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1. A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma

Author

van Bladel, Diede A. G., Stevens, Wendy B. C., Kroeze, Leonie I., de Groen, Ruben A. L., de Groot, Fleur A., van der Last-Kempkes, Jessica L. M., Berendsen, Madeleine R., Rijntjes, Jos, Luijks, Jeroen A. C. W., Bonzheim, Irina, van der Spek, Ellen, Plattel, Wouter J., Pruijt, Johannes F. M., de Jonge-Peeters, Susan D. P. W. M., Velders, Gerjo A., Lensen, Chantal, van Bladel, Esther R., Federmann, Birgit, Hoevenaars, Brigiet M., Pastorczak, Agata, van der Werff ten Bosch, Jutte, Vermaat, Joost S. P., Nooijen, Peet T. G. A., Hebeda, Konnie M., Fend, Falko, Diepstra, Arjan, van Krieken, J Han J. M., Groenen, Patricia J. T. A., van den Brand, Michiel, and Scheijen, Blanca

Published
2023
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3. A multicentric, randomized, controlled clinical trial to study the impact of bedside model-informed precision dosing of vancomycin in critically ill children—BENEFICIAL trial.

Author

De Cock, Pieter A., Colman, Roos, Amza, Anca, De Paepe, Peter, De Pla, Hans, Vanlanduyt, Lieselot, Van der Linden, Dimitri, Schelstraete, Petra, Cools, Filip, Clarysse, Alexander, Debouver, Phebe, Biarent, Dominique, Vens, Daphne Vania, Smits, Anne, Godart, Valerie, Vanhaesebrouck, Sophie, Dhont, Evelyn, Bordon, Victoria, Mauel, Reiner, and Van Der Werff Ten Bosch, Jutte

Subjects
CRITICALLY ill children, DRUG monitoring, PEDIATRIC intensive care, NEONATAL intensive care, ACUTE kidney failure
Abstract

Background : Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration–time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children. Methods: Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400–600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400–600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality. Discussion: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children. Trial registration: Eudract number: 2019–004538-40. Registered on 2020–09-08 ClinicalTrials.gov NCT046666948. Registered on 2020–11-28 [ABSTRACT FROM AUTHOR]

Published
2024
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6. Long-term neurotoxicity among childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC Children Leukemia Group studies

Author

de Ville de Goyet, Maëlle, Kicinski, Michal, Suciu, Stefan, Vandecruys, Els, Uyttebroeck, Anne, Ferster, Alina, Freycon, Claire, Plat, Geneviève, Thomas, Caroline, Barbati, Mélissa, Dresse, Marie-Françoise, Paillard, Catherine, Pluchart, Claire, Simon, Pauline, Chantrain, Christophe, Minckes, Odile, van der Werff Ten Bosch, Jutte, Bertrand, Yves, Rohrlich, Pierre, Millot, Frédéric, Paulus, Robert, Benoît, Yves, Piette, Caroline, de Ville de Goyet, Maëlle, Kicinski, Michal, Suciu, Stefan, Vandecruys, Els, Uyttebroeck, Anne, Ferster, Alina, Freycon, Claire, Plat, Geneviève, Thomas, Caroline, Barbati, Mélissa, Dresse, Marie-Françoise, Paillard, Catherine, Pluchart, Claire, Simon, Pauline, Chantrain, Christophe, Minckes, Odile, van der Werff Ten Bosch, Jutte, Bertrand, Yves, Rohrlich, Pierre, Millot, Frédéric, Paulus, Robert, Benoît, Yves, and Piette, Caroline

Abstract

Survival after childhood acute lymphoblastic leukemia (ALL) has increased over the last 40 years with an overall survival above 90%. Survivors may experience neurological late effects secondary to chemotherapy and radiotherapy. This observational retrospective study evaluated the cumulative incidence of neurological late effects among 890 childhood ALL survivors treated in EORTC CLG trials (58741, 58831/2 and 58881) between 1971 and 1998. Median follow-up was 19 years and interquartile range of the follow-up was 15–22 years. At 20 years from the end of treatment, approximately 66% of patients from the 58741 trial (accrual time: 1971–1978) and approximately 15% from the more recent trials had cognitive disturbance grade 1 or higher. Cumulative incidences at 20 years from treatment end of seizures, stroke and leukoencephalopathy were respectively 45%, 16% and 62% in study 58741, 13%, 2% and 5% in study 58831/2, and 8%, 2% and 3% in study 58881. Patients who were 10–17 years of age at diagnosis had a higher incidence of stroke and leukoencephalopathy as compared to those less than 6 years of age. Noteworthy, all neurological late effects continued to occur beyond 5 years after end of treatment. This retrospective study highlights the frequency of neurological late effects in survivors of childhood ALL. With the increase of the overall survival of ALL patients, the role and potential benefit of longitudinal neurological screening should be evaluated in further studies as these neurological late effects become an important public health challenge. This study is part of the larger EORTC CLG 58 Late Adverse Effects (LAE) study (ClinicalTrials.gov Identifier NCT01298388, date of registration February 16, 2011)., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2024

9. Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis

Author

Drutman, Scott B., Haerynck, Filomeen, Zhong, Franklin L., Hum, David, Hernandez, Nicholas J., Belkaya, Serkan, Rapaport, Franck, de Jong, Sarah Jill, Creytens, David, Tavernier, Simon J., Bonte, Katrien, De Schepper, Sofie, van der Werff ten Bosch, Jutte, Lorenzo-Diaz, Lazaro, Wullaert, Andy, Bossuyt, Xavier, Orth, Gérard, Bonagura, Vincent R., Béziat, Vivien, Abel, Laurent, Jouanguy, Emmanuelle, Reversade, Bruno, and Casanova, Jean-Laurent

