John A. Heath

CHILDHOOD CANCER: Its Impact and Financial Costs for Australian Families

This study evaluated the impact and financial costs of childhood cancer for Australian families by means of a nonrandomized retrospective cross-sectional survey at the oncology department of a large metropolitan pediatric hospital. The Family Impact Scale (a standardized questionnaire) and the self-reported economic burden (a questionnaire on expenses and lifestyle changes) were utilized. Results of the family impact score were compared to a previously published cohort of children with insulin-dependent diabetes mellitus. The participants were 56 parents of children newly diagnosed with cancer in the year 2002. In addition to the expected high social and emotional impacts, the majority of families reported suffering from great or moderate economic hardship. Factors predictive for families at risk included single parenthood, lower household income, and greater distance from the hospital. The results show that the distribution of resources is not equitable and is currently failing to negate significant financial stresses for many Australian families.

Unmeasured Costs of a Child's Death: Perceived Financial Burden, Work Disruptions, and Economic Coping Strategies Used by American and Australian Families Who Lost Children to Cancer

PURPOSE Financial concerns represent a major stressor for families of children with cancer but remain poorly understood among those with terminally ill children. We describe the financial hardship, work disruptions, income loss, and coping strategies of families who lost children to cancer. METHODS Retrospective cross-sectional survey of 141 American and 89 Australian bereaved parents whose children died between 1990 and 1999 and 1996 to 2004, respectively, at three tertiary-care pediatric hospitals (two American, one Australian). Response rate: 63%. RESULTS Thirty-four (24%) of 141 families from US centers and 34 (39%) of 88 families from the Australian center reported a great deal of financial hardship resulting from their childrens illness. Work disruptions were substantial (84% in the United States, 88% in Australia). Australian families were more likely to report quitting a job (49% in Australia v 35% in the United States; P = .037). Sixty percent of families lost more than 10% of their annual income as a result of work disruptions. Australians were more likely to lose more than 40% of their income (34% in Australia v 19% in the United States; P = .035). Poor families experienced the greatest income loss. After accounting for income loss, 16% of American and 22% of Australian families dropped below the poverty line. Financial hardship was associated with poverty and income loss in all centers. Fundraising was the most common financial coping strategy (52% in the United States v 33% in Australia), followed by reduced spending. CONCLUSION In these US and Australian centers, significant household-level financial effects of a childs death as a result of cancer were observed, especially for poor families. Interventions aimed at reducing the effects of income loss may ease financial distress.

Temozolomide in pediatric low‐grade glioma

We describe a retrospective series of children with low‐grade glioma who received temozolomide.

Human Granulocyte Colony-Stimulating Factor in Children With High-Risk Acute Lymphoblastic Leukemia: A Children’s Cancer Group Study

PURPOSE To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on hematopoietic toxicities, supportive care requirements, time to complete intensive therapy, and event-free survival (EFS) and overall survival (OS) in children with high-risk acute lymphoblastic leukemia (HR-ALL). PATIENTS AND METHODS A total of 287 children with HR-ALL were randomly assigned to intensive chemotherapy regimens (New York I [NY I] or NY II) as part of the Childrens Cancer Group (CCG)-1901 protocol. The induction phases consisted of five drugs (vincristine, prednisone, l-asparaginase, daunorubicin, and cyclophosphamide). Initial consolidation comprised six-agent chemotherapy combined with 18 Gy of total-brain irradiation. Patients were randomly assigned to receive G-CSF (5 microg/kg/day) during either induction or initial consolidation. A crossover study analysis was done on the 259 patients who completed both phases of therapy. RESULTS The mean time to neutrophil recovery (>/= 0.5 x 109/L) was reduced with G-CSF (16.7 v 19.1 days, P =.0003); however, patients who received G-CSF did not have significantly reduced episodes of febrile neutropenia (149 v 164, P =.41), positive blood cultures (57 v 61, P =.66), or serious infections (75 v 79, P =.62). Hospitalization (14.0 v 13.9 days, P =.87) and induction therapy completion times (NY I, 30.3 v 31.3 days, P =.11; NY II, 33.4 v 32.3 days, P =.40) were not significantly altered. There were no differences in 6-year EFS (P =.24) or OS (P =.54) between patients receiving or not receiving G-CSF on CCG-1901, NY I and NY II. CONCLUSION Children with high-risk ALL do not appear to benefit from prophylactic G-CSF.

Estrogen as treatment of hemorrhagic cystitis in children and adolescents undergoing bone marrow transplantation.

Hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) can cause significant morbidity and mortality. Previous reports have suggested a role for estrogen in the control of HC in adult patients. Here, we describe the clinical courses of 10 children and adolescents treated with estrogen for HC following HSCT. Eight patients (80%) experienced a significant improvement in their hematuria following the commencement of therapy, with six (60%) undergoing resolution of macroscopic hematuria, without any recurrences. The treatment was well tolerated by the majority of patients, with only one patient needing to interrupt treatment (hepatotoxicity). We conclude that estrogen is well tolerated and often effective, and should be considered as an adjunctive treatment option in children and adolescents with HC following HSCT.

Parental alcohol consumption and risk of childhood acute lymphoblastic leukemia and brain tumors

PurposeChildhood acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and brain tumors (CBTs) are the leading cause of cancer death in children. In our Australian case–control studies of these cancers, we investigated whether parental alcohol consumption before or during pregnancy was associated with risk.MethodsCases were identified through the ten Australian pediatric oncology centers, and controls were recruited through national random-digit dialling. Detailed information on alcohol consumption, including beverage type, amount, and timing, was collected from 690 case families (388 ALL and 302 CBT) and 1,396 control families. Data were analyzed using unconditional logistic regression.ResultsWe found no evidence that maternal alcohol use before or during pregnancy was associated with an increased risk of either cancer; rather, there was evidence of inverse associations, particularly with wine. For both cancers, we observed U-shaped associations with paternal alcohol consumption in the year before the pregnancy, possibly driven by reduced risk at moderate levels of beer and wine intake and increased risk associated with high levels of beer intake. Moderate intake of spirits by fathers was associated with an increased risk of CBT but not ALL. These findings would be strengthened by corroboration in other studies. While the inverse associations with wine may be interesting mechanistically, the public health message remains that maternal alcohol use during pregnancy causes serious disorders in the offspring and should be avoided.ConclusionsOur findings suggest that men, as well as women, should limit their alcohol intake when planning a pregnancy.

Survivors of childhood cancer: An Australian audit of vaccination status after treatment

Survivors of childhood and adolescent cancer are at risk of vaccine preventable diseases and are recommended to receive booster vaccinations post‐chemotherapy. The aim of this study was to describe the compliance of post‐chemotherapy revaccination of childhood cancer survivors relative to current Australian guidelines.

TP53, BRCA1, and BRCA2 Tumor Suppressor Genes Are Not Commonly Mutated in Survivors of Hodgkin’s Disease With Second Primary Neoplasms

PURPOSE Despite recognition that second malignant neoplasms (SMNs) contribute significantly to mortality after the successful treatment of Hodgkins disease (HD), little is known about the molecular events leading to secondary tumors. Factors contributing to second cancer risk include the carcinogenic effects of ionizing radiation and chemotherapy, in combination with possible host susceptibility. To clarify whether host genetic factors contribute to secondary tumorigenesis, we performed mutational analyses of the TP53, BRCA1, and BRCA2 tumor suppressor genes in a cohort of 44 HD patients developing one or more SMN. PATIENTS AND METHODS Family cancer histories and constitutional DNA samples were obtained from 44 HD patients with SMNs identified. Using DNA-based sequencing, we evaluated the TP53 gene in all 44 patients. Nineteen female patients developing one or more secondary breast cancer were also analyzed for mutations in the BRCA1 and BRCA2 breast cancer-susceptibility genes. RESULTS Nineteen patients (43%) had more than one SMN, and 12 patients (27%) had a positive family history of cancer. One of 44 patients tested for TP53 harbored a novel homozygous germline abnormality. One of 19 patients tested for BRCA2 carried a previously described heterozygous inactivating mutation. We identified no germline BRCA1 mutations. CONCLUSION Despite features suggestive of genetic predisposition, the TP53, BRCA1, and BRCA2 genes were not frequently mutated in this cohort of HD patients developing SMNs. Larger studies of these genes or investigations of other genes involved in cellular DNA damage response pathways may identify host genetic factors that contribute to secondary tumorigenesis.

Pythium insidiosum Pleuropericarditis Complicating Pneumonia in a Child with Leukemia

We describe a 12-year-old boy with acute myeloid leukemia who developed pleuropericarditis while he was neutropenic and was receiving intravenously administered antibiotic and antifungal therapy for pneumonia. A KOH preparation of the purulent material from an extensive diagnostic and therapeutic pleuropericardial drainage procedure revealed multiple irregularly septate hyphae, and cultures yielded the organism Pythium insidiosum. After completing a 12-month course of intravenously administered liposomal amphotericin B (AmBisome; Fujisawa Healthcare) and itraconazole, the patient remained alive, in clinical remission, and symptom free.

Physical activity in survivors of childhood acute lymphoblastic leukaemia

Aim:  To objectively measure levels of physical activity in children, following treatment for acute lymphoblastic leukaemia (ALL).