endpoint (12 weeks) to identify changes in these domains with increased activity. RESULTS: Fifteen parents were recruited. The majority increased their counts during the first 4 weeks of the study and maintained this to week 8 (n = 12). Time-dependent improvements were identified in the following psychometric test outcomes at week 12: DT-P score (likelihood ratio test [LRT] P = 0.02), POMS-2 total mood disturbance (LRT P = 0.03), fatigue inertia (LRT P = 0.009), tension anxiety (LRT P = 0.007) and vigour activity (LRT P = 0.001). CONCLUSIONS: Mental health benefits of a pedometer-based exercise intervention for parents of children with cancer were identified. Such programs should be included in a holistic approach to improve the psychological outcomes of parents whose children are receiving treatment for cancer.

Parents know best: or do they? Treatment refusals in paediatric oncology.

Although treatment refusal is an infrequent occurrence in paediatric oncology, it is an important issue that threatens the ongoing therapeutic relationship between the health-care team and families. While there are good reasons to support the decision-making authority of parents in the medical setting, parents' rights in this respect are not absolute. Fortunately, most disagreements between clinicians and parents regarding treatment decisions for children are resolved within the health-care team/family dyad or with the objective advice of other clinicians or clinical ethics services. The increasing appeal of 'natural therapies' and unsubstantiated confidence with which they are prescribed may lead to more frequent refusal of conventional, evidence-based oncology treatment in the future. The harm principle may assist paediatric oncologists in the difficult task of determining when it is justifiable to refer a case for judicial intervention.

HLA-DM expression is elevated in ETV6-AML1 translocation-positive pediatric acute lymphoblastic leukemia.

MHC Class II antigen processing and presentation to CD4+ T cells is important in anti-tumor immunity. ETV6-AML1-positive precursor-B acute lymphoblastic leukemia (pre-B ALL) is associated with good outcome and late relapse. We analyzed HLA-DR and the MHC Class II processing components HLA-DO, HLA-DM, and Class II-associated invariant chain peptide (CLIP) expression, in ETV6-AML1-positive and ETV6-AML1-negative ALL. Overall, CLIP expression was low, while HLA-DM was significantly higher in ETV6-AML1-positive cells. No significant difference in HLA-DO was observed. The HLA-DR(high)/CLIP(low)/HLA-DM(high) phenotype strongly suggests that ETV6-AML1 leukemia will induce favorable immune responses and may in part explain the characteristic late relapses associated with ETV6-AML1 pre-B ALL.

Opsoclonus-Myoclonus Syndrome, Neuroblastoma, and Insulin-Dependent Diabetes Mellitus in a Child: A Unique Patient.

AIM: We present a new and unique association of opsoclonus-myoclonus-ataxia syndrome with neuroblastoma and type 1 diabetes mellitus. PATIENT DESCRIPTION: This 17-month-old child presented with opsoclonus-myoclonus-ataxia syndrome. Investigations revealed a thoracic neuroblastoma. Eleven days later, she re-presented with diabetic ketoacidosis. The neuroblastoma was resected, and she was given immunotherapy. At 12 months' follow-up, her neurological signs and symptoms have significantly improved, but she continues to be insulin dependent. DISCUSSION: This child expands the clinical spectrum of autoimmune disorders associated with opsoclonus-myoclonus-ataxia syndrome.

Altered patterns of T cell cytokine production induced by relapsed pre-B ALL cells.

Relapse of pediatric acute lymphoblastic leukemia (ALL) remains a significant clinical problem. The graft-versus-leukemia (GVL) effect after hematopoietic stem cell transplantation indicates that immune mechanisms may play a role in the control of ALL blasts. In this study, we analyzed primary diagnostic and relapsed pre-B ALL samples for the surface expression of several molecules implicated in immune responses and for the induction of allogeneic T cell responses. There were no significant differences in the expression of CD11a, CD40, CD80 and CD86 or MHC classes I and II molecules between the diagnostic and relapsed samples. We found no significant differences in the overall ability of diagnostic and relapsed pre-B ALL samples to induce T cell proliferation and cytokine production. However, in the case of T cell responses induced by diagnostic ALL samples, there was excellent correlation between proliferation and production of all cytokines analyzed. In the case of relapsed samples, the only correlation obtained was with IL-5. This observation indicates that the nature of the immune response generated by relapsed ALL cells in an allogeneic setting differs from that obtained with diagnostic samples, suggests a biasing towards a Th2 response may contribute to the evasion of effective immune responses by relapsed ALL.

