Gertjan J L Kaspers

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (350)1979.79 Total impact

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    ABSTRACT: The first cohorts to survive childhood lymphoid malignancies treated with cranial irradiation are now aging into adulthood, and concerns are growing about the development of radiotherapy-induced cognitive deficits in the aging brain. These deficits are hypothesized to increase over time. Their impact on daily functioning of older survivors, and the accompanying need for interventions, should be anticipated. By describing a detailed profile of executive function deficits and their associations with age, specific targets for neuropsychological intervention can be identified. Fifty survivors of childhood lymphoid malignancies and 58 related controls were assessed with the Amsterdam Neuropsychological Tasks program. The survivors were on average 31.1 (4.9) years old, treated with 22.5 (6.8) Gy cranial irradiation, and examined on average 25.5 (3.1) years after diagnosis. The survivors showed significantly decreased response speed, irrespective of the task at hand. Furthermore, we found deficits in working memory capacity, inhibition, cognitive flexibility, executive visuomotor control, attentional fluctuations, and sustained attention. Older age was associated with poorer performance on executive visuomotor control and inhibition. On executive visuomotor control, 50% of female survivors performed more than 1.5 SD below average, versus 15.4% of male survivors. The combination of visuospatial working memory problems and decreasing executive visuomotor control could result in difficulty with learning new motor skills at older ages, like walking with a cane. Deterioration of executive control and inhibition may result in decreased behavioral and emotional regulation in aging survivors. Especially the deficiency in executive visuomotor control in female survivors should be considered for (prophylactic) intervention. ( JINS , 2015, 21 , 1–13)
    Journal of the International Neuropsychological Society 09/2015; DOI:10.1017/S1355617715000788 · 2.96 Impact Factor
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    ABSTRACT: Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML-supportive care-and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects.
    Journal of Clinical Oncology 08/2015; DOI:10.1200/JCO.2015.62.8289 · 18.43 Impact Factor
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    ABSTRACT: Use of complementary and alternative medicine (CAM) is common among patients with childhood cancer. Health-care providers (HCP) should address this need properly. Geographical and cultural differences seem likely. This study explores perspectives on CAM of HCP involved in the care of children with cancer in Netherlands and Indonesia. Health beliefs, components of CAM, encouraging or discouraging CAM, and knowledge about CAM were assessed. We conducted a cross-sectional study using semi-structured questionnaires at a Dutch and Indonesian academic hospital. A total of 342 HCP participated: 119 Dutch (response rate 80%) and 223 Indonesian (response rate 87%). Chemotherapy can cure cancer according to more Dutch than Indonesian HCP (87% vs. 53% respectively, P < 0.001). Combination of chemotherapy and CAM is the best way to cure cancer according to more Indonesian than Dutch HCP (45% vs. 25%, P < 0.001). Dutch and Indonesian HCP recommend and discourage CAM use differently. Most Dutch (77%) and Indonesian HCP (84%) consider their knowledge about CAM to be inadequate (P = ns). Fewer Dutch doctors than other HCP want to learn more about CAM (51% vs. 76%, P = 0.007), whereas there is no significant difference in eagerness to learn about CAM between Indonesian doctors (64%) and other HCP (72%). Indonesian HCP have more positive views about CAM than their Dutch colleagues. Both Dutch and Indonesian HCP consider their knowledge about CAM to be inadequate. Therefore, education programs about CAM tailored to the needs of HCP are recommended, knowing that CAM is used frequently. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 08/2015; DOI:10.1002/pbc.25689 · 2.39 Impact Factor
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    ABSTRACT: At the government, hospital, and health-care provider level, corruption plays a major role in health-care systems in Africa. The returns on health investments of international financial institutions, health organisations, and donors might be very low when mismanagement and dysfunctional structures of health-care systems are not addressed. More funding might even aggravate corruption. We discuss corruption and its effects on cancer care within the African health-care system in a sociocultural context. The contribution of high-income countries in stimulating corruption is also described. Corrupt African governments cannot be expected to take the initiative to eradicate corruption. Therefore, international financial institutions, health organisations, and financial donors should use their power to demand policy reforms of health-care systems in Africa troubled by the issue of corruption. These modifications will ameliorate the access and quality of cancer care for patients across the continent, and ultimately improve the outcome of health care to all patients. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 08/2015; 16(8):e394-404. DOI:10.1016/S1470-2045(15)00163-1 · 24.69 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):4437-4437. DOI:10.1158/1538-7445.AM2015-4437 · 9.33 Impact Factor
