title: Prognostic value of self-reported fatigue on overall survival in patients with myelodysplastic syndromes: a multicentre, prospective, observational, cohort study.
abstract: BACKGROUND
  The clinical presentation of myelodysplastic syndromes is highly variable and so accurate prediction of outcomes in these patients is crucial. We aimed to assess whether self-reported fatigue severity predicts overall survival beyond gold-standard prognostic indices in patients with higher-risk myelodysplastic syndromes.
  
  
  METHODS
  We did a multicentre, prospective, observational, cohort study of patients from 37 centres in Europe, USA, and east Asia. Adults (≥18 years) with myelodysplastic syndromes were consecutively enrolled within 6 months of diagnosis with an intermediate-2-risk or high-risk score according to the International Prognostic Scoring System (IPSS). Patients were enrolled irrespective of older age, comorbidities, performance status, and progression from a lower IPSS risk score category. All patients had to complete a quality of life assessment at baseline. With use of univariate and then multivariate Cox proportional hazards regression analysis, we constructed a multivariate model of how prognostic variables, including IPSS and fatigue score from the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-core 30, predicted overall survival. The primary endpoint was overall survival by baseline self-reported fatigue scale ratings. This study was registered with ClinicalTrials.gov, number NCT00809575.
  
  
  RESULTS
  Between Nov 10, 2008, and Aug 13, 2012, we enrolled 280 patients with a median age of 71 years (IQR 64-77). The median follow-up was 15 months (IQR 8-27), and the last patient was assessed Feb 16, 2015. The median overall survival from diagnosis was 17 months (95% CI 15-19). In univariate analysis, the baseline factors that were significantly associated with reduced overall survival were increasing age, transfusion dependency (defined as having received at least one red blood cell transfusion every 8 weeks over a period of 4 months), Eastern Cooperative Oncology Group (ECOG) performance status of two or more, increased white blood cell count, high-risk IPSS score, and higher self-reported fatigue severity. In multivariate analysis, baseline factors independently associated with reduced overall survival were high-risk IPSS score (hazard ratio [HR] 2·525, 95% CI 1·357-4·697; p=0·0035) and a higher score for fatigue (1·110, 1·040-1·170, for every ten points of fatigue deterioration; p=0·0007). In further multivariate models for survival, including either the WHO-based prognostic scoring system or the revised version of the IPSS classification, fatigue remained a statistically significant independent prognostic factor with a HR of 1·120 (1·050-1·180, p=0.0003) and a HR of 1·130 (1·060-1·190, p=0·0002), respectively.
  
  
  CONCLUSIONS
  In patients with newly diagnosed higher-risk myelodysplastic syndromes, self-reported fatigue severity provides prognostic information for survival independent from gold-standard risk classifications. Our findings suggest that fatigue assessment should be included in routine diagnostic investigation for these patients and considered as a standard baseline stratification factor in future randomised controlled trials.
  
  
  BACKGROUND
  Associazione Italiana contro le Leucemie, Linfomi e Mieloma (AIL).
authors.affiliation: Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy. Electronic address: f.efficace@gimema.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Efficace
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.affiliation: Department of Hematology, University of Rome Cattolica S. Cuore, Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.affiliation: Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cottone
authors.affiliation: Ematologia e Centro Trapianti, Ospedale Oncologico di Riferimento Regionale Armando Businco, Cagliari, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Angelucci
authors.affiliation: Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caocci
authors.affiliation: Department of Internal Medicine V (Hematology and Oncology), Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Stauder
authors.affiliation: Department of Hematology, AZ St Jan Brugge-Oostende, Belgium.
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.affiliation: Academic Medical Center/University of Amsterdam, Department of Medical Psychology, Amsterdam, Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Sprangers
authors.affiliation: Department of Medicine I, University Hospital Dresden Carl Gustav Carus, Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Department of Emergency and Organ Transplantation, Hematology Section, University of Bari, Bari, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ricco
authors.affiliation: Department of Hematology and Stem Cell Transplantation Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Sanpaolo
authors.affiliation: Department of Internal Medicine, CHU Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Beyne-Rauzy
authors.affiliation: Hematology, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Buccisano
authors.affiliation: UO Ematologia, AOU Policlinico-V Emanuele Catania, Italy.
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Palumbo
authors.affiliation: St James's Institute of Oncology, Bexley Wing, Leeds, UK.
authors.forename: David
authors.initials: D
authors.lastname: Bowen
authors.affiliation: Leukemia Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Khanh
authors.initials: K
authors.lastname: Nguyen
authors.affiliation: Hematology Unit, S Eugenio Hospital, Rome, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Niscola
authors.affiliation: Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Vignetti
authors.affiliation: Italian Group for Adult Hematologic Diseases (GIMEMA), Data Center and Health Outcomes Research Unit, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D015331:Cohort Studies; D005221:Fatigue / Q000175:diagnosis / Q000209:etiology; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D057566:Self Report