Gertjan J L Kaspers

VU University Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (320)1694.68 Total impact

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    ABSTRACT: Children with and after cancer are found to have a decreased physical fitness, frequently resulting in decreased physical functioning. The gold standard test for assessing aerobic fitness, a component of physical fitness, is the respiratory gas analyses--based cardiopulmonary exercise test (CPET). However, equipment for gas analysis is often unavailable in local physical therapy centres and non--university hospitals. The Steep Ramp Test (SRT), is a cycle ergometer test with a fast increase in workload, a short duration, and does not require respiratory gas analysis equipment. The aim of this study was to compare the results of the CPET and the SRT, in children with cancer, and to assess whether the SRT can be used for aerobic fitness assessment in clinical practice in this population. This study is a cross--sectional assessment using baseline data of a randomized controlled trial. The study was performed in a hospital setting. Sixty--one children (mean age 12.9 years; 33 boys) with cancer were included in the analysis; 16 children were on non--intensive chemotherapy treatment, 45 were in the first year thereafter. Participants performed both the SRT and the CPET on a cycle ergometer with respiratory gas analysis. Data of the two tests were compared and regression analyses were performed. CPET test results revealed a higher impact on the cardiovascular system, as shown by higher peak ventilation (47.8 versus 52.0 Litres per min) and peak heart rates (173 versus 191 beats per min), compared to the SRT. In addition, the test time was significantly longer (90 s versus 390 s). Yet, the primary outcome of the SRT (peak work rate) was able to reliably estimate the peak oxygen uptake of the CPET. The peak oxygen uptake was comparable between the SRT and the CPET, although the peak work rate was significantly higher during the SRT. This study showed that the SRT is a valid instrument to assess aerobic fitness in children with cancer. The SRT is less time consuming and can be performed without gas analysis in a non--clinical setting, making it less demanding for children.
    European journal of physical and rehabilitation medicine. 11/2014;
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    ABSTRACT: Background: According to the results of the international study Relapsed AML 2001/01 response was better after re-induction with L-DNR/FLAG (liposomal daunorubicin, fludarabine, cytarabine, G-CSF) compared to FLAG only but survival rate was not improved. However, the findings might be group-specific. Method: Patient characteristics, actual therapy given and long-term course of the disease in 155 pediatric patients (including non-randomized) with first relapse and 10 primary nonresponders treated in Germany were analyzed. Results: Overall 4-year survival rates after relapse were similar in the 2 treatment groups L-DNR/FLAG and FLAG (0.43±0.05 vs. 0.47±0.06, p(log-rank)=0.47). The rate of randomization was low (65%) and 5% of the 101 randomized patients changed the treatment arm. Therefore, induction was based in 40% patients on an individual decision with preference for L-DNR/FLAG. There were less patients with favorable cytogenetics and morphology in the L-DNR/FLAG-group (p<0.04). Response to the first re-induction course at day 28 tended to be more unfavorable with FLAG only. In this patient group protocol intensifications were more frequent as compared to the L-DNR/FLAG-group (p=0.07), and late CR could be achieved after intensification in 9/18 poor responding patients. Conclusion: The initial selection bias of relapse patients with unfavorable risk factors to the disadvantage of the L-DNR/FLAG-group and the more drug- and time-intensive treatment after 1(st) re-induction given in the FLAG-group may have nullified the initial beneficial effect of L-DNR containing re-induction therapy and led to similar and relatively favorable survival rates in both treatment groups in Germany. © Georg Thieme Verlag KG Stuttgart · New York.
    Klinische Padiatrie. 11/2014; 226(6/07):323-331.
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    ABSTRACT: Our study explores socioeconomic, treatment-related, and psychological experiences of parents during cancer treatment of their children at an academic hospital in Kenya.
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 10/2014;
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    ABSTRACT: Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients.
