The Impact of Medical Comorbidities in MPN-Related Fatigue
Authors: Scherber Robyn M , Senyak Zhenya , Dueck Amylou Constance , Clark Matthew , Boxer Michael , McCallister Archie , Cotter Mary , VanHusen Barbara , Harrison Claire N. , Mesa Ruben 
Published: October 2019

Abstract
Background:
Philadelphia chromosome negative myeloproliferative neoplasms (MPN) include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). Pertinent to these disorders is the high persistence, prevalence, and severity of fatigue. Overall, excessive fatigue compared to age and gender matched controls occurs in greater than 95% of MPN patients (Blood. 2011;118(2):401-8). Physiologic etiologies of fatigue in these patients include cytokine dysregulation and impaired hematopoiesis, however to date no one has investigated the impact that cofounding medical illnesses have on MPN fatigue burden.
Methods:
A 70-item internet-based survey was developed by a team of MPN investigators, patient advocates from MPN Forum, and hosted by the Mayo Clinic Survey Research Center. The survey was promoted online via multiple MPN-related webpages including the MPN Forum, MPN Net, MPN Research Foundation, and MPN Voice during late February to March of 2014. Surveyed data included disease demographics such as splenomegaly, thrombosis, hemorrhage transfusions, medications, and phlebotomies. The MPN-SAF (including the MPN 10) was utilized including the 10-item brief fatigue inventory was used to assess disease burden (Blood. 2011 Jul 14;118(2):401-8). Comorbid conditions were assessed, including hypothyroidism, anemias, sleep disturbances, obesity, and heart and lung disorders.
Data:
Demographics. Overall 1788 MPN patients participated in the survey. Of these, 1676 consented to participate and provided additional data (i.e., completed at least 10 questions). Of these, 555 (33%) patients had ET, 651 (39.0%) had PV, and 417 (25.0%) had MF. Among MF patients, 44.1% had primary MF, 29.7% had post-PV MF, and 26.2% had post-ET MF. Respondents were 68% female with a mean age of 59. Overall brief fatigue inventory score had a mean of 4.4 (range 0-10). MPN-10 score average was 28.4 (range 0-83).
Medical Comorbidities. Overall, many patients endorsed having comorbid medical diseases that could contribute to overall fatigue (Table1). Overall 20.2% of patients endorsed having low thyroid function, with 10% indicating they obtained this diagnosis in the last six months. Twenty three percent endorsed having a new sleep disturbance in the last six months. On average, patients tended to have an average to above average BMI (mean =26.3, median = 25.0). However, many patients also experienced a high rate of unintended weight loss (11.8% with >11lb weight loss in the last 6 months). Cytopenias were also frequently encountered, with 14.7% of participants having required previous transfusions. Among these, 46% required transfusions in the last 6 months. Thrombosis (18.3%), hemorrhage (14.7%), and anemia (48.0%) were relatively common. In the last six months, 11.1% of patients required iron supplementation and 2.2% required erythropoietin injections. Many patients also endorsed the use of medications that could contribute to overall fatigue.
Correlations. Items significantly correlated with worsened fatigue score (BFI greater than or equal to four) included female gender (<0.001), age (p=0.0047), lower education level (<0.001) and lower BMI (<0.001). Current use of alcohol and tobacco was also significantly associated with greater burden of fatigue (<0.001 and 0.0025, respectively). Items not significantly associated with fatigue included DIPSS (MF only), IPSET (ET only) or PV risk scoring.
Conclusions
Overall patients with MPN experience an exclusive pattern of disabling fatigue. Many fatigue-related medications and medical comorbidities may contribute to the debilitating fatigue seen among MPN patients, although no specific comorbidities could account for the high prevalence of fatigue. Rates of comorbid disease burden varied widely compared to the general population. For some diseases including diabetes, rates among MPN populations were less than the general population (National Diabetes Statistics Report, 2014), however the rates of other comorbidities, such as hypothyroidism, were higher (J Clin Endocrinol Metab 2002;87:489–99). Similar to our previous studies, females tended to suffer from a higher mean fatigue burden than males (Geyer ASH 2014). Clinical and research-related determination of fatigue should take into account cofounding comorbid medical conditions that can contribute to overall fatigue burden.

Disclosures
Harrison: Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Shire: Speakers Bureau; CTI: Consultancy; YM Bioscience: Consultancy; Gilead: Consultancy; SBio: Consultancy. Mesa:Incyte: Research Funding; Novartis: Consultancy; Gilead: Research Funding; Genentech: Research Funding; Promedior: Research Funding; Ns Pharma: Research Funding; Celgene: Research Funding; Lilly: Research Funding; Cti: Research Funding.