{"id":10177,"date":"2026-04-09T09:06:11","date_gmt":"2026-04-09T09:06:11","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/rianne-van-lieshout\/"},"modified":"2026-04-23T07:41:58","modified_gmt":"2026-04-23T07:41:58","slug":"rianne-van-lieshout","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/rianne-van-lieshout\/","title":{"rendered":"Rianne Van Lieshout"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":12852,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-10177","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"Medical nutrition therapy in acute myeloid leukemia patients during intensive treatment","samenvatting":"Er is geen Nederlandse samenvatting beschikbaar. De Engelse samenvatting vind je <a href=\"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/rianne-van-lieshout\/\">hier<\/a>.","summary":"Acute myeloid leukemia (AML) is the most common acute leukemia subtype among adults, though it remains relatively rare, accounting for approximately 900 new diagnoses per year in the Netherlands (1). Myeloid dysplastic syndrome (MDS) is another rare hematological malignancy, with advanced subtypes requiring similar treatment to that of AML (2). The currently potentially available curative treatment for AML\/MDS involves intensive remission-induction treatment with one or two high-dose chemotherapy cycles, usually followed by a conditioning regimen and hematopoietic stem cell transplantation (HSCT) (3). Unfortunately, these treatments often cause severe gastrointestinal side effects that severely compromise patients\u2019 nutritional status (4-7). A deteriorated nutritional status during AML\/MDS treatment has been associated with decreased survival rates (7-13), increased relapse risk (7, 12, 14), more complications (8, 15, 16), prolonged hospital length of stay (8, 13, 17), higher fatigue levels (18), functional decline (6, 19) and reduced quality of life (18). To prevent malnutrition, current guidelines established by the European Societies for Clinical Nutrition and Metabolism (ESPEN) and for Blood and Marrow Transplantation (EBMT) recommend medical nutrition therapy (MNT) when nutritional intake becomes inadequate (5, 20, 21). These guidelines recommend enteral nutrition instead of parenteral nutrition as the first-choice MNT, unless severe gastrointestinal symptoms occur (5, 20, 21). However, nutritional support practices and adherence to these guidelines during intensive AML\/MDS treatment in the Netherlands have not yet been examined. To address this gap, the first aim of this thesis, explored in Chapter 2, was to gain insight into nutritional support practices, particularly the use of MNT, during intensive AML\/MDS treatment. In addition, this chapter aimed to identify the barriers and facilitators to adherence to the current nutritional guidelines during this treatment.\n\nChapter 2.1 describes a nationwide survey examining nutritional support practices and adherence to the ESPEN\/EBMT nutritional guidelines for AML\/MDS patients during intensive therapy across the 22 hospitals in the Netherlands that provide this treatment. As opposed to the recommendations in the ESPEN\/EBMT guidelines, the results of this survey indicated that nutritional support procedures were not incorporated into clinical care pathways for AML\/MDS patients in most hospitals, and that body composition assessments were performed inconsistently. However, the greatest discrepancy between guidelines and clinical practice involved the use of MNT. Although inadequate nutritional intake was the main indicator for starting MNT in most hospitals - consistent with the guidelines (5, 20, 21) - the criteria used to define inadequate intake and the timing for initiating MNT varied across treatment centers. Additionally, although a few hospitals adhered to the ESPEN\/EBMT recommendations by using enteral nutrition as the first-choice MNT, most hospitals still preferred parenteral nutrition. Moreover, one hospital followed a wait-and-see approach toward both forms of MNT, limiting its use to exceptional and severe cases only.\n\nChapters 2.2 and 2.3 describe the experiences and perspectives of health care professionals (HCPs) concerning MNT, as well as the barriers and facilitators that influenced their adherence to the ESPEN\/EBMT recommendation to prefer enteral over parenteral nutrition. Results indicated that HCPs, including hematology nurses and hematologists, considered MNT as an important component of supportive care for AML\/MDS patients undergoing intensive treatment. They believed that MNT is essential for maintaining adequate nutritional status, enabling patients to complete their treatment schedule without delays, and mitigating the negative physical and psychosocial consequences of the nutrition-related side effects. Furthermore, MNT often contributed positively to patients\u2019 well-being by alleviating the pressure to eat and reducing concerns about nutrient deficiencies. Nevertheless, contrary to the ESPEN\/EBMT guidelines, HCPs were reluctant or hesitant toward using enteral nutrition as the first-choice MNT and favored parenteral nutrition due to its ease of administration via an already in situ central venous catheter without gastrointestinal intolerance or physical discomfort. Barriers to the use of enteral nutrition included concerns about its feasibility and gastrointestinal tolerance, the discomfort and bleeding risks associated with feeding tubes, and patient refusals. Other major barriers involved the lack of nutritional knowledge among HCPs, lack of interprofessional collaboration, and the limited level of scientific evidence supporting the feasibility and benefits of enteral nutrition, especially during the remission-induction treatment phase. Chapter 2.3 indicates that adherence to the nutritional guidelines may be enhanced by improved nutrition education for HCPs, better dissemination of and continuous access to nutritional guidelines, enhanced interprofessional collaboration, and stronger scientific evidence of guideline recommendations.