Published
2019

12. Diagnosis of IRAK-4-deficiency by flow cytometric measurement of IκB-α degradation.

Author

Frans, Glynis, Michiels, Birthe, Picard, Capucine, Ampofo, Louanne, Raes, Marc, Toelen, Jaan, Bucciol, Giorgia, van der Werff ten Bosch, Jutte, Moens, Leen, Wuyts, Greet, Dillaerts, Doreen, Casanova, Jean-Laurent, Schrijvers, Rik, Meyts, Isabelle, and Bossuyt, Xavier

Subjects
FLOW measurement, DYSPLASIA, MYELOID differentiation factor 88, DIAGNOSIS, NF-kappa B
Published
2024
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14. Randomized controlled trial on the effect of 1‐hour infusion of vincristine versus push injection on neuropathy in children with cancer (final analysis)

Author

Uittenboogaard, Aniek, primary, van den Berg, Marleen H., additional, Abbink, Floor C. H., additional, Twisk, Jos W. R., additional, van der Sluis, Inge M., additional, van den Bos, Cor, additional, van den Heuvel‐Eibrink, Marry M., additional, Segers, Heidi, additional, Chantrain, Christophe, additional, van der Werff ten Bosch, Jutte, additional, Willems, Leen, additional, Kaspers, Gertjan J. L., additional, and van de Velde, Mirjam Esther, additional

Published
2023
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16. Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype.

Author

Cockx, Maaike, Haerynck, Filomeen, Hoste, Levi, Schrijvers, Rik, Van der Werff ten Bosch, Jutte, Dillaerts, Doreen, Thomas, Debby, Schaballie, Heidi, Bucciol, Giorgia, Robberechts, Wiert, Patel, Dina, Berbers, Guy, Desombere, Isabelle, Geukens, Nick, Meyts, Isabelle, and Bossuyt, Xavier

Subjects
IMMUNOGLOBULINS, B cells, COMMON variable immunodeficiency, PRIMARY immunodeficiency diseases, ANTIBODY formation, CONJUGATED polymers, PNEUMOCOCCAL vaccines, POLYSACCHARIDES
Abstract

Antibody response on polysaccharide- and protein-based vaccines is useful to test B cell functionality. As only few studies have explored the value of studying immune response to both vaccines, we evaluated the clinical value of anti-polysaccharide and anti-protein Luminex-based multiplex assays in context of primary immunodeficiency (PID) diagnosis. A 10-plex Luminex-based assay detecting antibodies to ten pneumococcal polysaccharide (PnPS) serotypes [present in unconjugated Pneumovax, not in 13-valent pneumococcal conjugated vaccine (PCV)] and a 5-plex assay detecting antibodies to five protein antigens (present in DTap/Tdap) were clinically validated in healthy individuals (n=99) and in retrospective (n=399) and prospective (n=108) patient cohorts. Clinical features of individuals with impaired response to PnPS and/or proteins were compared to those with normal response. Antigen-specific antibody thresholds were determined in healthy individuals. Individuals with impaired anti-PnPS responses and deficient immunoglobulin levels suffered more from autoimmune diseases and had lower B cell levels compared to individuals with impaired anti-PnPS response with normal immunoglobulin levels. Individuals with combined impaired response to PnPS and proteins showed more severe clinical manifestations compared to individuals with isolated impaired response to PnPS or proteins. Eight of the 11 individuals with severely impaired responses to both PnPS and proteins had common variable immunodeficiency. Evaluation of the anti-PnPS response to four serotypes not contained in 20-valent PCV was comparable to evaluation to ten serotypes not contained in 13-valent PCV. Multiplexed assessment of anti-PnPS and anti-protein responses combined with immunoglobulin quantification provides useful clinical information to support PID diagnosis. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Randomized controlled trial on the effect of 1-hour infusion of vincristine versus push injection on neuropathy in children with cancer (final analysis)

Author

Uittenboogaard, Aniek, van den Berg, Marleen H., Abbink, Floor C.H., Twisk, Jos W.R., van der Sluis, Inge M., van den Bos, Cor, van den Heuvel-Eibrink, Marry M., Segers, Heidi, Chantrain, Christophe, van der Werff ten Bosch, Jutte, Willems, Leen, Kaspers, Gertjan J.L., van de Velde, Mirjam Esther, Uittenboogaard, Aniek, van den Berg, Marleen H., Abbink, Floor C.H., Twisk, Jos W.R., van der Sluis, Inge M., van den Bos, Cor, van den Heuvel-Eibrink, Marry M., Segers, Heidi, Chantrain, Christophe, van der Werff ten Bosch, Jutte, Willems, Leen, Kaspers, Gertjan J.L., and van de Velde, Mirjam Esther

Abstract

Introduction: Vincristine is an integral component of treatment for children with cancer. Its main dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1-hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short-term outcomes (median follow-up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1-hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow-up 20 months), which includes treatment outcome as a secondary objective (follow-up 3 years). Methods: VIPN was measured 1–7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed.Results: Forty-five participants per randomization group were included. There was no significant effect of 1-hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one-hour group (rate ratio 0.52, 95% confidence interval 0.33–0.80, p = 0.003). Four patients in the one-hour group and one patient in the push group relapsed. Two patients in the one-hour group died. Conclusion:1-hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1-hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile.

