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1. Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma

Author

Drechsel, K. C. E., Broer, S. L., Stoutjesdijk, F. S., Twisk, J. W. R., van den Berg, M. H., Lambalk, C. B., van Leeuwen, F. E., Overbeek, A., van den Heuvel-Eibrink, M. M., van Dorp, W., de Vries, A. C. H., Loonen, J. J., van der Pal, H. J., Kremer, L. C., Tissing, W. J., Versluys, B., Kaspers, G. J. L., van Dulmen-den Broeder, E., and Veening, M. A.

Published
2023
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12. Oncologie

Author

van den Heuvel-Eibrink, M. M., Tissing, W. J. E., Derksen-Lubsen, G., editor, Moll, H.A., editor, Oudesluys-Murphy, A.M., editor, Sprij, A.J., editor, Bolt-Wieringa, J.W., editor, van den Elzen, A.P.M., editor, Leeuwenburgh-Pronk, W.G., editor, Ropers, F.G., editor, and Verhoeven, J.J., editor

Published
2018
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15. Prevalence, risk factors and optimal way to determine overweight, obesity and morbid obesity, in the first Dutch cohort of 2,338 long-term survivors of childhood cancer: a DCCSS-LATER study

Author

Pluimakers, V G, primary, van Atteveld, J E, additional, de Winter, D T C, additional, Bolier, M, additional, Fiocco, M, additional, Nievelstein, R A J, additional, Janssens, G O R, additional, Bresters, D, additional, van der Heiden-van der Loo, M, additional, de Vries, A C H, additional, Louwerens, M, additional, van der Pal, H J, additional, Pluijm, S M F, additional, Ronckers, C M, additional, Versluijs, A B, additional, Kremer, L C M, additional, Loonen, J J, additional, van Dulmen-den Broeder, E, additional, Tissing, W J E, additional, van Santen, H M, additional, van den Heuvel-Eibrink, M M, additional, and Neggers, S J C M M, additional

Published
2023
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17. Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma

Author

Drechsel, K. C.E., Broer, S. L., Stoutjesdijk, F. S., Twisk, J. W.R., van den Berg, M. H., Lambalk, C. B., van Leeuwen, F. E., Overbeek, A., van den Heuvel-Eibrink, M. M., van Dorp, W., de Vries, A. C.H., Loonen, J. J., van der Pal, H. J., Kremer, L. C., Tissing, W. J., Versluys, B., Kaspers, G. J.L., van Dulmen-den Broeder, E., Veening, M. A., Drechsel, K. C.E., Broer, S. L., Stoutjesdijk, F. S., Twisk, J. W.R., van den Berg, M. H., Lambalk, C. B., van Leeuwen, F. E., Overbeek, A., van den Heuvel-Eibrink, M. M., van Dorp, W., de Vries, A. C.H., Loonen, J. J., van der Pal, H. J., Kremer, L. C., Tissing, W. J., Versluys, B., Kaspers, G. J.L., van Dulmen-den Broeder, E., and Veening, M. A.

Abstract

Purpose: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. Methods: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. Results: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. Conclusion:HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.

Published
2023

18. Prevalence, risk factors and optimal way to determine overweight, obesity and morbid obesity, in the first Dutch cohort of 2,338 long-term survivors of childhood cancer: a DCCSS-LATER study

Author

Unit Opleiding Aios, Orthopaedie Onderzoek, MS Radiologie, Child Health, MS Radiotherapie, Cancer, SCT patientenzorg, PMC Medisch specialisten, PMC Research, Klinische Fysica RT, Haematologie patientenzorg, Zorg en O&O, Endocrinologie patientenzorg, Brain, Speerpunt, In Vivo NMR ISI, Pluimakers, V G, van Atteveld, J E, de Winter, D T C, Bolier, M, Fiocco, M, Nievelstein, R A J, Janssens, G O R, Bresters, D, van der Heiden-van der Loo, M, de Vries, A C H, Louwerens, M, van der Pal, H J, Pluijm, S M F, Ronckers, C M, Versluijs, A B, Kremer, L C M, Loonen, J J, van Dulmen-den Broeder, E, Tissing, W J E, van Santen, H M, van den Heuvel-Eibrink, M M, Neggers, S J C M M, Unit Opleiding Aios, Orthopaedie Onderzoek, MS Radiologie, Child Health, MS Radiotherapie, Cancer, SCT patientenzorg, PMC Medisch specialisten, PMC Research, Klinische Fysica RT, Haematologie patientenzorg, Zorg en O&O, Endocrinologie patientenzorg, Brain, Speerpunt, In Vivo NMR ISI, Pluimakers, V G, van Atteveld, J E, de Winter, D T C, Bolier, M, Fiocco, M, Nievelstein, R A J, Janssens, G O R, Bresters, D, van der Heiden-van der Loo, M, de Vries, A C H, Louwerens, M, van der Pal, H J, Pluijm, S M F, Ronckers, C M, Versluijs, A B, Kremer, L C M, Loonen, J J, van Dulmen-den Broeder, E, Tissing, W J E, van Santen, H M, van den Heuvel-Eibrink, M M, and Neggers, S J C M M

