Johannes Rischewski

Splenectomy in children with idiopathic thrombocytopenic purpura : A prospective study of 134 children from the Intercontinental Childhood ITP Study Group

Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited.

Newly diagnosed immune thrombocytopenia in children and adults: A comparative prospective observational registry of the intercontinental cooperative immune thrombocytopenia study group

Background Primary immune thrombocytopenia is a bleeding diathesis with an unknown etiology in predisposed individuals with immune disturbances. Although it is claimed that children and adults differ in clinical and laboratory aspects, few data exist to corroborate this observation. Our objective was to assess comparative data from children and adults with newly diagnosed immune thrombocytopenia. Design and Methods Clinical and laboratory data of 1,784 children and 340 adults were extracted from the Pediatric and Adult Registry on Chronic Immune Thrombocytopenia. The registry represents a prospective cohort of children and adults with newly diagnosed immune thrombocytopenia. Participating investigators registered their patients immediately after the diagnosis using a web based data transfer. Children aged under 16 years were compared with adults aged 16 years and over with descriptive statistical analyses. Results The presenting mean platelet count of children and adults was 18.1 and 25.4×109/L. Signs of bleeding were reported in 24% of children and in 23% of adults, and intracranial hemorrhage in 10 of 1,784 children and in 6 of 340 adults. Co-morbidity was observed in 3.9% of children and in 30% of adults. Bone marrow aspiration and laboratory tests (antinuclear antibodies, human immunodeficiency and hepatitis C virus) were performed more frequently in adults. Children and adults were followed with a ‘watch and wait’ strategy in 20% and in 29%, respectively. Immunoglobulins were used more frequently in children and corticosteroids in adults. Conclusions Comparative data of children and adults with newly diagnosed immune thrombocytopenia revealed similarities in presenting platelet counts and in bleeding, whereas differences occurred in co-morbidity, diagnostic procedures and therapy.

Background Ionizing Radiation and the Risk of Childhood Cancer: A Census-Based Nationwide Cohort Study

Background Exposure to medium or high doses of ionizing radiation is a known risk factor for cancer in children. The extent to which low-dose radiation from natural sources contributes to the risk of childhood cancer remains unclear. Objectives In a nationwide census-based cohort study, we investigated whether the incidence of childhood cancer was associated with background radiation from terrestrial gamma and cosmic rays. Methods Children < 16 years of age in the Swiss National Censuses in 1990 and 2000 were included. The follow-up period lasted until 2008, and incident cancer cases were identified from the Swiss Childhood Cancer Registry. A radiation model was used to predict dose rates from terrestrial and cosmic radiation at locations of residence. Cox regression models were used to assess associations between cancer risk and dose rates and cumulative dose since birth. Results Among 2,093,660 children included at census, 1,782 incident cases of cancer were identified including 530 with leukemia, 328 with lymphoma, and 423 with a tumor of the central nervous system (CNS). Hazard ratios for each millisievert increase in cumulative dose of external radiation were 1.03 (95% CI: 1.01, 1.05) for any cancer, 1.04 (95% CI: 1.00, 1.08) for leukemia, 1.01 (95% CI: 0.96, 1.05) for lymphoma, and 1.04 (95% CI: 1.00, 1.08) for CNS tumors. Adjustment for a range of potential confounders had little effect on the results. Conclusions Our study suggests that background radiation may contribute to the risk of cancer in children, including leukemia and CNS tumors. Citation Spycher BD, Lupatsch JE, Zwahlen M, Röösli M, Niggli F, Grotzer MA, Rischewski J, Egger M, Kuehni CE, for the Swiss Pediatric Oncology Group and the Swiss National Cohort. 2015. Background ionizing radiation and the risk of childhood cancer: a census-based nationwide cohort study. Environ Health Perspect 123:622–628; http://dx.doi.org/10.1289/ehp.1408548

Adolescent survivors of childhood cancer: are they vulnerable for psychological distress?†

We aimed to (i) evaluate psychological distress in adolescent survivors of childhood cancer and compare them to siblings and a norm population; (ii) compare the severity of distress of distressed survivors and siblings with that of psychotherapy patients; and (iii) determine risk factors for psychological distress in survivors.

Idiopathic thrombocytopenic purpura (ITP): is there a genetic predisposition?

Idiopathic thrombocytopenic purpura (ITP) is a diagnosis of exclusion. It is unknown, whether familial ITP exists. Familial cases would make a genetic susceptibility for ITP possible. Data of the Pediatric and Adult Registry on Chronic ITP (PARC‐ITP) were reviewed and subsequently ITP patients from Basel investigated for cases with a positive family history. In 10 of 445 pediatric patients and in 2 of 21 patients from Basel the family history was positive. A surprisingly high number of ITP patients with a positive family history were identified, indicating the likely existence of a genetic susceptibility for ITP. Pediatr Blood Cancer 2006;47:678–680.

Molecular analysis in glycogen storage disease 1 non-A: DHPLC detection of the highly prevalent exon 8 mutations of the G6PT1 gene in German patients.

