Dorine Bresters

Azole-Resistant Central Nervous System Aspergillosis

Three patients with central nervous system aspergillosis due to azole-resistant Aspergillus fumigatus (associated with a leucine substitution for histidine at codon 98 [L98H] and a 34-base pair repeat in tandem in the promoter region) are described. The patients were treated with combination therapy or with polyenes, but all patients died. Azole resistance significantly complicates the management of aspergillosis by delaying the initiation of adequate therapy and because effective alternative antifungal drugs are lacking.

High burden of late effects after haematopoietic stem cell transplantation in childhood: a single-centre study

The aim of our study was to assess the cumulative incidence and severity (‘burden’) of late effects in a single-centre cohort of childhood haematopoietic stem cell transplantation (HSCT) survivors, at least 2 years after transplantation. The presence and severity of late effects in each survivor was documented according to the Common Terminology Criteria for Adverse Events (version 3.0). The burden of late effects was graded from mild to disabling/life-threatening. Risk factors for a high burden of late effects were assessed by univariate and multivariate logistic regression analyses. Among 162 survivors of HSCT seen in our late effects outpatient clinic, cumulative incidence of late effects was 93.2% after a median follow-up time of 7.2 years (range 2.0–21.0 years) after HSCT. The burden of late effects was mild, moderate, severe and disabling in 28, 41, 24 and 1% of survivors respectively. Risk factors for a severe or disabling burden of late effects were older age at HSCT (P for trend <0.001) and a conditioning regimen including irradiation OR 2.2, 95% CI 1.1–4.7, P=0.03). In conclusion, a high burden of late effects is found in childhood HSCT survivors after a median follow-up of only 7 years.

The Burden of Cure: Long-term Side Effects Following Hematopoietic Stem Cell Transplantation (HSCT) in Children

Children who survive hematopoietic stem cell transplantation (HSCT) are at risk for an inordinate number of long-term side effects. Late effects can be secondary to the underlying diagnosis for which the transplant is performed, prior treatment of the disease, the transplant preparative regimen, treatment of the complications of transplant, and immunologic interactions between the graft and the host. This article describes the risks and manifestations of the most commonly reported late effects in survivors of pediatric HSCT.

Attitudes of Physicians and Parents Towards Discussing Infertility Risks and Semen Cryopreservation With Male Adolescents Diagnosed With Cancer

In paediatric oncology, the risk of infertility due to treatment constitutes an important problem. For sexually mature male adolescents, sperm cryopreservation is an option, but discussing the topic is complex because of the sensitive nature and the limited time frame. In this article, we determined attitudes and preferred roles of physicians and parents towards discussing sperm banking with male adolescents.

Health‐related quality of life and coping strategies of children after treatment of a malignant bone tumor: A 5‐year follow‐up study

This study was designed to evaluate the development of health‐related quality of life (HRQoL) and coping strategies of children and young adults, who have undergone surgery for a malignant bone tumor in childhood.

Long-term renal function after hemopoietic stem cell transplantation in children

Summary:Glomerular function of all long-term survivors who underwent hemopoietic stem cell transplantation (HSCT) from 1991 to 1998 (study I, n=121) was studied retrospectively. In addition, we prospectively analyzed glomerular and tubular function of all long-term surviving children who received an HSCT between 1998 and 2000 (study II, n=41). We found a lower prevalence of children with chronic renal failure (CRF) post-HSCT in our more recent cohort (study II: 10%) as compared to the older cohort (study I: 24%) 5.0 (0.7 s.d.) and 7.6 (2.4 s.d.) years post-HSCT, respectively. Furthermore, it seems that renal function may stabilize after 1-year post-HSCT. None of the patients required dialysis or antihypertensive medication at long-term follow-up. The sole predictor of CRF in our study was high serum creatinine pre-HSCT (P=0.007), while acute renal failure within 3 months after HSCT (P=0.08) only showed a trend towards predicting CRF. We could not confirm a relation of conditioning with irradiation with CRF post-HSCT, as was shown in several other pediatric and adult studies. Proximal and distal tubular dysfunction only occurred in a minority of long-time survivors of HSCT (3–12 and 9–13%, respectively) and had no clinical consequences.