Infant anaplastic large cell lymphoma with hemophagocytic syndrome.

Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive, is uncommon in infancy. We present an unusual occurrence of infant ALCL, ALK-positive, associated with hemophagocytic syndrome. To the best of our knowledge, there have been no cases of infant ALCL, ALK-positive, described that have been associated with hemophagocytic syndrome. Particularly in this age group, primary hemophagocytic syndrome is also a consideration, which raises particular differential diagnostic considerations.

A population-based study of pediatric anaplastic large cell lymphoma.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is a relatively rare form of non-Hodgkin lymphoma (NHL) in children constituting 10-15% of this entity. To the authors' knowledge, there are no population-based pediatric studies in the literature, and incidence estimates have not been attempted. METHODS: A population-based study of all children in British Columbia, Canada, younger than 15 years of age presenting between January 1988 and December 1999 with an immunohistologically confirmed diagnosis of CD30+ ALCL was completed. Demographic, ethnic, clinical, treatment, and outcome details were collected on all patients. Population figures were obtained from census data through the BC STATS. RESULTS: Ten patients were identified and confirmed to have ALCL on the basis of morphology and immunohistochemical stains. This equates to an annual incidence of 1.2 per million children younger than 15 years of age. The mean age at diagnosis was 8.23 years with a range of 1.4-13.0 years. There was an overrepresentation of East and Southeast Asian patients (40%) in the ALCL group compared with other subtypes of NHL and the pediatric population of British Columbia. Twenty percent of the patients had evidence of central nervous system (CNS) disease at diagnosis. CONCLUSIONS: The annual incidence of ALCL in children younger than 15 years of age in British Columbia is 1.2 per million. The overrepresentation of East and Southeast Asian ethnic origin remains unexplained. The rate of CNS involvement is much higher than that previously reported in large non-population-based series (0-3%). Although the low numbers do not allow firm conclusions, it would seem prudent to continue to investigate all newly diagnosed patients for CNS involvement in British Columbia.

ETV6 (TEL)-AML1 pre-B acute lymphoblastic leukaemia cells are associated with a distinct antigen-presenting phenotype.

The recently recognized translocation t(12;21)(p13;q22), which results in the ETV6-AML1 fusion product, is the most common genetic rearrangement found in childhood pre-B acute lymphoblastic leukaemia (ALL). It has been associated with a more favourable prognosis and a distinct immunophenotype in terms of myeloid and B cell-associated antigen expression. Using flow cytometry, we investigated whether the unique ETV6-AML1 phenotype extended to molecules associated with antigen presentation by analysing 50 diagnostic bone marrow samples from paediatric pre-B ALL patients. Reverse transcription polymerase chain reaction for the ETV6-AML1 fusion transcript was positive in 14 patients. ETV6-AML1-positive samples were characterized by a significantly higher expression of the co-stimulatory molecule CD40 (P < 0.0001), as well as a significantly higher class II HLA-DR mean channel fluorescence (P = 0.001). In contrast, CD86 expression was significantly lower on fusion-positive samples (P = 0.010) while there was no difference in expression of CD80 or major histocompatibility complex class I between ETV6-AML1-positive and -negative samples. This is the first observation in acute leukaemia that the distinct immunophenotype associated with specific translocations includes the expression of molecules associated with antigen presentation. In the case of ETV6-AML1 pre-B ALL, this characteristic immunophenotype may have implications for the immunogenicity of the leukaemic cells.