Angela J. Alessandri

Age is the major determinant of recurrence in pediatric differentiated thyroid carcinoma

BACKGROUND A relationship between young age and increased risk of recurrence of pediatric differentiated thyroid carcinoma has been suggested; however, no attempts have been made to assess the prognostic factors or efficacy of treatment in very young children with this malignancy. The objectives of this study were to evaluate the association of age with outcome in pediatric differentiated thyroid carcinoma and to compare the clinical, pathologic, prognostic, and treatment variables between younger and older children with this disease. PROCEDURE A retrospective review of all patients presenting to the British Columbias Childrens Hospital or British Columbia Cancer Agency <17 years of age at diagnosis with differentiated thyroid carcinoma between January, 1955, and December, 1996, was completed. RESULTS Thirty-eight patients were identified, 12 of whom were </=10 years of age. The overall and relapse-free survivals at 20 years were 100% and 32.2%, respectively. Age at diagnosis was the only determinant of time to recurrence on univariate and multivariate regression analysis of prognostic factors (P = 0.022). The 20 year relapse-free survival for children < or =10 years of age was 10.1% vs. 48.3% for children >10 years. An association between young age and extrathyroidal tumor invasion was identified (P = 0.016); however, the latter factor did not independently predict outcome. There was a trend for suppressive doses of thyroid hormone to improve outcome, particularly with increasing age at diagnosis, but this was not statistically significant. CONCLUSIONS Age is the major determinant of recurrence in pediatric differentiated thyroid carcinoma. The results suggest different tumor biology in young children requiring novel approaches to therapy to decrease recurrence rates.

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

Summary. 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.

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.

Regular exercise improves the well‐being of parents of children with cancer

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.

Rare pattern of relapse to the pancreas and bilateral extraocular muscles in paediatric alveolar rhabdomyosarcoma

Rare pattern of relapse to the pancreas and bilateral extraocular muscles in paediatric alveolar rhabdomyosarcoma Anne L Ryan , Lakshmi Nagarajan, Angela J Alessandri, Nicholas G Gottardo and Rishi S Kotecha Departments of Haematology and Oncology, and Neurology, Princess Margaret Hospital for Children, School of Paediatrics and Child Health, and Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia

Breath-holding spell and macrocytic anaemia in a toddler

A 23-month-old toddler presented with a breath holding episode. She was thriving with normal development and no neurological abnormality. An automated full blood count showed her haemoglobin concentration to be 56 g/l with an MCV of 99 fl [normal range (NR) for age 72–87], an MCH of 33 pg (NR 24–32) and a normal white cell and platelet count. Her serum vitamin B12, red cell folate, thyroid function and liver function tests were normal. She had a markedly raised serum lactate of 4 7 mmol/l without evidence of metabolic acidosis. Further metabolic investigation, which was carried out because of the possibility of a mitochondrial disorder, showed a greatly elevated plasma alanine and plasma proline, at 787 lmol/l (NR 156–547) and 405 lmol/l (NR 59– 369), respectively. Her blood pyruvate was mildly elevated at 0 16 mmol/l (NR < 0 1) whereas her urine metabolic screening was normal. Low faecal pancreatic elastase was suggestive of pancreatic insufficiency. Bone marrow studies showed ring sideroblasts and erythroid cytoplasmic vacuolation (images). Cytogenetic analysis was normal. A diagnosis of Pearson syndrome was confirmed by molecular analysis of bone marrow, which showed a 2-kilobase deletion of mitochondrial DNA. She receives red cell transfusion every 2 months, together with supplements of oral co-enzyme Q10, vitamin C, thiamine and riboflavin. She continues to be well, with normal cardiac function, 9 months after her initial diagnosis. Pearson syndrome is characterized by sideroblastic anaemia with vacuolization of bone marrow precursors and exocrine pancreatic dysfunction. It is caused by sporadic deletions and/or duplications of the mitochondrial DNA, diagnosed by Southern blot analysis of leucocytes, leading to a deficiency in the mitochondrial respiratory chain. Pearson syndrome is often fatal in infancy due to septicaemia, metabolic acidosis or hepatocellular insufficiency.