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    ABSTRACT: Background: Retinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1+/+MYCNA). There are controversies concerning the existence of molecular subtypes within RB1−/− retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling. Methods: Genome-wide mRNA expression profiling was performed on 76 primary human retinoblastomas. Expression profiling was complemented by genome-wide DNA profiling and clinical, histopathological, and ex vivo drug sensitivity data. Findings: RNA and DNA profiling identified major variability between retinoblastomas. While gene expression differences between RB1+/+MYCNA and RB1−/− tumors seemed more dichotomous, differences within the RB1−/− tumors were gradual. Tumors with high expression of a photoreceptor gene signature were highly differentiated, smaller in volume and diagnosed at younger age compared with tumors with low photoreceptor signature expression. Tumors with lower photoreceptor expression showed increased expression of genes involved in M-phase and mRNA and ribosome synthesis and increased frequencies of somatic copy number alterations. Interpretation: Molecular, clinical and histopathological differences between RB1−/− tumors are best explained by tumor progression, reflected by a gradual loss of differentiation and photoreceptor expression signature. Since copy number alterations were more frequent in tumors with less photoreceptorness, genomic alterations might be drivers of tumor progression. Research in context: Retinoblastoma is an ocular childhood cancer commonly caused by mutations in the RB1 gene. In order to determine optimal treatment, tumor subtyping is considered critically important. However, except for very rare retinoblastomas without an RB1 mutation, there are controversies as to whether subtypes of retinoblastoma do exist. Our study shows that retinoblastomas are highly diverse but rather than reflecting distinct tumor types with a different etiology, our data suggests that this diversity is a result of tumor progression driven by cumulative genetic alterations. Therefore, retinoblastomas should not be categorized in distinct subtypes, but be described according to their stage of progression.
    07/2015; 2(7):660-670. DOI:10.1016/j.ebiom.2015.06.022
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    ABSTRACT: Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblastic leukemia (ALL). However, drug resistance phenomena pose major obstacles to efficacious ALL chemotherapy. Moreover, clinically relevant molecular mechanisms underlying chemoresistance remain largely obscure. Several alterations in MTX metabolism, leading to impaired accumulation of this cytotoxic agent in tumor cells, have been classified as determinants of MTX resistance. However, the relation between MTX resistance and long-term clinical outcome of ALL has not been shown previously. We have collected clinical data for 235 childhood ALL patients, for whom samples taken at the time of diagnosis were also broadly characterized with respect to MTX resistance. This included measurement of concentrations of MTX polyglutamates in leukemic cells, mRNA expression of enzymes involved in MTX metabolism (FPGS, FPGH, RFC, DHFR, and TS), MTX sensitivity as determined by the TS inhibition assay, and FPGS activity. Herein we demonstrate that higher accumulation of long-chain polyglutamates of MTX is strongly associated with better overall (10-year OS: 90.6 vs 64.1 %, P = 0.008) and event-free survival (10-year EFS: 81.2 vs 57.6 %, P = 0.029) of ALL patients. In addition, we assessed both the association of several MTX resistance-related parameters determined in vitro with treatment outcome as well as clinical characteristics of pediatric ALL patients treated with MTX-containing combination chemotherapy. High MTX sensitivity was associated with DNA hyperdiploid ALL (P < 0.001), which was linked with increased MTX accumulation (P = 0.03) and elevated reduced folate carrier (RFC) expression (P = 0.049) in this subset of ALL patients. TEL-AML1 fusion was associated with increased MTX resistance (P = 0.023). Moreover, a low accumulation of MTX polyglutamates was observed in MLL-rearranged and TEL-AML1 rearranged ALL (P < 0.05). These findings emphasize the central role of MTX in ALL treatment thereby expanding our understanding of the molecular basis of clinical differences in treatment response between ALL individuals. In particular, the identification of patients that are potentially resistant to MTX at diagnosis may allow for tailoring novel treatment strategies to individual leukemia patients.
    Journal of Hematology & Oncology 05/2015; 8(1):61. DOI:10.1186/s13045-015-0158-9 · 4.81 Impact Factor
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    ABSTRACT: Unlabelled: Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In AML cells, EphB1 transcript was inversely correlated with EphB1 promoter methylation. The presence of EphB1 allowed EfnB1 ligand-mediated p53 DNA binding, leading to restoration of the DNA damage response (DDR) cascade by the activation of ATR, Chk1, p53, p21, p38, CDK1(tyr15), and Bax, and downregulation of HSP27 and Bcl2. Comparatively, reintroduction of EphB1 expression in EphB1-methylated AML cells enhanced the same cascade of ATR, Chk1, p21, and CDK1(tyr15), which consequently enforced programmed cell death. Interestingly, in pediatric AML samples, EphB1 peptide phosphorylation and mRNA expression were actively suppressed as compared with normal bone marrow, and a significant percentage of the primary AML specimens had EphB1 promoter hypermethylation. Finally, EphB1 repression associated with a poor overall survival in pediatric AML. Combined, the contribution of EphB1 to the DDR system reveals a tumor-suppressor function for EphB1 in pediatric AML. Implications: The tumor-suppressor function of EphB1 is clinically relevant across many malignancies, suggesting that EphB1 is an important regulator of common cancer cell transforming pathways.
