Abstract

Abstract 3918

Poster Board III-854

BACK GROUND

We have previously demonstrated that the myeloproliferative neoplasms (MPNs) of primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocythemia (ET) can lead to weight loss, splenomegaly and constitutional symptoms (Cancer 2007;109:68–76). Additionally we have demonstrated that hypocholesterolemia in MPN patients is associated with decreased survival (Blood 2007;110:a2548). Given that current JAK2 inhibitor trials are demonstrating the ability to reverse MPN associated splenomegaly (Haematologica 2009;94(Suppl 2)439 a1088) and cachexia (Blood 2008;112(11):a1760) we sought to determine the baseline natural history for these variables in patients treated prior to the JAK2 inhibitor era.

METHODS

We analyzed the Mayo MPN database for patients (not treated with JAK2 inhibitors) 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: Patients

783 patients with MPNs (followed for a median of 51 months (range 1-871 months); 60% having expired) were identified for the analysis (PV=158, ET=255, PMF=370) with 541 (69%) having a weight at the time of diagnosis, the remainder had a weight obtained a median of 7.8 months after diagnosis. Additionally, 508 patients (65%) had a weight value available from 1–3 additional time points during the course of their disease. Corresponding measurements of splenomegaly, or absence thereof, were noted in 766 cases (98%). Lipid panels (obtained within 18 months of diagnosis) were available in 264 patients. Results by MPN disease type are listed in the Table.

Table

Serial changes in weight, splenomegaly and cholesterol in 783 MPN Patients

 PV(N=158) ET(N=255) PMF(N=370) P = 
Weight     
-BMI (Dx) (median:range) 25.1 (18-40) 26.0 (17.1-56) 25.4 (17.7-55.1) 0.77 
-BMI Category Decrease over time? 21% 18% 16% 0.36 
->10% Weight Decrease over time? 26% 20% 22% 0.44 
->20% Weight Decrease over time? 8% 8% 5% 0.31 
-% Overweight (BMI >25) at diagnosis 51% 59% 54% 0.46 
-% Underweight (BMI<18.5) at diagnosis 2% 3% 2% 0.38 
Splenomegaly     
-% With Palpable spleen at Diagnosis 33% 15% 81% <0.001 
-% With Spleen Increase over Time? 62% 60% 38% <0.001 
-% > 5cm BLCM Ever 30% 26% 80% <0.001 
-% >10cm BLCM Ever 17% 5% 39% <0.001 
Lipids     
-Cholesterol (Total) mg/dL (median:range) 164 (98-412) 202 (89-342) 153 (12-291) <0.001 
-% with Cholesterol (T) <150 mg/dL 24% 12% 47% <0.001 
-HDL mg/dl (median:range) 42 (23-56) 49 (22-90) 33 (8-133) <0.001 
-% with HDL <60 mg/dL 100% 73% 92% <0.001 
 PV(N=158) ET(N=255) PMF(N=370) P = 
Weight     
-BMI (Dx) (median:range) 25.1 (18-40) 26.0 (17.1-56) 25.4 (17.7-55.1) 0.77 
-BMI Category Decrease over time? 21% 18% 16% 0.36 
->10% Weight Decrease over time? 26% 20% 22% 0.44 
->20% Weight Decrease over time? 8% 8% 5% 0.31 
-% Overweight (BMI >25) at diagnosis 51% 59% 54% 0.46 
-% Underweight (BMI<18.5) at diagnosis 2% 3% 2% 0.38 
Splenomegaly     
-% With Palpable spleen at Diagnosis 33% 15% 81% <0.001 
-% With Spleen Increase over Time? 62% 60% 38% <0.001 
-% > 5cm BLCM Ever 30% 26% 80% <0.001 
-% >10cm BLCM Ever 17% 5% 39% <0.001 
Lipids     
-Cholesterol (Total) mg/dL (median:range) 164 (98-412) 202 (89-342) 153 (12-291) <0.001 
-% with Cholesterol (T) <150 mg/dL 24% 12% 47% <0.001 
-HDL mg/dl (median:range) 42 (23-56) 49 (22-90) 33 (8-133) <0.001 
-% with HDL <60 mg/dL 100% 73% 92% <0.001 

BLCM: Below left costal margin

Impact on prognosis

Univariate analysis of variables discussed which negatively impacted survival included the subtype of MPN (not surprisingly worse for PMF p<0.001), weight loss of greater than 10% during the course of follow-up (P<0.001), or development of splenomegaly of >10 cm below the left costal margin (p=0.004) whereas hypocholesterolemia was significant only for the subset of PMF patients (P=0.03). The IWG-MRT International Prognostic Score (IPSS - Cervantes et. al. Blood 2009) was the only variable prognostically relevant in multivariate analysis (P<0.001).

Conclusions

Progressive splenomegaly, weight loss, and hypocholesterolemia are common across all MPNs but are most prognostically detrimental in PMF. Ongoing and future trials of JAK2 inhibitors will answer whether reversal of these latter hypercatabolic and proliferative manifestations of disease will improve outcomes for MPN patients.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.