    Journal of neuroscience methods. 09/2014;
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    ABSTRACT: Adrenocortical carcinoma (ACC) is rare in both adult and pediatric populations. Literature suggests significant differences between children and adults in presentation, histological properties and outcome. The aim of this first nationwide study on pediatric ACC was to describe the incidence, presentation, pathological characteristics, treatment and survival in The Netherlands. All ACC patients aged <20 years at diagnosis and registered in the population-based Netherlands Cancer Registry between 1993 and 2010 were included. Clinical data were extracted from medical records. Archival histological slides were collected via the Dutch Pathology Registry (PALGA). We compared our findings to all clinical studies on pediatric ACC that were found on PubMed. Based on the results, 12 patients were identified: 8 females and 4 males. The median age was 4.1 years (range 1.1-18.6). The population-based age-standardized incidence rate for patients <20 years was 0.18 per million person-years. Autonomous hormonal secretion was present in 10 patients. Seven patients were aged ≤4 years at diagnosis, 5 presented with localized disease and 2 with locally advanced disease. Five patients were aged ≥5 years, 3 presented with distant metastases and 1 with locally advanced disease. For all patients, histological examination displayed malignant characteristics. All patients aged ≤4 years at diagnosis survived; the median follow-up was 97 months (57-179 months). All patients aged ≥5 years died; the median survival was 6 months (0-38 months). Pediatric ACC is extremely rare in the Western world. The clinical outcome was remarkably better in patients aged ≤4 years. This is in accordance with less advanced stage of disease at presentation, yet contrasts with the presence of adverse histological characteristics. Clinical management in advanced disease is adapted from adult practice in the absence of evidence regarding pediatric ACC.
    Oncology reports. 09/2014;
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    ABSTRACT: Background Wilms tumour postoperative chemotherapy is ideally stratified according to the pathologist's assessment of tumour stage and risk classification (tumour type). In sub-Saharan Africa results are often not available in time to influence therapy and in Malawi surgical staging has been used to stratify postoperative chemotherapy. Here we compare the results from surgical and both local pathology and central pathology review.ProcedureChildren diagnosed with a Wilms tumour in Blantyre, Malawi between 2007 and 2011 were included if they had a nephrectomy and the pathology slides were available. All tumour specimens were assessed in three different ways: the local surgeon documented the surgical stage of the tumour, and the risk classification and pathology stage were assessed both by the local pathologist and by a SIOP central review pathologist in Europe.ResultsFifty patients had complete data available and were included in the analyses. Tumour risk classification differed between the local and central pathology review in only two patients (4%). Using central pathology review as the gold standard 60% of patients received the correct postoperative chemotherapy treatment based on surgical staging and 84% based on the local pathology stage and risk classification.Conclusion Local pathology capacity building is needed to enable timely assessment and reporting. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 09/2014; · 2.35 Impact Factor
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    ABSTRACT: Improvement in survival of pediatric acute lymphoblastic leukemia (ALL) has increased the attention to quality of life (QoL) . QoL is impaired during maintenance treatment, but little is known about QoL during induction therapy. Identification of patients with poor QoL during induction will provide opportunities for early interventions, and may subsequently improve future QoL. This national multi-center study aimed to assess QoL and its determinants during ALL induction treatment.
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 07/2014;
  • Pediatric hematology and oncology. 07/2014;
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    ABSTRACT: Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n = 198) of relapsed non-French-American-British M3, non-Down syndrome AML patients that received similar relapse treatment. We correlated molecular aberrations with clinical and biological factors and studied their prognostic relevance. Hotspot mutations in the analysed genes were detected in 92 out of 198 patients (46·5%). In 72 of these 92 patients (78%), molecular aberrations were mutually exclusive for the currently analysed genes. FLT3-internal tandem repeat (ITD) (18% of total group) mutations were most frequent, followed by NRAS (10·2%), KRAS (8%), WT1 (8%), KIT (8%), NPM1 (5%) and FLT3-tyrosine kinase domain (3%) mutations. Presence of a WT1 aberration was an independent risk factor for second relapse (Hazard Ratio [HR] = 2·74, P = 0·013). In patients who achieved second complete remission (70·2%), WT1 and FLT3-ITD aberrations were independent risk factors for poor overall survival (HR = 2·32, P = 0·038 and HR = 1·89, P = 0·045 respectively). These data show that molecular aberrations at first relapse are of prognostic relevance and potentially useful for risk group stratification of paediatric relapsed AML and for identification of patients eligible for personalized treatment.