    Molecular Cancer Research 05/2015; 13(6). DOI:10.1158/1541-7786.MCR-14-0660-T · 4.38 Impact Factor
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    ABSTRACT: Development of relapse remains a problem for further improvements in the survival of pediatric AML patients. While virtually all patients show a good response to initial treatment, more patients respond poorly when treated at relapse. The cellular characteristics of leukemic blast cells that allow survival of initial treatment, relapse development and subsequent resistance to salvage treatment remain largely elusive. Therefore, we studied if leukemic blasts at relapse biologically resemble their initial diagnosis counterparts. We performed microarray gene expression profiling on paired initial and relapse samples of 23 pediatric AML patients. In 11 out of 23 patients, gene expression profiles of initial and corresponding relapse samples end up in different clusters in unsupervised analysis, indicating altered gene expression profiles. In addition, shifts in type I/II mutational status were found in 5 of these 11 patients, while shifts were found in 3 of the remaining 12 patients. Although differentially expressed genes varied between patients, they were commonly related to hematopoietic differentiation, encompassed genes involved in chromatin remodeling and showed associations with similar transcription factors. The top five were CEBPA, GFI1, SATB1, KLF2 and TBP . In conclusion, the leukemic blasts at relapse are biologically different from their diagnosis counterparts. These differences may be exploited for further development of novel treatment strategies.
    PLoS ONE 04/2015; 10(4):e0121730. DOI:10.1371/journal.pone.0121730 · 3.23 Impact Factor
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    ABSTRACT: Placement of a totally implantable venous access device in children with cancer often leads to hypertrophic scars after its removal. This study investigates whether the use of silicone gel sheets has a beneficial effect on scar outcome in children with cancer. In a three-arm randomized controlled trial, the effects of use of silicone gel sheets for 2 and 6 months were assessed and compared with no intervention in children with cancer after removal of the totally implantable venous access device. Silicone gel sheets were first administered 14 days after surgery. The 1-year follow-up included measurements at seven time points. Next to scar size assessment, the modified Vancouver Scar Scale was used to assess scar outcome. Thirty-six children participated. For hypertrophy, no significant differences were found between the two intervention groups and the control group. However, at 1-year follow-up, the 2-month application group showed significantly smaller scars compared with the group receiving silicone gel sheet treatment for 6 months (p = 0.04), but not when compared with the control group (p = 0.22). Longitudinal multilevel analyses could not confirm these findings and showed no significant intervention effects on both outcomes. This study provides no strong evidence to support the use of silicone gel sheets after totally implantable venous access device removal in children with cancer. There seems to be a small benefit for scar width with application for 2 months. However, for hypertrophy, the scar outcome shows no significant difference between the control group and the 2-month and 6-month treatment groups. Therapeutic, I.
    Plastic and Reconstructive Surgery 04/2015; 135(4):1086-1094. DOI:10.1097/PRS.0000000000001053 · 2.99 Impact Factor
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    ABSTRACT: The purpose of this study is to explore the applicability of a psychosocial intervention in childhood cancer patients. This individualized structured psychosocial program to enhance social-emotional functioning and coping with disease-related effects includes six sessions for children and two sessions for parents. This program was part of a combined intervention with physical exercise. Questionnaires are used to evaluate completion of the psychosocial intervention, coping and satisfaction with the psychosocial intervention by patients and psychologists, and ranking of the individual topics by patients, parents, and psychologists. Of the 30 patients (mean age 13.0 (SD 3.0); 53.3 % male; 30 % still on treatment) who participated in the psychosocial intervention, two dropped out due to medical complications and one due to lack of time; 90 % completed the psychosocial intervention. Overall, patients liked participation in the intervention (4.2 on a 5-point scale; SD 0.8) and were positive about the psychologists (8.1 on a 10-point scale; SD 1.3). Psychologists rated the intervention on several points (e.g., clarity of the manual and content of the intervention), and mean scores ranged from 7.1 (SD 1.1) to 8.6 (SD 0.9) on 10-point scales. Minor adaptations were suggested by patients and psychologists, including customizing according to age and a more patient-tailored approach. This psychosocial intervention for childhood cancer patients appears to be applicable. Future studies need to establish whether this intervention combined with a physical exercise intervention actually improves psychosocial functioning of childhood cancer patients. When proven effective, this combined intervention can be offered to childhood cancer patients and may enhance their physical health and quality of life.