We investigated the molecular basis of glycogen storage disease type 1 non‐A (GSD�1 non‐A) in 21�patients. In addition to 8 novel mutations within the G6PT1 gene (c.250T>A, c.580G>A, c.627C>T, c.653‐4delAG, c.844C>A, c.1071A>C, c.1268G>A, c.1348G>A), we found a remarkably high prevalence of exon 8 mutations in German patients. The c.1211‐2delCT mutation and the c.1184G>T mutation accounted for 32% and 29% of mutant chromosomes, respectively, supporting the hypothesis of a Middle European origin of these two mutations. Together with less common mutations, 79% of German GSD�1 non‐A patients were either homozygous or heterozygous for an exon 8 mutation. In addition to direct sequencing, these exon�8 mutations could be detected by mutation‐specific methods such as the detection of heteroduplex formation on polyacrylamide gel electrophoresis or by the amplification of DNA segments by allele‐specific oligonucleotides. Furthermore, the use of denaturating high performance liquid chromatography (DHPLC) allowed a 100% detection and discrimination of all exon 8 mutations. In conclusion from these results, we recommend the use of either conventional or DHPLC screening as the initial non‐invasive and efficient diagnostic procedure in patients with GSD�1 non‐A from populations with a similar distribution of mutations. Hum Mutat 16:177, 2000.

Physical and not mental health is impaired in very long-term survivors after HSCT compared with their respective donors: a paired analysis

To the editor: Bhatia and colleagues[1][1] recently published a comprehensive analysis on late mortality after allogeneic hematopoietic stem cell transplantation (HSCT), providing interesting data about the functional status of 547 recipients and 319 siblings. At the time of this Collaborative Bone

Tumor incidence in related hematopoietic stem cell donors

Late malignancies have been discussed as a potential risk for growth factor mobilized donors of hematopoietic stem cells. Little is known about the incidence and potential risk factors. This single center retrospective cohort study evaluated all HLA-identical sibling pairs with hematopoietic stem cell transplantation (HSCT) for a hematological malignancy, treated from 1974 to 2001 at the University Hospital of Basel. Three hundred eighteen pairs were identified, 291 donors (92%) could be contacted. Median observation time was 13.8 years (range 5–32 years). Sixteen (5%) donors had developed a total of 18 tumors, 17 recipients a secondary tumor. According to the age- and sex-adapted cancer incidence, 3.3 tumors in male and 6.8 in female donors were expected, 3 (relative risk (RR): 0.91, 95% confidence interval: 0.19–2.66) and 4 (RR: 0.58, 95% confidence interval: 0.16–1.48), respectively, were found in donors between 0 and 49 years. Between 50 and 69 years, 4.5 tumors in males and 4.8 in females were expected, 5 (RR: 1.11, 95% confidence interval: 0.36–2.59) and 6 (RR: 1.23, 95% confidence interval: 0.45–2.67), respectively, were observed. Tumors do occur in donors of hematopoietic stem cells at least at the rate as expected in a normal population; whether incidence exceeds expected rates needs to be determined in larger international cohorts.

Better to know than to imagine: Including children in their health care

ABSTRACT Background: This article describes the overall attitudes of children, their parents, and attending physicians toward including or excluding pediatric patients in medical communication and health care decision-making processes. Methods: Fifty-two interviews were carried out with pediatric patients (n = 17), their parents (n = 19), and attending oncologists (n = 16) in eight Swiss pediatric oncology centers. The interviews were analyzed using thematic coding. Results: Parenting styles, the childs personality, and maturity are factors that have a great impact upon the inclusion of children in their health care processes. Children reported the desire to be heard and involved, but they did not want to dominate the decision-making process. Ensuring trust in the parent–child and physician–patient relationships and respecting the child as the affected person were important values determining childrens involvement. These two considerations were closely connected with the concern that fantasies are often worse than reality. Seeking childrens compliance with treatment was a practical but critical reason for informing them about their health care. The urge to protect them from upsetting news sometimes resulted in their (partial) exclusion. Conclusions: The ethical imperative for inclusion of children in their health care choices was not so much determined by the right for self-determination, but by the need to include them. If children are excluded, they imagine things, become more isolated, and are left alone with their fears. Nevertheless, the urge to protect children is innate, as adults often underestimate childrens coping capacities.

Employment Situation of Parents of Long-Term Childhood Cancer Survivors

Background Taking care of children diagnosed with cancer affects parents’ professional life. The impact in the long-term however, is not clear. We aimed to compare the employment situation of parents of long-term childhood cancer survivors with control parents of the general population, and to identify clinical and socio-demographic factors associated with parental employment. Methods As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of survivors aged 5–15 years, who survived ≥5 years after diagnosis. Information on control parents of the general population came from the Swiss Health Survey (restricted to men and women with ≥1 child aged 5–15 years). Employment was categorized as not employed, part-time, and full-time employed. We used generalized ordered logistic regression to determine associations with clinical and socio-demographic factors. Clinical data was available from the Swiss Childhood Cancer Registry. Results We included 394 parent-couples of survivors and 3’341 control parents (1’731 mothers; 1’610 fathers). Mothers of survivors were more often not employed (29% versus 22%; ptrend = 0.007). However, no differences between mothers were found in multivariable analysis. Fathers of survivors were more often employed full-time (93% versus 87%; ptrend = 0.002), which remained significant in multivariable analysis. Among parents of survivors, mothers with tertiary education (OR = 2.40, CI:1.14–5.07) were more likely to be employed. Having a migration background (OR = 3.63, CI: 1.71–7.71) increased the likelihood of being full-time employed in mothers of survivors. Less likely to be employed were mothers of survivors diagnosed with lymphoma (OR = 0.31, CI:0.13–0.73) and >2 children (OR = 0.48, CI:0.30–0.75); and fathers of survivors who had had a relapse (OR = 0.13, CI:0.04–0.36). Conclusion Employment situation of parents of long-term survivors reflected the more traditional parenting roles. Specific support for parents with low education, additional children, and whose child had a more severe cancer disease could improve their long-term employment situation.