Background:Elevated Body Mass Index (BMI) is a growing health problem worldwide, leading to enhanced mortality and increased risk of several cancers including the Philadelphia‐chromosome negative myeloproliferative neoplasms (MPN) (Leal, Int J Cancer. 2014). MPN patients often suffer from a severe symptom burden and reduced quality of life (Qol) (Mesa, Cancer. 2007). Furthermore, evidence states that BMI is associated with severity of symptom burden among cancer patients (Fang, Breast Cancer Res Treat. 2013), a finding that has only sparsely been investigated in an MPN context.Aims:To examine whether deviations from a normal BMI in an MPN population are associated with higher symptom burden and reduced QoL.Methods:A combined analysis of data (n = 3114) from two large cross‐sectional surveys, the Danish Population‐based Study, MPNhealthSurvey (n = 2044) and the international Fatigue Study (N = 1070) was done. Symptom burden and quality of life were assessed using the validated MPN‐SAF questionnaire (Scherber, Blood. 2011). BMI was split into underweight (<18.5), normal weight (18.5–24.9), overweight (25.0–29.9) and obese (≥ 30), and analysis of covariance was used to estimate the effects of different BMI categories on symptom scores while adjusting for age, gender and MPN subtype.Results:The two study populations were significantly different; The Fatigue Study had a higher proportion of females (66.0% vs 56.3%, P < 0.0001), the participants were younger (58.8y vs 69.0, P < 0.0001) and a higher percentage were newly diagnosed (5.1 vs 0.6 P < 0.0001). For both studies Normal Weight was most frequent (total 50.3%), followed by Overweight (total 31.6%), then Obese (total 15.8%) and least frequent Underweight (2.3%). Despite differences in baseline characteristics, a U‐shaped association between BMI and Total Symptom Burden (TSS) was observed in both dataset with significant higher mean scores for underweight and obese patients relative to normal weight (Figure 1). Furthermore, the U‐shaped pattern was also found for several of the single symptoms: early satiety (increase: underweight 48.8%/obese 12.4%), inactivity (increase: underweight 32.8% /obese 51.3%), cough (increase: underweight 57.8%/obese 47.8%) and impaired QoL as well (increase: underweight 26.6%/ obese 17.9%). Finally, our data showed that obese patients had significant higher mean scores (range 12.4–52.7%) compared to patients with normal BMI for nearly the entire spectrum of MPN‐SAF symptoms (difference in mean: fatigue = 0.95 P < .001, early satiety = 0.32 P = .02, abdominal pain = 0.46 P < .001, abdominal discomfort = 0.46 P < .001, inactivity = 1.22 P < .001, headache = 0.40 P = .002, concentration problems = 0.71 P < .00, dizziness = 0.52 P < .001, numbness = 0.90 P < .001, insomnia = 0.77 P < .001, sad mood = 0.64 P < .001, sexuality problems = 0.89 P < .001, cough = 0.77 P < .001, night sweats = 0.81 P < .001, itching = 0.86 P < .001, bone pain = 0.97 P < .001, QoL = 0.52 P < .001, and TTS = 5.70 P < .001) with fever and weight loss as the only exceptions.Summary/Conclusion:In two large cross‐sectional studies, a U‐shaped relationship between BMI and total symptom burden, several single symptoms and not least QoL was found; A pattern that was consistent both in the combined and separate analysis, remaining significant after adjusting for age, gender and MPN‐subtype. Bearing in mind, that other confounders may be present this is a critical finding as BMI is a modifiable factor in the care of MPN patients with the potential of safe interventions to contribute to reduced symptom burden and improved QoL among MPN patients.image