Published
2023

20. Correction:Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology: A Randomized Controlled Trial Comparing Push Injections with One-Hour Infusions (The VINCA Trial) (Cancers, (2020), 12, (3745), 10.3390/cancers12123745)

Author

van de Velde, Mirjam Esther, Kaspers, Gertjan J. L., Abbink, Floor C. H., Twisk, Jos W. R., van der Sluis, Inge M., van den Bos, Cor, van den Heuvel-Eibrink, Marry M., Segers, Heidi, Chantrain, Christophe, van der Werff ten Bosch, Jutte, Willems, Leen, van den Berg, Marleen H., Pediatrics, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, AII - Cancer immunology, Epidemiology and Data Science, APH - Health Behaviors & Chronic Diseases, and APH - Methodology

Abstract

Error in Table In the original publication, there was a mistake in Table 1 as published [1]. The number of patients with death was swapped between the one-hour administration group and the push administration group. The corrected Table 1 appears below. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.

Published
2023

22. Correction: van de Velde et al. Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology: A Randomized Controlled Trial Comparing Push Injections with One-Hour Infusions (The VINCA Trial). Cancers 2020, 12, 3745

Author

van de Velde, Mirjam Esther, primary, Kaspers, Gertjan J. L., additional, Abbink, Floor C. H., additional, Twisk, Jos W. R., additional, van der Sluis, Inge M., additional, van den Bos, Cor, additional, van den Heuvel-Eibrink, Marry M., additional, Segers, Heidi, additional, Chantrain, Christophe, additional, van der Werff ten Bosch, Jutte, additional, Willems, Leen, additional, and van den Berg, Marleen H., additional

Published
2023
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24. Quality of Life of Long‐term childhood Acute Lymphoblastic Leukemia survivors: Comparison with healthy controls

Author

Chantziara, Sofia, Musoro, Jammbe, Rowsell, Alison C., Sleurs, Charlotte, Coens, Corneel, Pe, Madeline, Suciu, Stefan, Kicinski, Michal, Missotten, Pierre, Vandecruys, Els, Uyttebroeck, Anne, Dresse, Marie‐françoise, Pluchart, Claire, Ferster, Alina, Freycon, Claire, Van Der Werff Ten Bosch, Jutte, Rohrlich, Pierre, Benoit, Yves, Darlington, Anne‐sophie, Piette, Caroline, And On Behalf Of The European Organisation For Research, and Group (clg, Treatment Of Cancer (eortc) Quality Of Life (qlg) And Childr

Abstract

Objective: Improved treatment landscape has led to better outcomes for paediatric acute lymphoblastic leukemia (ALL) survivors. As the number of survivors increase, we need to elucidate the long-term quality of life (QoL) and domains of complaints in these patients. Furthermore, the main priorities of these patients need to be clarified. We assessed long-term QoL outcomes of survivors of childhood ALL compared to matched population controls.Methods: QoL data were collected from survivors recruited in France and Belgium between 2012 and 2017, including the Short Form Health Survey (SF-12) and the Quality of Life Systemic Inventory (QLSI). The Wilcoxon test was used to compare SF-12 scale scores between survivors and matched population controls. For the QLSI, comparisons were mainly descriptive.Results: one hundred and eighty-six survivors (mean age: 27.6 years; range: 18.1–52.8) at follow-up completed QoL measures, amongst whom 180 were matched to controls. Overall, survivors had higher QoL on all SF12 scale scores, indicating that they had better functioning compared to controls. Statistically significant differences on the SF12 were observed for Vitality, Social Functioning, Role Limitations due to Emotional Problems and Mental Health scales. QLSI outcomes suggested that survivors were happier than controls with Couple and Social Relations. Controls were unhappiest compared to survivors with Money, Love life, Self-esteem, Nutrition and Paid Work.Conclusions: our findings suggest that survivors of childhood ALL have better QoL outcomes on some domains compared to the general population, specifically around social and emotional functioning, and that they tend to prioritize their relationships more. Interventions for improving QoL outcomes, might build on existing positive experiences with family, friends and partners.

Published
2022

25. Transient monosomy 7 is a rare event in young children with SAMD9L syndrome [Abstract]

Author

Andresen, Felicia, Sukova, Martina, Stary, Jan, De Mörloose, Barbara, Van Der Werff Ten Bosch, Jutte, Dworzak, Michael, Seidel, Markus G., Polychronopoulou, Sophia, Beier, Rita, Kratz, Christian P., Nathrath, Michaela, Frühwald, Michael C., Göhring, Gudrun, Bergmann, Anke K., Mayerhofer, Christina, Rotari, Natalia, Lebrecht, Dirk, Ramamoorthy, Senthilkumar, Yoshimi, Ayami, Strahm, Brigitte, Wlodarski, Marcin W., Niemeyer, Charlotte M., and Erlacher, Miriam

Subjects
ddc:610
Published
2022

26. Socio-economic outcomes among long-term childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC CLG studies: Results of the 58LAE study

