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 grade

Number of patients (%) or median value (range)P value
MF-0MF-1MF-2MF-3
Total number of patients 23 (20%) 46 (40%) 36 (31%) 10 (9%) 0.505 
Median age, years 61 (23–78) 52 (16–80) 50.5 (24–83) 52 (29–84) 0.615 
Race     0.476 
White 19/23 (83%) 41/46 (90%) 30/36 (83%) 10/10 (100%)  
Hispanic 4/23 (17%) 2/46 (4%) 4/36 (11%) 0/10 (0%)  
Black 0/10 (0%) 1/46 (2%) 2/36 (6%) 0/10 (0%)  
Misc 0/10 (0%) 2/46 (4%) 0/36 (0%) 0/10 (0%)  
Constitutional Symptoms 4/23 (17%) 10/46 (22%) 5/36 (14%) 3/10 (30%) 0.65 
Fatigue 10/23 (43%) 17/46 (37%) 12/36 (33%) 5/10 (50%) 0.74 
Bleeding 1/23 (4%) 0/46 (0%) 3/36 (8%) 4/10 (40%) <0.001 
Thrombosis 7/23 (30%) 1/46 (2%) 4/36 (11%) 2/10 (20%) 0.007 
Median liver size, cm 0 (0–0) 0 (019–4) 0 (0-2) 0 (0–0) 0.695 
Median spleen size, cm 0 (0–22) 0 (019–12) 0 (0-12) 1.5 (019–21) 0.201 
Performance status 0 (0–1) 0 (0–2) 0 (0–1) 0 (019–1) 0.901 
HGB 15 (12.1–17.5) 14 (8.9-18.3) 14.4 (11.818.8) 15.4 (12–17.8) 0.372 
WBC 10.7 (3.2–16.5) 10.9 (3.7–23.1) 12.1 (5.6–40.5) 13 (7.1–74) 0.932 
PLT 374 (61–937) 430 (311–883) 520 (1319–923) 389 (38-937) 0.256 
Abnormal cytogenetics 2/23 (9%) 5/46 (11%) 1/46 (2%) 3/10 (30%) 0.077 
(+) JAK2 mutation 16/23 (69%) 22/46 (48%) 18/36 (50%) 5/10 (50%) 0.362 
Prior malignancy 2/23 (9%) 2/46 (4%) 3/36 (8%) 1/10 (10%) 0.838 
Secondary malignancy 2/23 (9%) 4/46 (9%) 3/36 (8%) 1/10 (10%) 0.99 
Median OS, months 90.25 Not reached 129.75 79.25 0.398 
Median EFS, months 84 103 74 74 0.349 
Transformation to myelofibrosis 0/23(0%) 3/46 (6%) 2/36 (6%) 2/10 (20%) 0.111 
Transformation to acute leukemia 0/23(0%) 0/46 (0%) 1/36 (3%) 1/10 (10%) 0.179 
Disease duration, months (from diagnosis to time of biopsy) 39.5 42.75 16.25 39.8 0.142 
Number of patients (%) or median value (range)P value
MF-0MF-1MF-2MF-3
Total number of patients 23 (20%) 46 (40%) 36 (31%) 10 (9%) 0.505 
Median age, years 61 (23–78) 52 (16–80) 50.5 (24–83) 52 (29–84) 0.615 
Race     0.476 
White 19/23 (83%) 41/46 (90%) 30/36 (83%) 10/10 (100%)  
Hispanic 4/23 (17%) 2/46 (4%) 4/36 (11%) 0/10 (0%)  
Black 0/10 (0%) 1/46 (2%) 2/36 (6%) 0/10 (0%)  
Misc 0/10 (0%) 2/46 (4%) 0/36 (0%) 0/10 (0%)  
Constitutional Symptoms 4/23 (17%) 10/46 (22%) 5/36 (14%) 3/10 (30%) 0.65 
Fatigue 10/23 (43%) 17/46 (37%) 12/36 (33%) 5/10 (50%) 0.74 
Bleeding 1/23 (4%) 0/46 (0%) 3/36 (8%) 4/10 (40%) <0.001 
Thrombosis 7/23 (30%) 1/46 (2%) 4/36 (11%) 2/10 (20%) 0.007 
Median liver size, cm 0 (0–0) 0 (019–4) 0 (0-2) 0 (0–0) 0.695 
Median spleen size, cm 0 (0–22) 0 (019–12) 0 (0-12) 1.5 (019–21) 0.201 
Performance status 0 (0–1) 0 (0–2) 0 (0–1) 0 (019–1) 0.901 
HGB 15 (12.1–17.5) 14 (8.9-18.3) 14.4 (11.818.8) 15.4 (12–17.8) 0.372 
WBC 10.7 (3.2–16.5) 10.9 (3.7–23.1) 12.1 (5.6–40.5) 13 (7.1–74) 0.932 
PLT 374 (61–937) 430 (311–883) 520 (1319–923) 389 (38-937) 0.256 
Abnormal cytogenetics 2/23 (9%) 5/46 (11%) 1/46 (2%) 3/10 (30%) 0.077 
(+) JAK2 mutation 16/23 (69%) 22/46 (48%) 18/36 (50%) 5/10 (50%) 0.362 
Prior malignancy 2/23 (9%) 2/46 (4%) 3/36 (8%) 1/10 (10%) 0.838 
Secondary malignancy 2/23 (9%) 4/46 (9%) 3/36 (8%) 1/10 (10%) 0.99 
Median OS, months 90.25 Not reached 129.75 79.25 0.398 
Median EFS, months 84 103 74 74 0.349 
Transformation to myelofibrosis 0/23(0%) 3/46 (6%) 2/36 (6%) 2/10 (20%) 0.111 
Transformation to acute leukemia 0/23(0%) 0/46 (0%) 1/36 (3%) 1/10 (10%) 0.179 
Disease duration, months (from diagnosis to time of biopsy) 39.5 42.75 16.25 39.8 0.142 
View Large
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.

Topics:
myelofibrosis, polycythemia vera, leukemia, acute, thrombosis, myeloproliferative disease, signs and symptoms, biopsy, bone marrow biopsy, cancer, disease progression

Author notes

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Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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