Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency

• Type of Material: Article
• Authors: Hanny Al-Samkari, Harvard University; Eduard J. van Beers, Universitair Medisch Centrum Utrecht; D. Holmes Morton, Lancaster General Hospital; Stefan W. Eber, Technical University Munich; Satheesh Chonat, Emory University; Kevin H. M. Kuo, University of Toronto; Nina Kollmar, Klinikum Kasse; Heng Wang, DDC Clinic for Special Needs Children; Vicky R. Breakey, McMaster University; Sujit Sheth, Weill Cornell Medical College; Mukta Sharma, University of Missouri Kansas City; Peter W. Forbes, Boston Children’s Hospital; Robert J. Klaassen, University of Ottawa; Rachael F. Grace, Harvard University
• Language: English
• Date: 2022-03-22
• Publisher: American Society of Hematology
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by The American Society of Hematology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2021004675
• Title of Journal or Parent Work: Blood Advances
• Volume: 6
• Issue: 6
• Start Page: 1844
• End Page: 1853
• Grant/Funding Information: The Pyruvate Kinase Deficiency Natural History Study was supported by Agios Pharmaceuticals. H.A.-S. is the recipient of a Harvard KL2/Catalyst Medical Research Investigator Training Award and an American Society of Hematology Scholar Award.
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Human Development

Abstract

Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we used validated measures to assess the impact of disease on HRQoL (EuroQol 5-Dimension Questionnaire, Pediatric Quality of Life Inventory Generic Core Scale version 4.0, and Functional Assessment of Cancer Therapy-Anemia) and fatigue (Patient Reported Outcomes Measurement Information System Fatigue and Pediatric Functional Assessment of Chronic Illness Therapy-Fatigue). Significant variability in HRQoL and fatigue was reported for adults and children, although individual scores were stable over a 2-year interval. Although adults who were regularly transfused reported worse HRQoL and fatigue compared with those who were not (EuroQol-visual analog scale, 58 vs 80; P = .01), this difference was not seen in children. Regularly transfused adults reported lower physical, emotional, and functional well-being and more anemia symptoms. HRQoL and fatigue significantly differed in children by genotype, with the worst scores in those with 2 severe PKLR mutations; this difference was not seen in adults. However, iron chelation was associated with significantly worse HRQoL scores in children and adults. Pulmonary hypertension was also associated with significantly worse HRQoL. Additionally, 59% of adults and 35% of children reported that their jaundice upset them, identifying this as an important symptom for consideration. Although current treatments for PKD are limited to supportive care, new therapies are in clinical trials. Understanding the impact of PKD on HRQoL is important to assess the utility of these treatments.