Author

European Organisation for Research and Treatment of Cancer (EORTC) Children's Leukemia Group (CLG), Barbati, Melissa, Kicinski, Michal, Suciu, Stefan, Mazingue, Françoise, Vandecruys, Els, Plat, Geneviève, Uyttebroeck, Anne, Paillard, Catherine, Dresse, Marie-Françoise, Simon, Pauline, Pluchart, Claire, Minckes, Odile, Ferster, Alina, Freycon, Claire, Millot, Frederic, Van Der Werff Ten Bosch, Jutte, Chantrain, Christophe, Paulus, Robert, de Schaetzen, Gaetan, Rossi, Giovanna, Rohrlich, Pierre, Benoit, Yves, Piette, Caroline, Brussels Heritage Lab, and Growth and Development

Subjects
Adult, Employment, Marital Status, hematology, oncology, Humans, Pediatrics, Perinatology, and Child Health, Survivors, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Cranial Irradiation, Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
Abstract

OBJECTIVE: The objective of this study is to evaluate the socio-economic outcomes of survivors of childhood acute lymphoblastic leukaemia (ALL). METHODS: Childhood ALL adult survivors, enrolled in EORTC trials between 1971 and 1998 in France and Belgium, were invited to fill out a questionnaire with information about their socio-economic situation (living with a partner, having a university degree, having a job, working part time and history of having a paid job). The outcomes were compared with two matched control populations. RESULTS: Among 1418 eligible patients, 507 (35.8%) participated, including 39 (8%) and 61 (12%) patients who received a haematopoietic stem cell transplantation (HSCT) and a cranial radiotherapy (CRT), respectively. The median time to follow-up was 20 years, and median age was 25 years. Survivors showed a socio-economic level at least as good as controls. HCST and CRT were associated with a higher probability of not obtaining a bachelor degree (respectively OR = 3.49, 95% CI: 1.46-8.35 and OR = 2.31, 95% CI: 1.04-5.15), HSCT was associated with unemployment (OR = 2.89, 95% CI: 1.09-7.65) and having a relapse was associated with a higher probability of not having a partner (OR = 1.88, 95% CI: 1.01-3.51) adjusting for confounders. CONCLUSION: Childhood ALL survivors showed a high level of socio-economic participation. HCST and CRT were associated with poorer functioning.

Published
2022

27. The Effect of Robot-Led Distraction during Needle Procedures on Pain-Related Memory Bias in Children with Chronic Diseases: A Pilot and Feasibility Study

Author

Rheel, Emma, primary, Vervoort, Tine, additional, Malfliet, Anneleen, additional, van der Werff ten Bosch, Jutte, additional, Debulpaep, Sara, additional, Robberechts, Wiert, additional, Maes, Evelyn, additional, Mostaqim, Kenza, additional, Noel, Melanie, additional, and Ickmans, Kelly, additional

Published
2022
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28. Transient Monosomy 7 Is a Rare Event in Young Children with SAMD9L Syndrome

Author

Andresen, Felicia, primary, Sukova, Martina, additional, Stary, Jan, additional, De Moerloose, Barbara, additional, Van Der Werff Ten Bosch, Jutte, additional, Dworzak, Michael, additional, Seidel, Markus G, additional, Polychronopoulou, Sophia, additional, Beier, Rita, additional, Kratz, Christian P., additional, Nathrath, Michaela, additional, Frühwald, Michael C., additional, Göhring, Gudrun, additional, Bergmann, Anke K., additional, Mayerhofer, Christina, additional, Rotari, Natalia, additional, Lebrecht, Dirk, additional, Ramamoorthy, Senthilkumar, additional, Yoshimi, Ayami, additional, Strahm, Brigitte, additional, Wlodarski, Marcin W, additional, Niemeyer, Charlotte M., additional, and Erlacher, Miriam, additional

Published
2022
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30. Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea

Author

Petersen, Britt-Sabina, August, Dietrich, Abt, Renate, Alddafari, Moudjahed, Atarod, Lida, Baris, Safa, Bhavsar, Hemant, Brinkert, Florian, Buchta, Mary, Bulashevska, Alla, Chee, Ronnie, Cordeiro, Ana I., Dara, Naghi, Dückers, Gregor, Elmarsafy, Aisha, Frede, Natalie, Galal, Nermeen, Gerner, Patrick, Glocker, Erik-Oliver, Goldacker, Sigune, Hammermann, Jutta, Hasselblatt, Peter, Havlicekova, Zuzana, Hübscher, Katrin, Jesenak, Milos, Karaca, Neslihan E., Karakoc-Aydiner, Elif, Kharaghani, Mahboubeh M., Kilic, Sara S., Kiykim, Ayca, Klein, Christoph, Klemann, Christian, Kobbe, Robin, Kotlarz, Daniel, Laass, Martin W., Leahy, T. Ronan, Mesdaghi, Mehrnaz, Mitton, Sally, Neves, João F., Öztürk, Birol, Pereira, Luis F., Rohr, Jan, Restrepo, Jessica L. R., Ruzaike, Gunda, Saleh, Nadia, Seneviratne, Suranjith, Senol, Ebru, Speckmann, Carsten, Tegtmeyer, Daniel, Thankam, Paul, van der Werff ten Bosch, Jutte, von Bernuth, Horst, Zeissig, Sebastian, Zeissig, Yvonne, Franke, Andre, and Grimbacher, Bodo

Published
2017
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31. Gonadal development and function after high-risk gonadotoxic treatment and immature testicular tissue banking

Author

Braye, Aude, Van Der Werff Ten Bosch, Jutte, Gies, Inge, Ferster, Alina, Goossens, Ellen, Basic (bio-) Medical Sciences, Faculty of Medicine and Pharmacy, Biology of the Testis, Growth and Development, Clinical sciences, and Pediatrics

