Clinical Significance of Bone Marrow Fibrosis in Patients with Polycythemia Vera

Abstract

Abstract 5149 Background:Polycythemia vera (PV) is a heterogeneous myeloproliferative disease characterized by expansion of morphologically normal red blood cells, granulocytes, and platelets with varying degrees of bone marrow fibrosis (BMF) during the disease course. BMF as a result of abnormal deposition of reticulin and collagen fibers in bone marrow stroma plays a role in the pathophysiology and clinical manifestation of myeloproliferative disorders in general. However, in PV, older age and previous history of thrombosis remain the only two major risk factors for consideration in decisions regarding therapy. Objectives:To investigate the characteristics associated with BMF and its prognostic impact on clinical manifestation, overall survival (OS), and transformation to primary myelofibrosis and acute leukemia in patients with PV. Methods:We conducted a retrospective chart review analysis of 115 patients who were diagnosed with PV according to World Health Organization criteria and were referred to MD Anderson Cancer Center between May 2000 and December 2009. Results of the first bone marrow biopsy done at MD Anderson were reviewed. BMF was documented according to the European consensus grading system (MF0-3), in which MF-3 is the most severe grade of fibrosis. Results:Of the 115 patients, 23 (20%) had MF-0, 46 (40%) MF-1, 36 (31%) MF-2, and 10 (9%) MF-3. Table 1 summarizes patient characteristics and outcomes by grade.Table 1:Patient characteristics and outcomes by gradeNumber of patients (%) or median value (range)P valueMF-0MF-1MF-2MF-3Total number of patients23 (20%)46 (40%)36 (31%)10 (9%)0.505Median age, years61 (23–78)52 (16–80)50.5 (24–83)52 (29–84)0.615Race0.476White19/23 (83%)41/46 (90%)30/36 (83%)10/10 (100%)Hispanic4/23 (17%)2/46 (4%)4/36 (11%)0/10 (0%)Black0/10 (0%)1/46 (2%)2/36 (6%)0/10 (0%)Misc0/10 (0%)2/46 (4%)0/36 (0%)0/10 (0%)Constitutional Symptoms4/23 (17%)10/46 (22%)5/36 (14%)3/10 (30%)0.65Fatigue10/23 (43%)17/46 (37%)12/36 (33%)5/10 (50%)0.74Bleeding1/23 (4%)0/46 (0%)3/36 (8%)4/10 (40%)<0.001Thrombosis7/23 (30%)1/46 (2%)4/36 (11%)2/10 (20%)0.007Median liver size, cm0 (0–0)0 (019–4)0 (0-2)0 (0–0)0.695Median spleen size, cm0 (0–22)0 (019–12)0 (0-12)1.5 (019–21)0.201Performance status0 (0–1)0 (0–2)0 (0–1)0 (019–1)0.901HGB15 (12.1–17.5)14 (8.9-18.3)14.4 (11.818.8)15.4 (12–17.8)0.372WBC10.7 (3.2–16.5)10.9 (3.7–23.1)12.1 (5.6–40.5)13 (7.1–74)0.932PLT374 (61–937)430 (311–883)520 (1319–923)389 (38-937)0.256Abnormal cytogenetics2/23 (9%)5/46 (11%)1/46 (2%)3/10 (30%)0.077(+) JAK2 mutation16/23 (69%)22/46 (48%)18/36 (50%)5/10 (50%)0.362Prior malignancy2/23 (9%)2/46 (4%)3/36 (8%)1/10 (10%)0.838Secondary malignancy2/23 (9%)4/46 (9%)3/36 (8%)1/10 (10%)0.99Median OS, months90.25Not reached129.7579.250.398Median EFS, months8410374740.349Transformation to myelofibrosis0/23(0%)3/46 (6%)2/36 (6%)2/10 (20%)0.111Transformation to acute leukemia0/23(0%)0/46 (0%)1/36 (3%)1/10 (10%)0.179Disease duration, months (from diagnosis to time of biopsy)39.542.7516.2539.80.142 Conclusion:Severe BMF was associated with higher risk of bleeding and thrombosis and larger spleen in patients with PV. There was no association between BMF severity and the demographic or symptoms of the disease. There was no association between BMF severity and the presence of JAK2 mutation or cytogenetic abnormalities. There was no impact of BMF on OS, EFS, or transformation to myelofibrosis or acute leukemia. However, longer follow-up is needed to investigate further the impact of BMF on OS and transformation-free survival. Disclosures:No relevant conflicts of interest to declare.