    British Journal of Haematology 06/2014; · 4.94 Impact Factor
  • Acta Neuropathologica 06/2014; · 9.73 Impact Factor
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    ABSTRACT: Although diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis of all pediatric brain tumors, studies on prognostic factors in DIPG are sparse. To control for confounding variables in DIPG studies, which generally include relatively small patient numbers, a survival prediction tool is needed.
    Neuro-Oncology 06/2014; · 6.18 Impact Factor
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    ABSTRACT: Background: Chemotherapy and radiotherapy for childhood cancer can result in a decreased reproductive function. It is therefore important that paediatric oncologists discuss the possible impact of treatment on female fertility and available fertility preservation options with their patients. However, it is unknown what Dutch paediatric oncologists know about of the effect of cancer treatment on female fertility, whether or not they address this issue in clinical practice, what their attitudes are towards addressing fertility after cancer treatment and fertility preservation options, and to what extent they require additional information resources. Methods: In this nationwide quantitative cross-sectional study a survey was sent to all registered paediatric oncologists in the Netherlands (n=64). Results: Thirty-seven paediatric oncologists participated (participation rate 58%). Fertility issues were discussed with patients and÷or parents by 97%. Of the paediatric oncologists, 54-76% were aware of possibilities for fertility preservation; however only.
    The Netherlands Journal of Medicine 06/2014; 72(5):264-70. · 2.38 Impact Factor
  • Gertjan Kaspers
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    ABSTRACT: The prognosis of paediatric acute myeloid leukaemia (AML) has improved significantly over the recent decades, but still about one-third of patients relapse. These patients have a relatively poor prognosis, with a probability of long-term survival from relapse of about 35%. This can only be achieved with very intensive chemotherapy and, usually, allogeneic stem cell transplantation, leading to very significant toxicity and even treatment-related mortality. Major improvements in the treatment of paediatric relapsed AML thus are required still, and several possibilities are discussed. In case of a suspected relapse, a comprehensive diagnostic work-up has to be undertaken, because significant changes in the biological features of the AML cells may have occurred between initial diagnosis and relapse. This review discusses many practical issues that one encounters in the treatment of children with relapsed AML. It will also be of interest for those involved in translational research in AML.