\n\nIn addition, Chapter 2.2 explores the experiences and perspectives of AML patients regarding nutrition-related problems during intensive treatment, the nutritional care they received, MNT, and the variations in nutritional support practices among hospitals. For many of these patients, nutritional problems and related physical decline were major sources of distress. They considered nutritional support, including MNT, as crucial for countering malnutrition and minimizing physical decline. Moreover, MNT often provided peace of mind and was even perceived as a lifeline. Inconsistencies in nutritional support practices among hospitals, however, contributed to emotional distress, raised concerns, and reduced confidence in health care. Patients also expressed a preference for parenteral over enteral nutrition, primarily due to concerns about the enteral tube placement and tube-related discomfort.\n\nThe ESPEN\/EBMT guidelines emphasize that nutritional interventions, such as MNT, should primarily aim at preserving or increasing FFM\/muscle mass, as its loss is the key aspect of cancer-related malnutrition that is associated with its adverse outcomes, including physical impairment, complications, treatment-related toxicity, and mortality (5, 6, 20, 22, 23). Additionally, preserving fat mass (FM) may also be relevant, as previous studies suggest that low FM may be a significant negative prognostic factor for survival in AML patients (24, 25).\n\nDespite the evidence showing that preserving FFM\/muscle mass and\/or FM is associated with better outcomes in AML, it has been debated whether nutritional therapy is truly effective in maintaining FFM\/muscle mass and FM (7, 24-27). The primary uncertainty lies in whether malnutrition itself serves as a prognostic risk factor or merely reflects disease severity, suggesting that it may be unmodifiable through nutritional interventions (7, 22, 26, 28). To obtain evidence on the impact of MNT on body composition and outcomes in AML\/MDS patients, ideally, randomized controlled trials (RCTs) comparing MNT with no MNT should be conducted (7). However, such studies are scarce (29, 30), primarily due to ethical concerns about withholding MNT from patients with inadequate intake (7, 28). A single RCT from 1987 demonstrated that prophylactic parenteral nutrition was more effective than hydration alone in preserving body weight, and was associated with improved survival (29). However, given the advancements in treatment protocols since then (3), the relevance of these findings to current practice remains uncertain. Additionally, body composition was not assessed in this study, limiting understanding of the effects of MNT beyond maintaining body weight (29). Moreover, this study, like most nutritional studies in AML\/MDS patients, primarily focused on the HSCT phase (7, 31-36), while data on the remission-induction treatment phase are lacking. The only study that assessed body composition changes in AML patients during remission-induction therapy reported a significant loss of FFM\/muscle mass, while FM was preserved; however, it lacked data on the strategy toward MNT (37).\n\nTo address the gaps in knowledge, the second aim of this thesis, outlined in Chapter 3, was to explore the associations of proactive versus wait-and-see approaches toward MNT with changes in body composition, as well as physical and clinical outcomes in AML\/MDS patients during intensive remission-induction treatment. It is unique that the studies in Chapter 3 were able to compare these two approaches. This was achievable, because one hospital in the Netherlands followed a wait-and-see approach toward MNT in these patients, limiting its use to exceptional and severe cases only, while other hospitals proactively initiated MNT as soon as nutritional intake became inadequate (5, 20, 21).\n\nChapter 3.1 presents a multicenter prospective observational study that assessed changes in nutritional status, including body composition, in AML\/MDS patients receiving proactive nutritional support and MNT during intensive remission-induction treatment. In addition, this study explored the associations between changes in nutritional status and physical and clinical outcomes. Results showed adequate nutritional intake in 91% of 126 AML\/MDS patients, with 61% receiving MNT. Despite this, body weight and indicators of FFM\/muscle mass declined significantly, while markers of FM remained stable. Furthermore, better maintenance of body weight was significantly associated with shorter fever duration, fewer complications, and a shorter hospital length of stay, better maintenance of waist circumference with shorter fever duration, increases in mid-upper arm muscle circumference with improved physical functioning and a shorter hospital length of stay, and increases in Patient-Generated Subjective Global Assessment scores with more fatigue. No significant associations were found between changes in nutritional status variables and muscle strength or time to neutrophil recovery.\n\nChapter 3.2 compared physical and clinical outcomes between 111 patients who received intensive AML treatment at the hospital with a wait-and-see approach toward MNT, and 102 patients at two other hospitals, where parenteral nutrition was proactively started upon inadequate intake. Results demonstrated that proactive use of parenteral nutrition was associated with better maintenance of body weight compared to the exceptional use of MNT. Additionally, decreasing body weight was associated with a longer hospital length of stay but did not impact survival rates. The short-term use of parenteral nutrition was associated with transient mild to moderate elevations (Common Terminology Criteria for Adverse Events < grade 3-4) in serum liver enzymes, but did not correlate with serum bilirubin levels.