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

• Published in: Blood advances Vol. 6; no. 6; pp. 1844 - 1853
• Main Authors: Al-Samkari, Hanny, van Beers, Eduard J., Morton, D. Holmes, Eber, Stefan W., Chonat, Satheesh, Kuo, Kevin H.M., Kollmar, Nina, Wang, Heng, Breakey, Vicky R., Sheth, Sujit, Sharma, Mukta, Forbes, Peter W., Klaassen, Robert J., Grace, Rachael F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.03.2022; American Society of Hematology
• Subjects: Red Cells, Iron, and Erythropoiesis
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2021004675

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. This trial was registered at www.clinicaltrials.gov as #NCT02053480. •The impact of PKD on HRQoL and fatigue is described in 254 children and adults using 6 validated instruments.•Severe anemia, regular transfusion, iron chelation, and nonmissense mutations are associated with worse patient-reported outcomes. [Display omitted]