    Supportive Care Cancer 01/2015; DOI:10.1007/s00520-014-2576-6 · 2.36 Impact Factor
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    ABSTRACT: Over the past decade, the proteasome inhibitor bortezomib (Velcade) has not only gained a cornerstone position in the treatment of hematological malignancies, particularly multiple myeloma and mantle cell lymphoma, but also in experimental therapeutics of acute leukemia. However, the therapeutic efficacy of bortezomib is hampered by the emergence of acquired resistance, for which multifactorial mechanisms have been identified. This review summarizes the current status of the molecular mechanisms underlying resistance to proteasome inhibitors that emerged in preclinical therapeutic studies, and discusses these findings in the clinical perspective of novel therapeutic modalities of hematological malignancies. The specific topics that will be addressed in the current review include the recently established mechanisms of resistance to proteasome inhibitors: the role of constitutive and immunoproteasomes, mutations in proteasome subunits, unfolded protein response, XBP1 and MARCKS proteins, multidrug efflux transporters, aggresomes and autophagy, as well as the impact of pro-survival signaling pathways and bone marrow microenvironment. The growing knowledge of the determinants that confer bortezomib resistance and/or toxicity has provided the basis for the rational development of second generation proteasome inhibitors, some of which were recently approved or that are undergoing clinical evaluation as novel strategies to overcome bortezomib resistance as well as to enhance clinical therapeutic efficacy along with minimal side effects. Collectively, these combined approaches should enhance therapeutic efficacy and outcome in patients with hematological malignancies.
    Drug Resistance Updates 12/2014; 18. DOI:10.1016/j.drup.2014.12.001 · 9.12 Impact Factor
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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 12/2014; 61:2180-2184. DOI:10.1002/pbc.25138 · 2.39 Impact Factor
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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; · 1.90 Impact Factor
  • U Creutzig · J Semmler · G L Kaspers · D Reinhardt · M Zimmermann
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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 Pädiatrie 11/2014; 226(6/07):323-331. DOI:10.1055/s-0034-1385918 · 1.06 Impact Factor
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    ABSTRACT: Objectives: Relapsed/refractory pediatric AML has a poor prognosis despite salvage therapy including stem-cell transplantation. Chemotherapy using FLAG plus liposomal daunorubicine (FLAG-DNX) is currently considered the standard in 1strelapse in Europe. FLAG is based on potentiation of cytarabine (Ara-C) by fludarabine (Flu) by increasing Ara-CTP levels. Clofarabine (CLO) is a novel purine nucleoside analog, designed to have improved efficacy. Methods: We initiated an ongoing phase 1B dose-escalation study using a '3 × 3 design' to define the optimal dose of CLO, replacing FLU in FLAG-DNX. Dosages consisted of Ara-C 2gr/m2/day (day 1-5), with escalation of DNX from 40, 60 to 80 mg/m2/day (day 1, 3 and 5), and CLO from 20, 30 to 40 mg/m2/day (day 1-5) in 5 dose-levels, without GCSF priming. At day 6 intrathecal Ara-C was administered. Serum and CSF were collected for pharmacokinetics (PK). CLO plasma and CSF concentrations were analyzed using LC-MS/MS. Results: We report safety and PK data on all dose levels after accrual of 33 AML patients. Patients were treated at 5 dose-levels (DL). Updated results and DLTs will be presented at the meeting. PK samples were available from 19 patients. At day 1 the median AUC was 28 ng/ (range 6-401), with a mean T1/2 of 1.5 hrs. Day 1 and day 5 results were similar. CSF levels were not measurable in most patients and were 0.1-0.2 ng/ in the 3 patients with detectable levels. Conclusions: The RP2D of CLO in a CLARA/DNX course in relapsed/refractory pediatric AML is 40 mg/m2, excluding patients with evidence of prior subclinical aspergillus. There is no evidence for PK interaction between CLO and the other drugs. We are currently testing the safety of an augmented dose of DNX (80 mg/m2) in 1strelapse AML patients (n = 4). Reponses are centrally reviewed and will be disclosed at the meeting.