Published
2023

19. Treatment and outcome of the Dutch Childhood Craniopharyngioma Cohort study; first results after centralization of care

Author

MS Radiotherapie, Cancer, MS Oogheelkunde, Brain, Endocrinologie patientenzorg, PMC Medisch specialisten, Neurochirurgen, Child Health, Van Schaik, J, Schouten-van Meeteren, A Y N, Vos-Kerkhof, E, Janssens, G O, Porro, G L, Fiocco, M, Bakker, B, Tissing, W J E, Hoving, E W, van Santen, H M, MS Radiotherapie, Cancer, MS Oogheelkunde, Brain, Endocrinologie patientenzorg, PMC Medisch specialisten, Neurochirurgen, Child Health, Van Schaik, J, Schouten-van Meeteren, A Y N, Vos-Kerkhof, E, Janssens, G O, Porro, G L, Fiocco, M, Bakker, B, Tissing, W J E, Hoving, E W, and van Santen, H M

Published
2023

20. Changes in thyroid function parameters 3 months after allogeneic and autologous hematopoietic stem cell transplantation in children

Author

Endocrinologie onderzoek, CDL Cluster Speciële Diagnostiek, Other research (not in main researchprogram), Cluster C, Endocrinologie, Child Health, PMC Medisch specialisten, Cancer, Brain, Endocrinologie patientenzorg, Lebbink, C A, Bresters, D, Tersteeg, J P B, van den Bos, C, Dierselhuis, M P, Lentjes, E G W M, Verrijn Stuart, A A, Fiocco, M, Tissing, W J E, van Santen, H M, Endocrinologie onderzoek, CDL Cluster Speciële Diagnostiek, Other research (not in main researchprogram), Cluster C, Endocrinologie, Child Health, PMC Medisch specialisten, Cancer, Brain, Endocrinologie patientenzorg, Lebbink, C A, Bresters, D, Tersteeg, J P B, van den Bos, C, Dierselhuis, M P, Lentjes, E G W M, Verrijn Stuart, A A, Fiocco, M, Tissing, W J E, and van Santen, H M

Published
2023

24. Resting energy expenditure in children at risk of hypothalamic dysfunction

Author

Van Schaik, J, primary, Burghard, M, additional, Lequin, M H, additional, van Maren, E A, additional, van Dijk, A M, additional, Takken, T, additional, Rehorst-Kleinlugtenbelt, L B, additional, Bakker, B, additional, Meijer, L, additional, Hoving, E W, additional, Fiocco, M, additional, Schouten-van Meeteren, A Y N, additional, Tissing, W J E, additional, and van Santen, H M, additional

Published
2022
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25. Support needs of Dutch young adult childhood cancer survivors

Author

PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, SCT patientenzorg, van Erp, L M E, Maurice-Stam, H, Kremer, L C M, Tissing, W J E, van der Pal, H J H, Beek, L, de Vries, A C H, van den Heuvel-Eibrink, M M, Versluys, B A B, van der Heiden-van der Loo, M, van Gorp, M, Huizinga, G A, Grootenhuis, M A, PMC Medisch specialisten, Speerpunt, Zorg en O&O, Child Health, SCT patientenzorg, van Erp, L M E, Maurice-Stam, H, Kremer, L C M, Tissing, W J E, van der Pal, H J H, Beek, L, de Vries, A C H, van den Heuvel-Eibrink, M M, Versluys, B A B, van der Heiden-van der Loo, M, van Gorp, M, Huizinga, G A, and Grootenhuis, M A