    British Journal of Haematology 05/2014; · 4.94 Impact Factor
  • Haematologica 05/2014; · 5.94 Impact Factor
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    ABSTRACT: Background The principal reason for childhood cancer treatment failure in low-income countries is treatment abandonment, the most severe form of nonadherence. Two often neglected factors that may contribute to treatment abandonment are as follows: (a) lack of information and guidance by doctors, along with the negative beliefs of family and friends advising parents, which contributes to misconceptions regarding cancer and its treatment, and (b) a widespread policy in public hospitals by which children are retained after doctor's discharge until medical bills are settled.Objective This study explored parents' experiences with hospital retention policies in a Kenyan academic hospital and the impact of attitudes of family and friends on parents' decisions about continuing cancer treatment for their child.Methods Home visits were conducted to interview parents of childhood cancer patients who had been diagnosed between 2007 and 2009 and who had abandoned cancer treatment.ResultsRetrospective chart review revealed 98 children diagnosed between 2007 and 2009 whose parents had made the decisions to abandon treatment. During 2011–2012, 53 families (54%) could be reached, and 46 (87%) of these agreed to be interviewed. Parents reported the attitudes of community members (grandparents, relatives, friends, villagers, and church members); 61% believed that the child had been bewitched by some individual, and 74% advised parents to seek alternative treatment or advised them to stop medical treatment (54%). Parents also reported that they were influenced by discussions with other parents who had a child being treated, including that their child's life was in God's hands (87%), the trauma to the child and family of forced hospital stays (84%), the importance of completing treatment (81%), the financial burden of treatment (77%), and the incurability of cancer (74%). These discussions influenced their perceptions of cancer treatment and its usefulness (65%). Thirty-six families (78%) had no health insurance, and 19 of these parents (53%) could not pay their medical bills and were not allowed to take their child home when treatment ended. Parents reported feelings of desperation (95%), powerlessness (95%), and sadness (84%) and that their child has been imprisoned (80%), during the period of retention. The majority of parents (87%) felt that hospital retention of children must cease.Conclusions The attitudes and beliefs of parents of children with cancer are impacted by those close to them and their community and may influence their perceptions of cancer treatment and decisions to stop treatment. Hospital retention policies are highly distressing for parents and may contribute to both treatment delays and treatment abandonment. These factors jeopardize treatment outcomes for young patients and require attention and modification. Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 05/2014; · 3.51 Impact Factor
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    ABSTRACT: Background: Efficacy of childhood cancer treatment in low-income countries may be impacted by parents' and health-care providers' perspectives on chemotherapy-related side-effects. This study explores prevalence and severity of side-effects in childhood cancer, and compares health beliefs about side-effects between parents and health-care providers, and between nurses and doctors in Indonesia. Materials and Methods: Semi-structured questionnaires were filled in by 40 parents and 207 health-care providers in an academic hospital. Results: Parents exporessed a desire to receive more information about side-effects (98%) and worried about this aspect of treatment (90%), although side-effects were less severe than expected (66%). The most frequent was behavior alteration (98%) and the most severe was hair loss. Only 26% of parents consulted doctors about side-effects. More parents, compared to health-care providers, believed that medicines work better when side-effects are more severe (p<0.001), and accepted severe side-effects (p=0.021). More health-care providers, compared to parents, believed that chemotherapy can be stopped or the dosage altered when there are side-effects (p=0.011). More nurses, compared to doctors, stated that side-effects were unbearable (p=0.004) and made them doubt efficacy of treatment (p<0.001). Conclusions: Behavior alteration is the most frequent and hair loss the most severe side-effect. Apparent discrepancies in health beliefs about side-effects exist between parents and health-care providers. A sustainable parental education program about side-effects is recommended. Health-care providers need to update and improve their knowledge and communication skills in order to give appropriate information. Suchmeasures may improve outcome of childhood cancer treatment in low-income countries, where adherence to therapy is a major issue.
    Asian Pacific journal of cancer prevention: APJCP 04/2014; 15(8):3593-9. · 1.50 Impact Factor
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    ABSTRACT: Diffuse intrinsic pontine glioma (DIPG), with a median survival of only 9 months, is the leading cause of pediatric brain cancer mortality. Dearth of tumor tissue for research has limited progress in this disease until recently. New experimental models for DIPG research are now emerging. To develop preclinical models of DIPG, two different methods were adopted: cells obtained at autopsy (1) were directly xenografted orthotopically into the pons of immunodeficient mice without an intervening cell culture step or (2) were first cultured in vitro and, upon successful expansion, injected in vivo. Both strategies resulted in pontine tumors histopathologically similar to the original human DIPG tumors. However, following the direct transplantation method all tumors proved to be composed of murine and not of human cells. This is in contrast to the indirect method that included initial in vitro culture and resulted in xenografts comprising human cells. Of note, direct injection of cells obtained postmortem from the pons and frontal lobe of human brains not affected by cancer did not give rise to neoplasms. The murine pontine tumors exhibited an immunophenotype similar to human DIPG, but were also positive for microglia/macrophage markers, such as CD45, CD68 and CD11b. Serial orthotopic injection of these murine cells results in lethal tumors in recipient mice. Direct injection of human DIPG cells in vivo can give rise to malignant murine tumors. This represents an important caveat for xenotransplantation models of DIPG. In contrast, an initial in vitro culture step can allow establishment of human orthotopic xenografts. The mechanism underlying this phenomenon observed with direct xenotransplantation remains an open question.
