Patient-Reported Fatigue, Functional Aspects and Quality of Life in Elderly Patients with High-Risk Myelodysplastic Syndromes. Evidence From a Large Prospective International Study.
Authors: Efficace Fabio , Gaidano Gianluca , Voso Maria Teresa , Caocci Giovanni , Breccia Massimo , Stauder Reinhard , Selleslag Dominik , Sanpaolo Grazia , Platzbecker Uwe , Criscuolo Marianna , Tucci Anna Di , Lunghi Monica , Jonasova Anna , Buccisano Francesco , Ricco Alessandra , Huiyong Zhang , Bowen David , Palumbo Giuseppe A , Niscola Pasquale , Cottone Francesco , Vignetti Marco , Mandelli Franco 
Published: October 2019

Abstract
Abstract 3163

Background:
Fatigue can potentially compromise activities of daily living and functional abilities in patients with myelodysplastic syndromes (MDS). These patients typically also have a limited life expectancy, thus making the improvement of health-related quality of life an important goal of therapy. However, there is paucity of evidence-based data in this area.

Aims:
To investigate the relationships between fatigue and physical, social and emotional functions in high-risk MDS patients and to evaluate socio-demographic and clinical characteristics associated with fatigue.

Methods:
Newly diagnosed patients with intermediate-2 or high-risk IPSS score are recruited in an international prospective observational study. Current analysis is based on patients recruited in 37 centers. A number of socio-demographic, clinical and laboratory variables were collected prior to treatment. Also, fatigue and functional abilities were measured before treatment start. Fatigue was evaluated with the FACIT-Fatigue scale. This is a simple 13-item psychometrically robust questionnaire that assesses self-reported tiredness, weakness and difficulty conducting usual activities due to fatigue. Functional abilities and quality of life (QoL) were assessed with the EORTC QLQ-C30. Both questionnaires have undergone rigorous linguistic cross-cultural validation and were available for all patients in the appropriate language. Functional aspects investigated included: physical (PF), role (RF), emotional (EF), cognitive (CF) and social functioning (SF). These scales range from 0 to 100, with higher scores representing better outcomes. Based on previous research, 10-points were considered to be a minimally important difference (MID) for the functional and QoL scales investigated. A score difference at least equal to MID was considered as a clinically meaningful difference. The cohort was divided into four groups based on the FACIT-Fatigue scores quartiles and patients were defined as having low, low/medium, medium/high and high fatigue levels. All variables investigated were summarized according to fatigue levels. Associations between fatigue levels and functional aspects, socio-demographic characteristics (i.e., age, gender, living arrangements, education) and clinical data (i.e., performance status and IPSS risk) were investigated using Chi-square and Kruskall-Wallis tests as appropriate. Multivariate stepwise regression analysis was also performed to investigate the impact of self-reported fatigue on functional scales.

Results:
Analysis is based on 240 patients, of whom 77% and 23% respectively classified with intermediate-2 and high-risk IPSS score. Median age of patients was 71 years (36% female and 64% male) and 49% had at least one comorbidity. Seventy-three percent of patients had an ECOG performance status ≥1. Patients with higher levels of fatigue reported worse scores in all functional aspects investigated. PF, RF and SF scales were found to be the most compromised aspects by fatigue severity. Mean score differences, between patients reporting low versus high fatigue levels were not only statistically significant (P<.001), but also clinically meaningful being respectively: 45, 54 and 43 points for the PF, RF and SF scales. Also, higher fatigue was associated with poorer QoL outcomes. Mean scores of patients with low versus high levels of fatigue were respectively: 70 (SD 19,1) and 31.2 (SD, 22.8). Mean score difference, between patients reporting low versus high fatigue levels were also statistically significant (P<.001) and clinically meaningful being of 39 points. Multivariate analyses showed that the association between fatigue and all functional aspects and QoL was independent of age, gender, education, time from diagnosis and transfusion dependency. Investigation of possible determinants of fatigue severity revealed that this was not significantly associated with age, gender, IPSS risk category, WHO classification, comorbidity and living arrangements.

Conclusion:
This study suggests that fatigue is the major factor greatly compromising functional abilities and QoL in high-risk MDS patients before treatment. Successfully treating fatigue is crucial to improve functional abilities in these patients and to maximize treatment outcomes.

Disclosures:
No relevant conflicts of interest to declare.