Published
2022

33. Development of a self-limiting model of methotrexate-induced mucositis reinforces butyrate as a potential therapy

Author

da Silva Ferreira, A R, van der Aa, S A J, Wehkamp, T, Wardill, H R, Ten Klooster, J P, Garssen, J, Harthoorn, L F, Hartog, A, Harmsen, H J M, Tissing, W J E, van Bergenhenegouwen, J, da Silva Ferreira, A R, van der Aa, S A J, Wehkamp, T, Wardill, H R, Ten Klooster, J P, Garssen, J, Harthoorn, L F, Hartog, A, Harmsen, H J M, Tissing, W J E, and van Bergenhenegouwen, J

Abstract

Gastrointestinal mucositis is a complication of anticancer treatment, with few validated in vitro systems suitable to study the complex mechanisms of mucosal injury. Therefore, we aimed to develop and characterize a chemotherapeutic-induced model of mucositis using 3D intestinal organoids. Organoids derived from mouse ileum were grown for 7 days and incubated with different concentrations of the chemotherapeutic agent methotrexate (MTX). Metabolic activity, citrulline levels and cytokine/chemokine production were measured to determine the optimal dosage and incubation time. The protective effects of folinic acid on the toxicity of MTX were investigated by pre-treating organoids with (0.0005-50 µg/mL) folinic acid. The impact of microbial-derived short-chain fatty acids was evaluated by supplementation with butyrate in the organoid model. MTX caused a dose-dependent reduction in cell metabolic activity and citrulline production that was salvaged by folinic acid treatment. Overall, MTX causes significant organoid damage, which can be reversed upon removal of MTX. The protective effect of folinic acid suggest that the organoids respond in a clinical relevant manner. By using the model for intervention, it was found that prophylactic treatment with butyrate might be a valuable strategy for prophylactic mucositis prevention.

Published
2021

34. Development of a self-limiting model of methotrexate-induced mucositis reinforces butyrate as a potential therapy

Author

Afd Pharmacology, Pharmacology, da Silva Ferreira, A R, van der Aa, S A J, Wehkamp, T, Wardill, H R, Ten Klooster, J P, Garssen, J, Harthoorn, L F, Hartog, A, Harmsen, H J M, Tissing, W J E, van Bergenhenegouwen, J, Afd Pharmacology, Pharmacology, da Silva Ferreira, A R, van der Aa, S A J, Wehkamp, T, Wardill, H R, Ten Klooster, J P, Garssen, J, Harthoorn, L F, Hartog, A, Harmsen, H J M, Tissing, W J E, and van Bergenhenegouwen, J

Published
2021

38. New national recommendations for the treatment of pediatric differentiated thyroid carcinoma in the Netherlands

Author

Lebbink, C A, primary, Dekker, B L, additional, Bocca, G, additional, Braat, A J A T, additional, Derikx, J P M, additional, Dierselhuis, M P, additional, de Keizer, B, additional, Kruijff, S, additional, Kwast, A B G, additional, van Nederveen, F H, additional, Nieveen van Dijkum, E J M, additional, Nievelstein, R A J, additional, Peeters, R P, additional, Terwisscha van Scheltinga, C E J, additional, Tissing, W J E, additional, van der Tuin, K, additional, Vriens, M R, additional, Zsiros, J, additional, van Trotsenburg, A S P, additional, Links, T P, additional, and van Santen, H M, additional

Published
2020
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42. The impact of maintenance therapy on sleep-wake rhythms and cancer-related fatigue in pediatric acute lymphoblastic leukemia

Author

Steur, L M H, Kaspers, G J L, van Someren, E J W, van Eijkelenburg, N K A, van der Sluis, I M, Dors, N, van den Bos, C, Tissing, W J E, Grootenhuis, M A, van Litsenburg, R R L, Steur, L M H, Kaspers, G J L, van Someren, E J W, van Eijkelenburg, N K A, van der Sluis, I M, Dors, N, van den Bos, C, Tissing, W J E, Grootenhuis, M A, and van Litsenburg, R R L

