Dynamics, and Prognostic Impact, of Weight Loss in Primary Myelofibrosis
Authors: Mesa Ruben A. , Schwager Susan , Huang Jocelin , Hussein Kebede , Pardanani Animesh D. , Tefferi Ayalew 
Published: April 2020

Abstract
BACK GROUND Primary myelofibrosis (PMF) leads to weight loss, splenomegaly and constitutional symptoms (Cancer2007;109:68–76) and hypocholesterolemia associated with decreased survival (Blood2007;110:a2548). Initial trials of JAK2 inhibitors have demonstrated improvements in these (JCO2008;26:a7004), yet little objective data exists regarding the dynamic changes in weight and spleen size during the course of PMF.
METHODS We analyzed the Mayo PMF database for patients with information on disease prognosis, presentation, therapies, height and weight at diagnosis, and outcomes. Additionally, when available, we analyzed additional weights during the clinical course, the body mass index (BMI- (weight/(height*height)), spleen size, and peripheral blood studies including lipids.
Results: 370 patients with PMF were identified with 193 (52%) having a weight at the time of diagnosis, the remainder had a weight obtained a median of 10.0 months (range 1.8–159) after diagnosis. Additionally, 210 patients (57%) had a weight value available from 1–3 additional time points during the course of their disease. At PMF diagnosis patients had a median BMI of 25.3 (range 17.6 to 38.4), with 53% considered overweight (USA Norms (NHANES 2004): 66% and 32.2% are considered overweight or obese). Although weight lost prior to diagnosis unclear, only 2% of patients would be deemed “underweight” at diagnosis. Serial analysis demonstrated 67% experienced a decrease in weight over time, with 23% and 6% experiencing a &gt;10% or 20% decrease, respectively. Overall during the course of illness 65% of patients remained in the same BMI category with 27% dropping to a lower category and 8% gaining in a category (Table 1).
Table 1. Distribution of Body Mass Index and Spleen Size in 370 PMF patients followed serially
DX of PMF Weight 2 Weight 3 Weight 4 Underweight BMI&lt;18.5 2% 1% 2% 2% Normal BMI=18.5–24.9 45% 41% 41% 54% Overweight BMI=25–29.9 33% 42% 41% 35% Obese BMI&gt;30 20% 16% 16% 10% Spleen Size (cm BLCM) (median: range) 5.0 (0–30) 6 (0–33) 7 (0–33) 7.5 (0–28) Time from PMF DX (median(range) months) 0 10.3 (1.8–159) 28.3 (6–191) 57 (15–258)
Major weight increases were rare &lt;1%, and might include buildup of fluid or splenic mass. Indeed spleen sizes generally increased during the course of the illness, with 51% having “massive” splenomegaly (either &gt;10 (45%) or &gt;20 (20%) cm below left costal margin or requiring splenectomy (19%)). Massive splenomegaly was not associated with weight loss or weight gain, suggesting increasing splenic mass came at the expense of alternate tissue mass (muscle and or fat).
Median survival for the entire cohort was 77 months and PMF prognostic scores being valid (Lille PMF score p&lt;0.01; IWG-MRT PMF Score - Submitted separately Cervantes et. al. p&lt;0.01), however BMI number and category was not independently predictive of survival. Additionally, neither percentage of weight loss nor changing BMI category were associated with decreased survival. Although splenomegaly was not independently associated with decreased survival, the need for splenectomy clearly was (p=0.02). Consistent with our prior observation hypocholesterolemia (total &lt;150 (median of 151 (range 12–366) or a HDL cholesterol of &lt;60 (median 77 (range 25–248)) were associated with decreased survival (p&lt;0.01 and =0.05, respectively). Decreasing weight in PMF patients was most highly correlated with decreases in HDL (p=0.03). Hypocholesterolemia was highly associated with splenomegaly (p&lt;0.001 for spleen size &gt;10 cm at any point during disease course).
Conclusions: Weight loss is common in most PMF patients, despite the confounders of edema and increasing splenomegaly which could mask the degree of loss of lean body mass. Although few PMF patients are considered “underweight” by BMI standards, the distribution compared to USA norms suggest a lower weight distribution. Additionally, patients during the course of their illness are most likely to fall from a BMI overweight category to a “normal” category which may underestimate the true degree of catabolism of muscle mass occurring. Although not independently associated with decreased survival, weight loss remains common and a sign of advancing disease in this terminal illness. More precise methodology to estimate true lean muscle mass lost or gained may yield a better understanding of the hypercatabolic state seen in PMF. Efficacious therapy (such as potentially a JAK2 inhibitor) will likely reverse the trend of weight loss in these patients.