Using Web-Based and Paper-Based Questionnaires for Collecting Data on Fertility Issues Among Female Childhood Cancer Survivors: Differences in Response Characteristics

Background Web-based questionnaires have become increasingly popular in health research. However, reported response rates vary and response bias may be introduced. Objective The aim of this study was to evaluate whether sending a mixed invitation (paper-based together with Web-based questionnaire) rather than a Web-only invitation (Web-based questionnaire only) results in higher response and participation rates for female childhood cancer survivors filling out a questionnaire on fertility issues. In addition, differences in type of response and characteristics of the responders and nonresponders were investigated. Moreover, factors influencing preferences for either the Web- or paper-based version of the questionnaire were examined. Methods This study is part of a nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female childhood cancer survivors. The Web-based version of the questionnaire was available for participants through the Internet by means of a personalized user name and password. Participants were randomly selected to receive either a mixed invitation (paper-based questionnaire together with log-in details for Web-based questionnaire, n = 137) or a Web-only invitation (log-in details only, n = 140). Furthermore, the latter group could request a paper-based version of the questionnaire by filling out a form. Results Overall response rates were comparable in both randomization groups (83% mixed invitation group vs 89% in Web-only invitation group, P = .20). In addition, participation rates appeared not to differ (66% or 90/137, mixed invitation group vs 59% or 83/140, Web-only invitation group, P =.27). However, in the mixed invitation group, significantly more respondents filled out the paper-based questionnaire compared with the Web-only invitation group (83% or 75/90 and 65% or 54/83, respectively, P = .01). The 44 women who filled out the Web-based version of the questionnaire had a higher educational level than the 129 women who filled out the paper-based version (P = .01). Furthermore, the probability of filling out the Web-based questionnaire appeared to be greater for women who were allocated to the Web-only invitation group (OR = 2.85, 95% CI 1.31 - 6.21), were older (OR = 1.08, 95% CI 1.02 - 1.15), had a higher educational level (OR high vs low = 0.06, 95% CI 0.01 - 0.52), or were students (OR employed vs student = 3.25, 95% CI 1.00 - 10.56). Conclusions Although overall response as well as participation rates to both types of invitations were similar, adding a paper version of a questionnaire to a Web-only invitation resulted in more respondents filling out the paper-based version. In addition, women who were older, had a higher level of education, or were students, were more likely to have filled out the Web-based version of the questionnaire. Given the many advantages of Web-based over paper-based questionnaires, researchers should strongly consider using Web-based questionnaires, although possible response bias when using these types of questionnaires should be taken into account. Trial Registration Nederlands Trial Register NTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922 (Archived by WebCite at http://www.webcitation.org/5zRRdMrDv)

Pulmonary function impairment in children following hematopoietic stem cell transplantation

Deterioration of pulmonary function after hematopoietic stem cell transplantation (SCT) is a well‐known late effect of this treatment, but the course of pulmonary function over time is less clear. The aim of our study was to establish both the prevalence and course of pulmonary function abnormalities in children following SCT.

Parental stress and perceived vulnerability at 5 and 10 years after pediatric SCT

With the aim of assessing parental stress after SCT, 73 parents of children and adolescents who underwent SCT 5 or 10 years ago responded to questionnaires on general distress (General Health Questionnaire (GHQ)), disease-related stress (Pediatric Inventory for Parents-short form (PIP-SF)) and perceptions of child vulnerability (Child Vulnerability Scale (CVS)). General distress scores were comparable with the reference groups, but 40% of the mothers at 5 years after SCT reported increased stress levels as compared with 26% in the community-based reference group. Disease-related stress was comparable with the reference group of parents of children who were just off cancer treatment, 5 years after SCT. At 10 years after SCT, scores were lower than the reference group. Perceived child vulnerability did diminish over time, but remained high in parents of SCT survivors, compared with parents of healthy children: 96% of the parents at 5 years after SCT and 76% of the parents at 10 years after SCT scored above the cutoff point. Perceived vulnerability was found to be a predictor for parental disease-related stress. To conclude, although most parents of SCT survivors are resilient, the majority of parents perceive their child to be much more vulnerable as compared with parents of healthy children. This perception is associated with disease-related stress and may induce overprotective parenting.

A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges

BackgroundAdvances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.MethodsThe study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.DiscussionThe DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatric cancer patients as well as long-term survivors of childhood cancer. Other investigators planning to conduct large cohort studies on late effects may encounter similar challenges as those encountered during this study. The solutions to these challenges described in this paper may be useful to these investigators.Trial registrationNTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922