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    ABSTRACT: Purpose: Our study explores socioeconomic, treatment-related, and psychological experiences of parents during cancer treatment of their children at an academic hospital in Kenya. Methods: This cross-sectional study used semi-structured questionnaires. Parents whose children came for cancer treatment consecutively between November 2012 and April 2013 were interviewed. Results: Between 2012 and 2013, 115 oncology patients attended the hospital and 75 families (response rate 65 %) were interviewed. Cancer treatment resulted in financial difficulties (89 %). More information about cancer and treatment was required (88 %). More contact with doctors was needed (83 %). At diagnosis, cancer was perceived as curable (63 %). However, parents were told by health-care providers that most children with cancer die (49 %). Parents had difficulties with understanding doctors' vocabulary (48 %). Common reasons to miss hospital appointments were travel costs (52 %) and hospital costs (28 %). Parents (95 %) used complementary alternative treatment (CAM) for their children. Health-care providers told parents not to use CAM (49 %). Parents had not discussed their CAM use with doctors (71 %). Community members isolated families because their child had cancer (25 %), believed that child was bewitched (57 %), advised to use CAM (61 %), and stopped conventional treatment (45 %). Some families (15 %) never disclosed the child's illness to community members. Parents shared experiences with other parents at the ward (97 %) and would otherwise not understand the disease and its treatment (87 %). Conclusions: Parents suffer financial hardships and are dissatisfied with doctors' communication regarding their children's condition. CAM is very commonly used. Doctors need to improve their communication skills and discuss CAM more openly. Cancer programs should include more support for parents: financial assistance, a facility where parents and children can stay during the course of therapy, and parent support groups.
    Supportive Care in Cancer 10/2014; 23(5). DOI:10.1007/s00520-014-2475-x · 2.36 Impact Factor
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    ABSTRACT: Lymphomatoid granulomatosis (LG) is a B-cell type lymphoproliferative disease. It mainly affects the lungs but may have extrapulmonary manifestations, especially in the central nervous system. The purpose of this study was to review the pediatric cases in the literature and add 2 new cases to the existing literature. A review of the literature was performed on children (0 to 18 years of age at diagnosis) with pathologically proven LG. We found 47 case reports, which, together with 2 new cases, were systematically analyzed. The median age was 12 years. The main symptoms were general, pulmonary, and neurological. Approximately one third of the patients were immunocompromised. High mortality rate was observed. Pediatric LG is a rare disease, which appears to be more frequently seen in immunocompromised patients, especially patients with leukemia. The disease has a high mortality rate; therefore, aggressive therapy according to a high-grade B-cell lymphoma protocol is justified.
    Journal of Pediatric Hematology/Oncology 10/2014; 36(7). DOI:10.1097/MPH.0000000000000090 · 0.90 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):LB-169-LB-169. DOI:10.1158/1538-7445.AM2014-LB-169 · 9.33 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):4764-4764. DOI:10.1158/1538-7445.AM2014-4764 · 9.33 Impact Factor

Publication Stats

6k Citations
1,979.79 Total Impact Points


  • 2002–2015
    • VU University Medical Center
      • • Department of Clinical Genetics
      • • Department of Pediatrics
      • • Department of Haematology
      Amsterdamo, North Holland, Netherlands
    • Karmanos Cancer Institute
      Detroit, Michigan, United States
  • 1993–2014
    • VU University Amsterdam
      • • Department of Pediatric Hematology/Oncology
      • • Department of Medical Oncology
      Amsterdamo, North Holland, Netherlands
  • 2013
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
    • National Heart, Lung, and Blood Institute
      • Hematology Branch
      Maryland, United States
  • 2006–2013
    • Dutch Childhood Oncology Group
      Rotterdam, South Holland, Netherlands
  • 2011
    • Leiden University Medical Centre
      • Department of Pediatrics
      Leiden, South Holland, Netherlands
  • 2010
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2009
    • Aarhus University Hospital
      • Department of Pediatrics
      Aarhus, Central Jutland, Denmark
    • University of Groningen
      Groningen, Groningen, Netherlands
    • St. Jude Medical
      Little Canada, Minnesota, United States
  • 2008–2009
    • Charles University in Prague
      Praha, Praha, Czech Republic
    • Università degli Studi di Milano-Bicocca
      Milano, Lombardy, Italy
  • 2004
    • University of Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2003
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
    • Kent Hospital
      Warwick, Rhode Island, United States
  • 1999–2002
    • University of Hamburg
      Hamburg, Hamburg, Germany
  • 2001
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 1993–2000
    • University of Amsterdam
      • Department of Paediatrics
      Amsterdamo, North Holland, Netherlands
  • 1995
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 1994
    • Post University
      Post, Texas, United States