Abstract

Study question What is the long-term impact of a high-risk gonadotoxic treatment and a testicular biopsy procedure on the gonadal development and function of pre- and pubertal boys? Summary answer There is a risk for impaired reproductive hormone levels after high-risk gonadotoxic treatment protocols, especially after conditioning therapy before hematopoietic stem cell transplantation. What is known already Experimental fertility preservation programs have been started to safeguard the future fertility of pre- and pubertal boys requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies on their gonadal development and function are rather limited. Study design, size, duration A two-center follow-up study, conducted between 2002 and 2020, evaluated the gonadal development and function of pre- and pubertal boys who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of a high-risk gonadotoxic treatment and the testicular biopsy procedure. Participants/materials, setting, methods A cohort of 60 pre- and pubertal boys without ongoing spermatogenesis and requiring HR-C/R or CT-HSCT were included. Exclusion criteria were testicular cancer diagnosis and hormonal substitution treatment. Testicular growth measured with a Prader orchidometer and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and inhibin B (INHB) were analyzed after treatment completion and compared between HR-C/R and CT-HSCT treatment protocols as well as between boys accepting TTB and those refusing TTB. Main results and the role of chance Of the 60 pre- and pubertal boys included, 26 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted by 39 boys and refused by 21 boys. Most boys were prepubertal at diagnosis (87%), at treatment completion (78%) and at TTB (79%). After 5.0 (1.0-11.0) years post-treatment, most patients had normal testicular volumes (86%) and normal LH (81%), FSH (81%), testosterone (70%) and INHB (65%) serum levels. Testicular growth (P = 0.3773), LH (P = 0.4844), FSH (P = 0.1613) and INHB (P = 0.2553) were not significantly different between the treatment groups, but significantly more abnormal testosterone serum levels (P = 0.0138) were recorded after CT-HSCT (43%) compared to HR-C/R (10%). TTB had no effect on testicular growth (P > 0.9999), LH (P = 0.7186), FSH (P > 0.9999) and INHB (P = 0.7074). A significant difference for testosterone was observed between the TTB groups (P = 0.0210), but no significant difference for testosterone or the other hormones was observed when comparing the effect of the biopsy procedure within each treatment group separately. The Spearman’s correlation test reveals a significant positive correlation between patients treated by CT-HSCT and patients having chosen for TTB (P 0.9999). Limitations, reasons for caution This clinical follow-up study included a low patient number and the follow-up period was rather limited. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings. Wider implications of the findings A more accurate understanding of the long-term impact of a high-risk gonadotoxic treatment and a testicular biopsy procedure on the gonadal development and function will allow better counseling of patients interested in fertility preservation and optimize selection of patients eligible for fertility preservation. Trial registration number not applicable Issue Section: Male and female fertility preservation PDF

Published
2022

32. Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients

Author

van de Velde, Mirjam E., primary, Uittenboogaard, Aniek, additional, Yang, Wenjian, additional, Bonten, Erik, additional, Cheng, Cheng, additional, Pei, Deqing, additional, van den Berg, Marleen H., additional, van der Sluis, Inge M., additional, van den Bos, Cor, additional, Abbink, Floor C. H., additional, van den Heuvel-Eibrink, Marry M., additional, Segers, Heidi, additional, Chantrain, Christophe, additional, van der Werff ten Bosch, Jutte, additional, Willems, Leen, additional, Evans, William E., additional, and Kaspers, Gertjan J. L., additional

Published
2022
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33. DECIPHERING THE NON-CODING RNA LANDSCAPE OF PEDIATRIC ACUTE MYELOID LEUKEMIA

Author

UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, Vanhooren, Jolien, Van Camp, Laurens, Depreter, Barbara, De jong, Martijn, Uyttebroeck, Anne, Van Damme, An, Dedeken, Laurence, Dresse,Marie-Francoise, Van der Werff ten Bosch, Jutte, Hofmans, Mattias, Philippe, Jan, De Moerloose, Barbara, Lammens, Tim, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, Vanhooren, Jolien, Van Camp, Laurens, Depreter, Barbara, De jong, Martijn, Uyttebroeck, Anne, Van Damme, An, Dedeken, Laurence, Dresse,Marie-Francoise, Van der Werff ten Bosch, Jutte, Hofmans, Mattias, Philippe, Jan, De Moerloose, Barbara, and Lammens, Tim

Abstract

DECIPHERING THE NON-CODING RNA LANDSCAPE OF PEDIATRIC ACUTE MYELOID LEUKEMIA

Published
2022

34. Deciphering the Non-Coding RNA Landscape of Pediatric Acute Myeloid Leukemia

Author

Vanhooren, Jolien, Van Camp, Laurens, Depreter, Barbara, de Jong, Martijn, Uyttebroeck, Anne, Van Damme, An, Dedeken, Laurence, Dresse, Marie-Françoise, van der Werff Ten Bosch, Jutte, Hofmans, Mattias, Philippé, Jan, De Moerloose, Barbara M J B., Lammens, Tim, Vanhooren, Jolien, Van Camp, Laurens, Depreter, Barbara, de Jong, Martijn, Uyttebroeck, Anne, Van Damme, An, Dedeken, Laurence, Dresse, Marie-Françoise, van der Werff Ten Bosch, Jutte, Hofmans, Mattias, Philippé, Jan, De Moerloose, Barbara M J B., and Lammens, Tim