    Acta Neuropathologica 04/2014; · 9.73 Impact Factor
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    ABSTRACT: Salinosporamide A (NPI-0052, marizomib) is a naturally-occurring proteasome inhibitor derived from the marine actinobacterium Salinispora tropica and represents a promising clinical agent in the treatment of hematologic malignancies. Recently, these actinobacteria were shown to harbor self-resistance properties to salinosporamide A by expressing redundant catalytically-active mutants of the 20S proteasome β-subunit, reminiscent of PSMB5 mutations identified in cancer cells with acquired resistance to the founding proteasome inhibitor, bortezomib. Here, we assessed the growth inhibitory potential of salinosporamide A in human acute lymphocytic leukemia CCRF-CEM cells, and its 10-fold (CEM/BTZ7), and 123-fold (CEM/BTZ200) bortezomib-resistant sublines harboring PSMB5 mutations. Parental cells displayed sensitivity to salinosporamide A (IC50= 5.1 nM), whereas their bortezomib-resistant sublines were 9- and 17-fold cross-resistant to salinosporamide A, respectively. Notably, combination experiments of salinosporamide A and bortezomib showed synergistic activity in CEM/BTZ200 cells. CEM cells gradually exposed to 20 nM salinosporamide A (CEM/S20) displayed stable 5-fold acquired resistance to salinosporamide A and were 3-fold cross-resistant to bortezomib. Consistent with the acquisition of a PSMB5 point mutation (Met45Val) in CEM/S20 cells, salinosporamide A displayed a markedly impaired capacity to inhibit β5-associated catalytic activity. Lastly, compared to parental CEM cells, CEM/S20 cells exhibited up to 2.5-fold upregulation of constitutive proteasome subunits, while retaining unaltered immunoproteasome subunit expression. In conclusion, salinosporamide A displayed potent antileukemic activity against bortezomib-resistant leukemia cells. β-subunit point mutations as a common feature of acquired resistance to salinosporamide A and bortezomib in hematologic cells and Salinispora tropica suggest an evolutionarily conserved mechanism of resistance to proteasome inhibitors.
    Molecular pharmacology 04/2014; · 4.53 Impact Factor
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    ABSTRACT: Pediatric acute lymphoblastic leukemia (ALL) is treated with combination chemotherapy including mercaptopurine (6MP) as an important component. Upon its uptake, 6MP undergoes a complex metabolism involving many enzymes and active products. The prognostic value of all the factors engaged in this pathway still remains unclear. This study attempted to determine which components of 6MP metabolism in leukemic blasts and red blood cells are important for 6MP's sensitivity and toxicity. In addition, changes in the enzymatic activities and metabolite levels during the treatment were analyzed. In a cohort (N = 236) of pediatric ALL patients enrolled in the Dutch ALL-9 protocol, we studied the enzymes inosine-5'-monophosphate dehydrogenase (IMPDH), thiopurine S-methyltransferase (TPMT), hypoxanthine guanine phosphoribosyl transferase (HGPRT), and purine nucleoside phosphorylase (PNP) as well as thioguanine nucleotides (TGN) and methylthioinosine nucleotides (meTINs). Activities of selected enzymes and levels of 6MP derivatives were measured at various time points during the course of therapy. The data obtained and the toxicity related parameters available for these patients were correlated with each other. We found several interesting relations, including high concentrations of two active forms of 6MP-TGN and meTIN-showing a trend toward association with better in vitro antileukemic effect of 6MP. High concentrations of TGN and elevated activity of HGPRT were found to be significantly associated with grade III/IV leucopenia. However, a lot of data of enzymatic activities and metabolite concentrations as well as clinical toxicity were missing, thereby limiting the number of assessed relations. Therefore, although a complex study of 6MP metabolism in ALL patients is feasible, it warrants more robust and strict data collection in order to be able to draw more reliable conclusions.