Abstract

PURPOSE: To assess the impact of maintenance therapy and the additional impact of dexamethasone treatment on cancer-related fatigue and sleep-wake rhythms in pediatric acute lymphoblastic leukemia (ALL) patients and to determine the association between these outcomes.METHODS: A national cohort of pediatric ALL patients (≥ 2 years) was included (± 1 year post-diagnosis). Patients receiving dexamethasone were assessed twice (assessment with and without dexamethasone). Actigraphy assessments were used to calculate sleep-wake outcomes with nonparametric methods. Cancer-related fatigue was assessed with the PedsQL Multidimensional Fatigue Scale. Sleep-wake rhythms and cancer-related fatigue were compared between patients participating in the assessment without dexamethasone and healthy children (linear regression) and between assessments with and without dexamethasone (mixed models). Using linear regression, associations between sleep-wake outcomes and cancer-related fatigue were determined during assessments with and without dexamethasone.RESULTS: Responses were collected for 125 patients (113 assessments with and 81 without dexamethasone). The sleep-wake rhythm was less stable (p = 0.03) and less robust (p = 0.01), with lower physical activity levels (p < 0.001) and higher cancer-related fatigue levels (p < 0.001) in ALL patients compared to healthy children. Physical activity was lower (p = 0.001) and cancer-related fatigue more severe (p ≤ 0.001) during assessments with dexamethasone compared to without dexamethasone. Sleep-wake outcomes were significantly associated with cancer-related fatigue during periods without dexamethasone, but not during periods with dexamethasone.CONCLUSION: Sleep-wake rhythms are disturbed, physical activity levels lower, and cancer-related fatigue levels higher during maintenance therapy. Interventions aimed to enhance sleep-wake rhythms during maintenance therapy could improve cancer-related fatigue. Familie

Published
2020

43. Sleep-wake rhythm disruption is associated with cancer-related fatigue in pediatric acute lymphoblastic leukemia

Author

Steur, L M H, Kaspers, G J L, Van Someren, E J W, Van Eijkelenburg, N K A, Van der Sluis, I M, Dors, N, Van den Bos, C, Tissing, W J E, Grootenhuis, M A, Van Litsenburg, R R L, Steur, L M H, Kaspers, G J L, Van Someren, E J W, Van Eijkelenburg, N K A, Van der Sluis, I M, Dors, N, Van den Bos, C, Tissing, W J E, Grootenhuis, M A, and Van Litsenburg, R R L

Abstract

STUDY OBJECTIVES: To compare sleep-wake rhythms, melatonin and cancer-related fatigue in pediatric patients with acute lymphoblastic leukemia (ALL) to healthy children and to assess the association between sleep-wake outcomes and cancer-related fatigue.METHODS: A national cohort of ALL patients (2-18 years) was included. Sleep-wake rhythms were measured using actigraphy and generated the following variables: Interdaily stability (IS): higher IS reflects higher stability; intradaily variability (IV): lower IV indicates less fragmentation; L5 and M10 counts: activity counts during the five least and ten most active hours, respectively; and relative amplitude (RA): the ratio of L5 and M10 counts (higher RA reflects a more robust rhythm). The melatonin metabolite, 6-sulfatoxymelatonin (aMT6s), was assessed in urine. Cancer-related fatigue was assessed with the PedsQL Multidimensional Fatigue Scale. Using regression models sleep-wake rhythms, aMT6s, and cancer-related fatigue were compared to healthy children and associations between sleep-wake outcomes and cancer-related fatigue were assessed in ALL patients.RESULTS: In total, 126 patients participated (response rate: 67%). IS, RA and M10 counts were lower in patients compared to healthy children (p<0.001). aMT6s levels were comparable to healthy children (p=0.425). Patients with ALL were more fatigued compared to healthy children (p<0.001). Lower IS, RA and M10 counts and higher IV were significantly associated with more parent-reported cancer-related fatigue. Associations between sleep-wake rhythms and self-reported cancer-related fatigue were not statistically significant.CONCLUSIONS: Sleep-wake rhythm impairment is associated with more cancer-related fatigue in pediatric ALL patients. Interventions aimed to improve sleep hygiene and encourage physical activity may reduce cancer-related fatigue.

Published
2020

44. Population Pharmacokinetics and Pharmacodynamics of Ciprofloxacin Prophylaxis in Pediatric Acute Lymphoblastic Leukemia Patients

Author

Zorg en O&O, PMC Medisch specialisten, SCT patientenzorg, Infection & Immunity, Child Health, Regenerative Medicine and Stem Cells, Speerpunt, Sassen, S D T, Mathôt, R A A, Pieters, R, van Westreenen, M, de Haas, V, Kaspers, G J L, van den Bos, C, Tissing, W J E, Te Loo, D M W W, Bierings, M B, van der Sluis, I M, Zwaan, C M, Zorg en O&O, PMC Medisch specialisten, SCT patientenzorg, Infection & Immunity, Child Health, Regenerative Medicine and Stem Cells, Speerpunt, Sassen, S D T, Mathôt, R A A, Pieters, R, van Westreenen, M, de Haas, V, Kaspers, G J L, van den Bos, C, Tissing, W J E, Te Loo, D M W W, Bierings, M B, van der Sluis, I M, and Zwaan, C M