\n\nChapter 3.3 examines the associations of proactive versus wait-and-see approaches toward MNT with changes in body composition, and physical and clinical outcomes in AML\/MDS patients undergoing intensive remission-induction treatment. These associations were explored by comparing patients treated in hospitals with a proactive approach toward MNT to those treated in a hospital following a wait-and-see strategy. Additionally, the associations between body composition changes and physical and clinical outcomes were explored, and whether these associations differed between the proactive and wait-and-see approaches toward MNT. In this multicenter prospective correlational study, 140 patients from five hospitals where MNT was used proactively, were compared with 64 patients from a hospital that followed a wait-and-see approach toward MNT. In the proactive MNT approach hospitals, 57% of patients received MNT during the first chemotherapy, compared to only 8% in the wait-and-see hospital (p < 0.0001). Results indicated that the proactive approach toward MNT was associated with fewer nutrition impact symptoms, fewer complications, and a shorter hospital length of stay. A significantly higher proportion of patients achieved adequate energy and protein intake (including both oral intake and supplementation via MNT) with the proactive MNT approach, and the incidence of severe malnutrition was lower. Body weight and FFM\/muscle mass decreased significantly in both groups, but body weight was better maintained with the proactive approach toward MNT compared to the wait-and-see strategy, primarily due to enhanced preservation of FM. Similar results were observed during the second chemotherapy cycle. Better maintenance of body composition parameters was associated with improved physical functioning, shorter fever duration, fewer complications, reduced fatigue, and a shorter hospital length of stay. Several associations differed significantly between the two MNT strategies. The decreased body composition parameters were associated with worse physical and clinical outcomes in the wait-and-see hospital, while in the proactive MNT approach hospitals these associations were opposite or attenuated, and non-significant.\n\nChapter 4 summarizes and discusses the insights that emerged from this thesis, including its methodological considerations, and provides recommendations for improving nutritional support in AML\/MDS patients undergoing intensive treatment. This thesis demonstrates variability in adherence to the current nutritional guidelines, which recommend starting MNT when nutritional intake becomes inadequate and favoring enteral nutrition over parenteral nutrition as the first-choice MNT, unless severe gastrointestinal symptoms occur. This variability in adherence has led to considerable differences among hospitals in the timing of MNT initiation and the type of MNT (enteral or parenteral) used as the first-line option. Since many AML\/MDS patients transfer between hospitals during intensive treatment, they are often confronted with these inconsistencies in the use of MNT, which can lead to confusion, emotional distress and decreased confidence in health care.\n\nIn addition, this thesis presents unique studies, comparing a proactive approach toward MNT (where MNT is initiated immediately when nutritional intake becomes inadequate) with a wait-and-see strategy (where MNT is used in severe and exceptional cases only) in AML\/MDS patients undergoing intensive remission-induction treatment. Based on the findings of this thesis and the existing literature, it can be concluded that a proactive approach toward MNT should be used during intensive remission-induction treatment of AML\/MDS patients. This proactive approach involves consultation by a registered dietitian as an integral component of standard supportive care, and the initiation of MNT when oral intake becomes inadequate (<60-75% of energy and\/or protein requirements), and is expected to remain insufficient for a duration of \u22653 to 7 days. It is recommended that all hospitals in the Netherlands uniformly adopt this proactive approach and further reduce inconsistencies in nutritional support practices across hospitals during intensive AML\/MDS treatment. Previous research has demonstrated that enhancing adherence to nutritional guidelines and incorporating them into clinical care pathways can contribute to more uniformity in nutritional support practices (38-41). Additionally, it can improve the quality of nutritional care and lead to better patient and treatment outcomes, such as shorter hospital stays, fewer complications, reduced readmissions, and increased survival (38-41). To promote proactive nutritional support and proactive use of MNT, and to reduce unwanted variability in clinical practice, Chapter 4 introduces a nutritional support pathway for the management of malnutrition in AML\/MDS patients undergoing intensive treatment, incorporating current nutritional guidelines and the findings of this thesis (Chapter 4, Figure 2, (42)). Adherence to this nutritional support pathway can be facilitated by the following strategies emerging from this thesis, including continuous nutrition education for HCPs, effective dissemination of the support pathway and other relevant nutritional knowledge, interprofessional collaboration, and ongoing nutritional research. As this thesis showed that a proactive approach toward MNT, which resulted in adequate energy and protein intake, could not prevent the loss of FFM\/muscle mass and muscle strength in intensively treated AML\/MDS patients, future studies should explore whether a multimodal approach can mitigate these losses. Such a multimodal approach may include more intensive exercise programs, tailored MNT (e.g., MNT enriched with omega-3 fatty acids, branched-chain amino acids, and hydroxymethylbutyrate), anti-inflammatory and\/or orexigenic drugs (22, 23, 26, 27, 43, 44).","auteur":"Rianne Van Lieshout","auteur_slug":"rianne-van-lieshout","publicatiedatum":"4 juli 2025","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/riannevanlieshout?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604090900","isbn":"978-94-6510-579-6","doi_nummer":"","naam_universiteit":"Universiteit Maastricht","afbeeldingen":12852,"naam_student:":"","binnenwerk":"","universiteit":"Universiteit Maastricht","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10177","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=10177"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10177\/revisions"}],"predecessor-version":[{"id":10178,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/10177\/revisions\/10178"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/12852"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=10177"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=10177"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}