Abstract

Pediatric acute myeloid leukemia (pedAML) is a heterogeneous blood cancer that affects children. Although survival rates have significantly improved over the past few decades, 20–30% of children will succumb due to treatment-related toxicity or relapse. The molecular characterization of the leukemic stem cell, shown to be responsible for relapse, is needed to improve treatment options and survival. Recently, it has become clear that non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a role in the development of human diseases, including pediatric cancer. Nevertheless, non-coding RNA expression data in pedAML are scarce. Here, we explored lncRNA (n = 30,168) and miRNA (n = 627) expression in pedAML subpopulations (leukemic stem cells (LSCs) and leukemic blasts (L-blasts)) and their normal counterparts (hematopoietic stem cells and control myeloblasts). The potential regulatory activity of differentially expressed lncRNAs in LSCs (unique or shared with the L-blast comparison) on miRNAs was assessed. Moreover, pre-ranked gene set enrichment analyses of (anti-) correlated protein-coding genes were performed to predict the functional relevance of the differentially upregulated lncRNAs in LSCs (unique or shared with the L-blast comparison). In conclusion, this study provides a catalog of non-coding RNAs with a potential role in the pathogenesis of pedAML, paving the way for further translational research studies., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2022

35. The BOOST paediatric advance care planning intervention for adolescents with cancer and their parents: development, acceptability and feasibility

Author

UMC Utrecht Holding, Palliatieve Zorg, Child Health, Cancer, JC onderzoeksprogramma Kanker, van Driessche, Anne, Gilissen, Joni, De Vleminck, Aline, Kars, Marijke, Fahner, Jurrianne, van der Werff ten Bosch, Jutte, Deliens, Luc, Cohen, Joachim, Beernaert, Kim, UMC Utrecht Holding, Palliatieve Zorg, Child Health, Cancer, JC onderzoeksprogramma Kanker, van Driessche, Anne, Gilissen, Joni, De Vleminck, Aline, Kars, Marijke, Fahner, Jurrianne, van der Werff ten Bosch, Jutte, Deliens, Luc, Cohen, Joachim, and Beernaert, Kim

Published
2022

37. Deciphering the Non-Coding RNA Landscape of Pediatric Acute Myeloid Leukemia

Author

Vanhooren, Jolien, primary, Camp, Laurens Van, additional, Depreter, Barbara, additional, de Jong, Martijn de, additional, Uyttebroeck, Anne, additional, Van Damme, An Van, additional, Dedeken, Laurence, additional, Dresse, Marie-Françoise, additional, van der Werff ten Bosch, Jutte van der Werff ten, additional, Hofmans, Mattias, additional, Philippé, Jan, additional, De Moerloose, Barbara De, additional, and Lammens, Tim, additional

Published
2022
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38. Consensus Recommendations for the Clinical Management of Hematological Malignancies in Patients with DNA Double Stranded Break Disorders

Author

Pastorczak, Agata, primary, Attarbaschi, Andishe, additional, Bomken, Simon, additional, Borkhardt, Arndt, additional, van der Werff ten Bosch, Jutte, additional, Elitzur, Sarah, additional, Gennery, Andrew R., additional, Hlavackova, Eva, additional, Kerekes, Arpád, additional, Křenová, Zdenka, additional, Mlynarski, Wojciech, additional, Szczepanski, Tomasz, additional, Wassenberg, Tessa, additional, and Loeffen, Jan, additional

Published
2022
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39. Fertility Status Among Long-Term Childhood Acute Lymphoblastic Leukaemia Survivors Enrolled Between 1971 and 1998 in EORTC CLG Studies: Results of the 58 Late Adverse Effects Study

Author

Rossi, Giovanna, primary, Kicinski, Michal, additional, Suciu, Stefan, additional, Vandecruys, Els, additional, Plat, Geneviève, additional, Uyttebroeck, Anne, additional, Paillard, Catherine, additional, Barbati, Mélissa, additional, Dresse, Marie-Françoise, additional, Simon, Pauline, additional, Minckes, Odile, additional, Pluchart, Claire, additional, Ferster, Alina, additional, Freycon, Claire, additional, Millot, Frederic, additional, van der Werff ten Bosch, Jutte, additional, Chantrain, Christophe, additional, Paulus, Robert, additional, de Rojas, Teresa, additional, de Schaetzen, Gaetan, additional, Rohrlich, Pierre, additional, Benoit, Yves, additional, and Piette, Caroline, additional

Published
2022
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40. Face-Validated Quality Indicators for Appropriateness Of End-Of-Life Care in Children With Serious Illness

Author

Piette, Veerle, Deliens, Luc, van der Werff ten Bosch, Jutte, Beernaert, Kim, Cohen, Joachim, Family Medicine and Chronic Care, Faculty of Medicine and Pharmacy, End-of-life Care Research Group, Clinical sciences, Growth and Development, and Pediatrics

Subjects
and Child Health, IMPACT, GENETIC-DISORDERS, Medicine and Health Sciences, PATTERNS, DEATH, YOUNG-PEOPLE, PEDIATRIC PALLIATIVE CARE, Pediatrics, Perinatology, CANCER
Abstract