Published
2020

45. Population Pharmacokinetics and Pharmacodynamics of Ciprofloxacin Prophylaxis in Pediatric Acute Lymphoblastic Leukemia Patients

Author

Sassen, S D T, primary, Mathôt, R A A, additional, Pieters, R, additional, de Haas, V, additional, Kaspers, G J L, additional, van den Bos, C, additional, Tissing, W J E, additional, te Loo, D M W W, additional, Bierings, M B, additional, van Westreenen, M, additional, van der Sluis, I M, additional, and Zwaan, C M, additional

Published
2019
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48. Population Pharmacokinetics and Pharmacodynamics of Ciprofloxacin Prophylaxis in Pediatric Acute Lymphoblastic Leukemia Patients.

Author

Sassen, S D T, Mathôt, R A A, Pieters, R, Haas, V de, Kaspers, G J L, Bos, C van den, Tissing, W J E, Loo, D M W W te, Bierings, M B, Westreenen, M van, Sluis, I M van der, and Zwaan, C M

Subjects
CANCER chemotherapy, CANCER patients, CIPROFLOXACIN, CULTURES (Biology), DRUG resistance in microorganisms, LONGITUDINAL method, LYMPHOBLASTIC leukemia, MEDICAL cooperation, MICROBIAL sensitivity tests, PREDNISONE, RESEARCH, RECEIVER operating characteristic curves, DESCRIPTIVE statistics, ANTIBIOTIC prophylaxis, PHARMACODYNAMICS, CHILDREN
Abstract

Background Ciprofloxacin is used as antimicrobial prophylaxis in pediatric acute lymphoblastic leukemia (ALL) to decrease infections with gram-negative bacteria. However, there are no clear guidelines concerning prophylactic dose. Aims To determine the pharmacokinetics and pharmacodynamics (PKPD) of ciprofloxacin prophylaxis in a pediatric ALL population. The effect of patient characteristics and antileukemic treatment on ciprofloxacin exposure, the area under the concentration time curve over minimal inhibitory concentration (AUC24/MIC) ratios, and emergence of resistance were studied. Methods A total of 615 samples from 129 children (0–18 years) with ALL were collected in a multicenter prospective study. A population pharmacokinetic model was developed. Microbiological cultures were collected prior to and during prophylaxis. An AUC24/MIC of ≥125 was defined as target ratio. Results A 1-compartment model with zero-order absorption and allometric scaling best described the data. No significant (P <.01) covariates remained after backward elimination and no effect of asparaginase or azoles were found. Ciprofloxacin AUC24 was 16.9 mg*h/L in the prednisone prophase versus 29.3 mg*h/L with concomitant chemotherapy. Overall, 100%, 81%, and 18% of patients at, respectively, MIC of 0.063, 0.125, and 0.25 mg/L achieved AUC24/MIC ≥ 125. In 13% of the patients, resistant bacteria were found during prophylactic treatment. Conclusion Ciprofloxacin exposure shows an almost 2-fold change throughout the treatment of pediatric ALL. Depending on the appropriateness of 125 as target ratio, therapeutic drug monitoring or dose adjustments might be indicated for less susceptible bacteria starting from ≥ 0.125 mg/L to prevent the emergence of resistance and reach required targets for efficacy. [ABSTRACT FROM AUTHOR]

Published
2020
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50. Reproductive intentions and use of reproductive health care among female survivors of childhood cancer

Author

Van Dijk, M., Van Den Berg, M. H., Overbeek, A., Lambalk, C. B., Van Den Heuvel-Eibrink, M. M., Tissing, W. J., Kremer, L. C., Van Der Pal, H. J., Loonen, J. J., Versluys, B., Bresters, D., Kaspers, G. J.L., Van Leeuwen, F. E., Van Dulmen-Den Broeder, E., Van Dijk, M., Van Den Berg, M. H., Overbeek, A., Lambalk, C. B., Van Den Heuvel-Eibrink, M. M., Tissing, W. J., Kremer, L. C., Van Der Pal, H. J., Loonen, J. J., Versluys, B., Bresters, D., Kaspers, G. J.L., Van Leeuwen, F. E., and Van Dulmen-Den Broeder, E.

Published
2018

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