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Essential thrombocythemia (ET) is a chronic, clinically heterogeneous myeloproliferative neoplasm characterized by an elevated platelet count (≥450 × 109/L) with a favorable prognosis compared with polycythemia vera and primary myelofibrosis. However, 22% of patients with low-risk ET present with extreme thrombocytosis (ExT; platelet count ≥1,000 × 109/L), with an assumed risk for more thrombotic complications. In addition, despite reported data for patients with low-risk ET and ExT suggesting similar rates of subsequent thrombotic events in the presence or absence of prophylactic cytoreductive therapy (24% vs 13%, respectively),1 there remains a lack of evidence to support the optimal treatment of ExT in patients with otherwise low-risk ET.
Tefferi and colleagues recently published a retrospective analysis on vascular events and treatment strategies in patients with low-risk ET and ExT in the American Journal of Hematology, comparing thrombotic events in patients with and without ExT and the impact of cytoreductive and antiplatelet therapy on such events.2
The MPN Hub has previously published a summary of the updates on the diagnosis, risk stratification, and management of polycythemia vera and ET, which can be found here.
Table 1. Baseline characteristics for patients with and without ExT*
Baseline characteristic |
Patients with ExT |
Patients without ExT |
p value† |
---|---|---|---|
Median age, years (range) |
40.1 (17.6–59.2) |
46.5 (18.2–59.5) |
<0.01 |
Female, n (%) |
128 (70.0) |
169 (67.6) |
0.6 |
Median hemoglobin, g/dL (range) |
13.5 (8.4–17.5) |
13.8 (8.5–17.7) |
0.03 |
Hemoglobin <10 g/dL, n (%) |
3 (1.8) |
3 (1.3) |
0.6 |
Median leucocyte count, × 109/L (range) |
9 (3.5–28.1) |
7.9 (3.5–39.0) |
<0.01 |
Leucocyte count ≥11 × 109/L, n (%) |
39/161 (24.2) |
37/242 (15.3) |
0.03 |
CV risk factor, n (%) |
44/137 (32.1) |
89/212 (41.9) |
0.06 |
Palpable splenomegaly, n (%) |
42/179 (23.5) |
45/248 (18.2) |
0.18 |
Driver mutation status, n (%)‡ |
|
|
<0.01 |
Median follow-up, years (range) |
16.1 (1.2–46.9) |
13.2 (1.3–40.6) |
0.01 |
CV, cardiovascular; ExT, extreme thrombocytosis. |
Table 2. Thrombotic events and disease transformation in patients with and without ExT*
Event/classification, n (%) |
Patients with ExT |
Patients without ExT |
p value† |
---|---|---|---|
Major thrombosis after diagnosis |
33/183 (18) |
48/250 (19) |
0.76 |
Major hemorrhage‖ before or after diagnosis |
21/145 (15) |
21/218 (10) |
0.16 |
Microvascular symptoms |
28/145 (19) |
53/215 (25) |
0.23 |
IPSET risk group |
|
|
|
Fibrotic transformation |
41/183 (22) |
39/250 (16) |
0.07 |
Leukemic transformation |
11/183 (6) |
10/250 (4) |
0.34 |
Death |
65/183 (36) |
53/250 (21) |
<0.01 |
ExT, extreme thrombocytosis; IPSET, International Prognostic Score of Thrombosis for Essential Thrombocythemia. |
TFS was significantly better in the presence of aspirin therapy (p = 0.03) among low-risk patients with ExT. A total of 12 events were reported in 78 patients with ExT on initial aspirin therapy compared with 12 events in 35 patients who were not on initial aspirin therapy. Age and aspirin therapy were significant in a multivariate analysis investigating the impact of different variables on TFS (p = 0.02 and p = 0.03, respectively).
Using or not using cytoreductive therapy did not show any difference in TFS among 129 low-risk patients with ExT (p = 0.9). In addition, 8/38 patients on initial cytoreductive therapy developed thrombotic events compared with 18/91 patients who did not receive it.
The data on specific therapy are documented in Table 3, which compared patients with or without ExT depending on treatment modality. As can be seen, the rate of thrombotic events was higher in patients with ExT who received initial cytoreductive therapy compared with patients without ExT, while the reverse was true for initial aspirin therapy. In addition, among patients who experienced arterial events, 61% had received cytoreductive therapy and 33% had received aspirin. In patients who experienced venous events, 39% had received cytoreductive therapy and 34% had received aspirin.
Table 3. The effect of specific therapies on thrombotic events in patients with and without ExT*
Initial treatment |
Thrombotic event, n (%) |
p value† |
|
---|---|---|---|
Patients with ExT |
Patients without ExT |
||
None |
13/137 (10) |
27/209 (13) |
0.32 |
Aspirin alone |
21/101 (21) |
96/191 (50) |
<0.01 |
Aspirin with cytoreductive agent |
45/101 (45) |
48/191 (25) |
<0.01 |
Cytoreductive agents |
91/129 (71) |
79/202 (39) |
<0.01 |
Hydroxyurea |
60/129 (47) |
39/202 (19) |
<0.01 |
Anagrelide |
29/129 (23) |
37/202 (18) |
0.36 |
Interferon |
2/129 (2) |
0 (0) |
0.05 |
ExT; extreme thrombocytosis. |
This retrospective analysis suggests that patients with low-risk ET and ExT are not at a significantly increased risk of thrombotic events compared with patients with ET but without ExT. Furthermore, the analysis showed that there is an association between ExT and a younger age, higher leukocyte count, CALR driver mutations, and shortened overall survival. Interestingly, patients with ExT who develop thrombosis tend to be classified in the low IPSET-thrombosis risk group.
When analyzing the treatment modalities for thrombosis prevention, fewer patients with ExT on initial aspirin therapy developed thrombotic events compared with patients with ExT on cytoreductive drugs. This analysis challenges the benefit of using cytoreductive therapy in reducing thrombotic risk in patients with low-risk ET and ExT and suggests that aspirin therapy should be considered first as prevention for thrombotic events. However, the findings from this retrospective study should be interpreted with caution and further prospective controlled studies are needed to evaluate the benefit of antiplatelet therapy in improving TFS for patients with low-risk ET and ExT.
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