OBJECTIVE: To develop and face-validate population-level indicators for potential appropriateness of end-of-life care, for children with cancer, neurological conditions, and genetic/congenital conditions, to be applied to administrative health data containing medication and treatment variables. STUDY DESIGN: Modified RAND/University of California at Los Angeles (RAND/UCLA) appropriateness method. We identified potential indicators per illness group through systematic literature review, scoping review, and expert interviews. Three unique expert panels, a cancer (n=19), neurology (n=21), and genetic/congenital (n=17) panel, participated in interviews and rated indicators in individual ratings, group discussions, and second individual ratings. Each indicator was rated on a scale from 1 to 9 for suitability. Consensus was calculated with Interpercentile Range Adjusted for Symmetry formula. Indicators with consensus about unsuitability were removed, those with consensus about suitability were retained, those withlack of consensus deliberated in the group discussion. Experts included pediatricians, nurses, psychologists, physiotherapists, pharmacologists, care coordinators, general practitioners, social workers from hospitals, care teams, and general practice. RESULTS: Literature review and expert interviews yielded 115 potential indicators for cancer, 111 for neurological conditions, and 99 for genetic/congenital conditions. We combined similar indicators, resulting in respectively 36, 32, and 33 indicators per group. Expert scoring approved 21 indicators for cancer, 24 for neurological conditions, and 23 for genetic/congenital conditions. CONCLUSIONS: Our indicators can be applied to administrative data to evaluate appropriateness of children's end-of-life care. Differences from adults' indicators stress the specificity of children's end-of-life care. Individual care and remaining aspects, such as family support, can be evaluated with complementary tools.

Published
2022

41. Deciphering the non-coding landscape of pediatric acute myeloid leukemia

Author

Vanhooren, Jolien, Van Camp, Laurens, Depreter, Barbara, de Jong, Martijn, Uyttebroeck, Anne, Van Damme, An, Dedeken, Laurence, Dresse, Marie-Françoise, van der Werff ten Bosch, Jutte, Hofmans, Mattias, Philippé, Jan, De Moerloose, Barbara, and Lammens, Tim

Subjects
Medicine and Health Sciences
Abstract

Pediatric acute myeloid leukemia (pedAML) is a heterogeneous blood cancer that affects children. Although survival rates have significantly improved over the past few decades, 20–30% of children will succumb due to treatment-related toxicity or relapse. The molecular characterization of the leukemic stem cell, shown to be responsible for relapse, is needed to improve treatment options and survival. Recently, it has become clear that non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a role in the development of human diseases, including pediatric cancer. Nevertheless, non-coding RNA expression data in pedAML are scarce. Here, we explored lncRNA (n = 30,168) and miRNA (n = 627) expression in pedAML subpopulations (leukemic stem cells (LSCs) and leukemic blasts (L-blasts)) and their normal counterparts (hematopoietic stem cells and control myeloblasts). The potential regulatory activity of differentially expressed lncRNAs in LSCs (unique or shared with the L-blast comparison) on miRNAs was assessed. Moreover, pre ranked gene set enrichment analyses of (anti-) correlated protein-coding genes were performed to predict the functional relevance of the differentially upregulated lncRNAs in LSCs (unique or shared with the L-blast comparison). In conclusion, this study provides a catalog of non-coding RNAs with a potential role in the pathogenesis of pedAML, paving the way for further translational research studies.

Published
2022

43. Additional file 1 of The BOOST paediatric advance care planning intervention for adolescents with cancer and their parents: development, acceptability and feasibility

Author

van Driessche, Anne, Gilissen, Joni, De Vleminck, Aline, Kars, Marijke, Fahner, Jurrianne, van der Werff ten Bosch, Jutte, Deliens, Luc, Cohen, Joachim, and Beernaert, Kim

Abstract

Additional file 1. Evolution of specifications and adaptations to the BOOST pACP intervention components.

Published
2022
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44. Additional file 3 of The BOOST paediatric advance care planning intervention for adolescents with cancer and their parents: development, acceptability and feasibility

Author

van Driessche, Anne, Gilissen, Joni, De Vleminck, Aline, Kars, Marijke, Fahner, Jurrianne, van der Werff ten Bosch, Jutte, Deliens, Luc, Cohen, Joachim, and Beernaert, Kim

Abstract

Additional file 3. Illustrative quotes from adolescents and parents who participated in the feasibility test (families n=3), on the BOOST pACP core components.

Published
2022
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45. Sociodemographic and Medical Determinants of Quality of Life in Long-Term Childhood Acute Lymphoblastic Leukemia Survivors Enrolled in EORTC CLG Studies

Author

Sleurs, Charlotte, primary, Musoro, Jammbe, additional, Rowsell, Ali, additional, Kicinski, Michal, additional, Suciu, Stefan, additional, Chantziara, Sofia, additional, Coens, Corneel, additional, Pe, Madeline, additional, Missotten, Pierre, additional, Vandecruys, Els, additional, Uyttebroeck, Anne, additional, Dresse, Marie-Françoise, additional, Pluchart, Claire, additional, Ferster, Alina, additional, Freycon, Claire, additional, van der Werff ten Bosch, Jutte, additional, Rohrlich, Pierre-Simon, additional, Benoit, Yves, additional, Darlington, Anne-Sophie, additional, and Piette, Caroline, additional

Published
2021
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46. JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia

Author

Boztug, Kaan, Järvinen, Päivi M, Salzer, Elisabeth, Racek, Tomas, Mönch, Sebastian, Garncarz, Wojciech, Gertz, E Michael, Schäffer, Alejandro A, Antonopoulos, Aristotelis, Haslam, Stuart M, Schieck, Lena, Puchałka, Jacek, Diestelhorst, Jana, Appaswamy, Giridharan, Lescoeur, Brigitte, Giambruno, Roberto, Bigenzahn, Johannes W, Elling, Ulrich, Pfeifer, Dietmar, Conde, Cecilia Domínguez, Albert, Michael H, Welte, Karl, Brandes, Gudrun, Sherkat, Roya, van der Werff ten Bosch, Jutte, Rezaei, Nima, Etzioni, Amos, Bellanné-Chantelot, Christine, Superti-Furga, Giulio, Penninger, Josef M, Bennett, Keiryn L, von Blume, Julia, Dell, Anne, Donadieu, Jean, and Klein, Christoph

Published
2014
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47. Fertility status among long-term childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC CLG studies: results of the 58 Late Adverse Effects study

Author

Rossi, Giovanna, primary, Kicinski, Michal, additional, Suciu, Stefan, additional, Vandecruys, Els, additional, Plat, Geneviève, additional, Uyttebroeck, Anne, additional, Paillard, Catherine, additional, Barbati, Mélissa, additional, Dresse, Marie-Françoise, additional, Simon, Pauline, additional, Minckes, Odile, additional, Pluchart, Claire, additional, Ferster, Alina, additional, Freycon, Claire, additional, Millot, Frederic, additional, van der Werff ten Bosch, Jutte, additional, Chantrain, Christophe, additional, Paulus, Robert, additional, de Rojas, Teresa, additional, de Schaetzen, Gaetan, additional, Rohrlich, Pierre, additional, Benoit, Yves, additional, and Piette, Caroline, additional

Published
2021
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48. The association between vincristine‐induced peripheral neuropathy and health‐related quality of life in children with cancer

Author

van de Velde, Mirjam E., primary, van den Berg, Marleen. H., additional, Kaspers, Gertjan J. L., additional, Abbink, Floor C. H., additional, Twisk, Jos W. R., additional, van der Sluis, Inge M., additional, van den Bos, Cor, additional, van den Heuvel‐Eibrink, Marry M., additional, Segers, Heidi, additional, Chantrain, Christophe, additional, van der Werff Ten Bosch, Jutte, additional, Willems, Leen, additional, and van Litsenburg, Raphaële R. L., additional

Published
2021
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49. Socio‐economic outcomes among long‐term childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC CLG studies: Results of the 58LAE study.

Author

Barbati, Melissa, Kicinski, Michal, Suciu, Stefan, Mazingue, Françoise, Vandecruys, Els, Plat, Geneviève, Uyttebroeck, Anne, Paillard, Catherine, Dresse, Marie‐Françoise, Simon, Pauline, Pluchart, Claire, Minckes, Odile, Ferster, Alina, Freycon, Claire, Millot, Frederic, Van Der Werff ten Bosch, Jutte, Chantrain, Christophe, Paulus, Robert, de Schaetzen, Gaetan, and Rossi, Giovanna

Subjects
LYMPHOBLASTIC leukemia prognosis, LYMPHOBLASTIC leukemia treatment, CANCER patient psychology, CONFIDENCE intervals, UNEMPLOYMENT, LYMPHOBLASTIC leukemia, TUMORS in children, PATIENTS' attitudes, COMPARATIVE studies, SOCIAL classes, QUESTIONNAIRES, DESCRIPTIVE statistics, EMPLOYMENT, RESEARCH funding, HEMATOPOIETIC stem cell transplantation, ODDS ratio, MARITAL status, STATISTICAL sampling, EDUCATIONAL attainment, ADULTS
Abstract

Objective: The objective of this study is to evaluate the socio‐economic outcomes of survivors of childhood acute lymphoblastic leukaemia (ALL). Methods: Childhood ALL adult survivors, enrolled in EORTC trials between 1971 and 1998 in France and Belgium, were invited to fill out a questionnaire with information about their socio‐economic situation (living with a partner, having a university degree, having a job, working part time and history of having a paid job). The outcomes were compared with two matched control populations. Results: Among 1418 eligible patients, 507 (35.8%) participated, including 39 (8%) and 61 (12%) patients who received a haematopoietic stem cell transplantation (HSCT) and a cranial radiotherapy (CRT), respectively. The median time to follow‐up was 20 years, and median age was 25 years. Survivors showed a socio‐economic level at least as good as controls. HCST and CRT were associated with a higher probability of not obtaining a bachelor degree (respectively OR = 3.49, 95% CI: 1.46–8.35 and OR = 2.31, 95% CI: 1.04–5.15), HSCT was associated with unemployment (OR = 2.89, 95% CI: 1.09–7.65) and having a relapse was associated with a higher probability of not having a partner (OR = 1.88, 95% CI: 1.01–3.51) adjusting for confounders. Conclusion: Childhood ALL survivors showed a high level of socio‐economic participation. HCST and CRT were associated with poorer functioning. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Additional file 2 of Advance care planning for adolescents with cancer and their parents: study protocol of the BOOST pACP multi-centre randomised controlled trial and process evaluation

Author

van Driessche, Anne, De Vleminck, Aline, Gilissen, Joni, Kars, Marijke C., van der Werff ten Bosch, Jutte, Deliens, Luc, Cohen, Joachim, and Beernaert, Kim

Abstract

Additional file 2. ‘Process evaluation methods based on UK MRC guidance on process evaluations of complex interventions (Moore et al., 2015)’. This table provides an overview of all process indicators that are evaluated in the process evaluation, including methods and at what timepoints.

Published
2021
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