    Nucleosides Nucleotides &amp Nucleic Acids 04/2014; 33(4-6):422-433. · 0.71 Impact Factor
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    ABSTRACT: The most important reason for childhood cancer treatment failure in low-income countries is treatment abandonment. The aim of this study was to explore reasons for childhood cancer treatment abandonment and assess the clinical condition of these children. This was a descriptive study using semistructured questionnaires. Home visits were conducted to interview families of childhood cancer patients, diagnosed between January 2007 and January 2009, who had abandoned treatment at the Moi Teaching and Referral Hospital (MTRH). Between January 2007 and January 2009, 222 children were newly diagnosed with a malignancy at MTRH. Treatment outcome was documented in 180 patients. Of these 180 patients, 98 (54%) children abandoned treatment. From December 2011 until August 2012, 53 (54%) of the 98 families were contacted. Due to lack of contact information, 45 families were untraceable. From 53 contacted families, 46 (87%) families agreed to be interviewed. Reasons for abandonment were reported by 26 families, and they were diverse. Most common reasons were financial difficulties (46%), inadequate access to health insurance (27%) and transportation difficulties (23%). Most patients (72%) abandoned treatment after the first 3 months had been completed. Of the 46 children who abandoned treatment, 9 (20%) were still alive: 6 (67%) of these children looked healthy and 3 (33%) ill. The remaining 37 (80%) children had passed away. Prevention of childhood cancer treatment abandonment requires improved access to health insurance, financial or transportation support, proper parental education, psychosocial guidance and ameliorated communication skills of healthcare providers.
    Archives of Disease in Childhood 03/2014; · 3.05 Impact Factor

Publication Stats

5k Citations
1,694.68 Total Impact Points

Institutions

  • 1991–2014
    • VU University Amsterdam
      • • Department of Neurosurgery
      • • Department of Pediatric Hematology/Oncology
      Amsterdamo, North Holland, Netherlands
  • 2013
    • Sydney Children's Hospital
      Sydney, New South Wales, Australia
  • 2012–2013
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2002–2013
    • VU University Medical Center
      • • Department of Pediatrics
      • • Department of Haematology
      Amsterdamo, North Holland, Netherlands
  • 2010–2012
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
    • Hannover Medical School
      • Department of Paediatric Haematology and Oncology
      Hannover, Lower Saxony, Germany
  • 2009–2012
    • Dutch Childhood Oncology Group
      Rotterdam, South Holland, Netherlands
    • Aarhus University Hospital
      • Department of Pediatrics
      Aarhus, Central Jutland, Denmark
  • 2011
    • Leiden University Medical Centre
      • Department of Pediatrics
      Leiden, South Holland, Netherlands
    • Massachusetts General Hospital
      • Department of Neurology
      Boston, MA, United States
  • 2008–2009
    • Charles University in Prague
      Praha, Praha, Czech Republic
    • Carl Gustav Carus-Institut
      Pforzheim, Baden-Württemberg, Germany
    • Università degli Studi di Milano-Bicocca
      Milano, Lombardy, Italy
  • 2005
    • Gesellschaft für Pädiatrische Onkologie und Hämatologie
      Muenster, North Rhine-Westphalia, Germany
  • 2004
    • University of Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2003
    • Kent Hospital
      Warwick, Rhode Island, United States
  • 1991–1995
    • University of Amsterdam
      • Department of Paediatrics
      Amsterdamo, North Holland, Netherlands
  • 1994
    • Post University
      Post, Texas, United States