Universität zu Köln

Althoff, Kathrin Carola (2024). Analysis of immunometabolic and nutritional scoring systems and the body-mass-index as prognostic markers for treatment outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation. PhD thesis, Universität zu Köln.

PDF aktuelleMASTERDissertation_31_07_24_KCA.pdf - Updated Version Download (3MB)

Abstract

Introduction: This study examines the potential impact of metaflammation on the outcomes of allogeneic stem cell transplantation by using the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) to assess the risk of therapy-associated morbidity and mortality. Obesity is considered a significant risk factor, quantified according to the Body Mass Index (BMI) introduced by the World Health Organization (WHO). Chronic systemic inflammation is considered a molecular biological pathomechanism associated with obesity; interactions between hypertrophied adipose tissue and the immune system are summarized with the term "metaflammation." This study was conducted under the hypothesis that recipient-related metaflammation could influence the outcome of allogeneic stem cell transplantation. Project description: Clinical data and routinely acquired laboratory data were analyzed from patients undergoing allogeneic stem cell transplantation at the department for internal medicine (“Klinik I für Innere Medizin”) at University Hospital Cologne between 2012 and 2017. In addition to BMI, metabolic and immunological laboratory parameters were collected. The primary endpoints of the analyses were overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and the incidence as well as severity of acute graft-versus host-disease (aGvHD/GvHD-I). Materials and methods: Laboratory- and transplantation-specific data as well as general patient data were collected before beginning of conditioning therapy and up to day 100 post transplantation. The analysis of the total cohort and a homogeneous subgroup was performed based on gender characteristics and BMI. The subgroup was characterized by the following features: conditioning therapy performed with reduced intensity, matched-related donor/matched unrelated donor and 10/10 HLA and peripheral stem cell source. Results: A total of 461 patient cases were included in the analyses. A subgroup consisting of 251 patients was formed. In the gender-specific analysis, the group of overweight male patients (BMI 25-29.9) had the best survival rate at 62% after 69 months (p-value 0.0082** log-rank test). The female total cohort showed a survival advantage in the group with BMI ≥25 and also in BMI >30. Patients with BMI >30 had the highest incidence of aGvHD and there was an association with high non-relapse-mortality (NRM). Evaluations of nutritional status based on systemic inflammatory response using the Glasgow Prognostic Score showed the following 8 results in the total cohort immediately after engrafting on day 30: hypoalbuminemia corresponding with malnutrition and simultaneous systemic inflammation reaction showed the lowest survival rate at 15% after 57 months (GPS 2) compared to 48% in GPS 0 and 44% in GPS 1, each measured after 60 months (p-value <0.0001*** log-rank test); Patients with GPS 2 also showed the highest NRM with 71% deceased patients after 57 months compared to an NRM rate of 23% in GPS 0 and 35% in GPS 1 after 60 months. Conclusion: Gender-specific differences were observed in overall survival: a BMI >25 and also >30 appeared to have a survival advantage for female patients. In contrast, male transplant recipients only showed a survival advantage in the BMI group >25-30. A BMI >30 had a negative influence on survival in the male cohort. Nutritional status also had a major impact in our analyses, as overweight and malnutrition were investigated independently. However, overweight can appear with malnutrition and also with chronic inflammatory reaction: Malnutrition combined with high NLR and inflammation seems to present a significant negative prognostic factor. Thus, gender-specific investigations and nutritional status along with meta-inflammatory components influence the outcomes of alloHSCT. This study is limited by retrospectively collected data and a small cohort. Besides already established risk assessment scores, it may be possible to develop additional valid scores assessing the nutritional status of the transplant patient and including conditions such as sarcopenia or malnutrition. In the context of allogeneic stem cell transplantation, further prospective cohort studies with larger patient numbers are necessary to validate the scores developed and analyzed in this thesis. The clinical application of scores related to other oncological diseases is also conceivable and should be investigated interdisciplinary in oncological studies.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Althoff, Kathrin Carola k-althoff@gmx.de UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-732451
Date:	2024
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Innere Medizin > Klinik I für Innere Medizin - Hämatologie und Onkologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Nutritional scoring system; BMI; Allogeneic stem cell transplantation; GPS; treatment outcomes English
Date of oral exam:	1 February 2024
Referee:	Name Academic Title Theurich, Sebastian Prof. Dr. med. Schubert, Markus PD Dr. med.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/73245