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Body composition and bone density during
and after childhood cancer treatment
The flip side of therapy

Marissa Anna Hermina den Hoed

Body composition and bone density during and after childhood cancer therapy: The flip side of therapy
PhD thesis with a summary in Dutch, Utrecht University, The Netherlands
Paediatric Oncology, Princess Maxima Centre for paediatric Oncology, Division Wilhelmina Childrens’s Hospital,
University Medical Centre Utrecht
© Marissa A.H. den Hoed, Utrecht, 2017
All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without
prior written permission from the author. The copyright of the papers that have been published or have been
accepted for publication has been transferred to the respective journals.
Cover and Chapters
Lay-out

Printed by
ISBN


Marissa den Hoed (inspired on art of Axel Oswith)
Marissa den Hoed
Optima Grafische Communicatie, Rotterdam
978-90-393-6766-7

Body composition and bone density
during and after childhood cancer therapy
The flip side of therapy

Lichaamssamenstelling en botdichtheid
gedurende en na behandeling van kinderkanker
De keerzijde van behandeling

(met een samenvatting in het Nederlands)

Proefschrift
ter verkrijging van de graad van doctor aan de Universiteit Utrecht
op gezag van de rector magnificus, prof. dr. G.J. van der Zwaan,
ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen
op donderdag 17 mei 2017 des middags te 12:45 uur
door
Marissa Anna Hermina den Hoed
geboren op 8 augustus 1990
te Leiden

Promotoren:


Prof. dr. M.M. van den Heuvel-Eibrink
Prof. dr. R. Pieters

Copromotor: Dr. S.M.F. Pluijm

Contents
10

Chapter 1

General introduction and outline of this thesis

PART I

SIDE EFFECTS OF TREATMENT

Chapter 2

Genetic and metabolic determinants of methotrexate-induced
mucositis in paediatric acute lymphoblastic leukaemia

24

Chapter 3

The negative impact of being underweight and weight loss on
survival of children with acute lymphoblastic leukaemia

54

Chapter 4

Aggravated bone density decline following symptomatic
osteonecrosis in children with acute lymphoblastic leukaemia

78

Chapter 5

Bone mineral density in adult survivors of childhood cancer:
a literature review

96

Chapter 6

Bone mineral density after childhood cancer in 346 long-term adult
survivors of childhood cancer

120

Chapter 7

Genetic variation and bone mineral density in long-term adult
survivors of childhood cancer

138

Chapter 8

Catch-up of Bone Mineral Density Among Long-Term Survivors of
Childhood Cancer? Letter to the Editor: Response to the Article of
Gurney et al. 2014

158

PART II

EPILOGUE

Chapter 9

Summary

164

Chapter 10

Discussion

170

PART III

ADDENDA
Summary in Dutch (Nederlandse samenvatting)
Authors and affiliations
List of publications
Curriculum Vitae Auctoris
PhD portfolio
Acknowledgments (Dankwoord)
List of Abbreviations

186
190
192
194
195
198
202

Chapter 1
GENERAL INTRODUCTION AND
OUTLINE OF THIS THESIS


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