The most award winning
healthcare information source.
TRUSTED FOR FOUR DECADES.
Prognostic Importance of Leukocytosis in P Vera
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: In a review of the Mayo Clinic experience over 50 years with polycythemia vera, the prognostic factors including leukocytosis were examined in the context of outcomes such as the development of leukemic or fibrotic transformation, thrombosis and overall survival. At the time of diagnosis, advanced age, a history of arterial thrombosis and leukocytosis were independent predictors of inferior survival. Leukocytosis during follow-up was also a predictor of leukemic transformation and venous thrombosis.
Source: Gangat N, et al. Br J Hematol. 2007;138:354-358.
It is now understood that a JAK 2 mutation occurs in up to 90% of cases of polycythemia vera (PV).1, 2 Compared with the general population, survival is shorter for PV patients, primarily as a consequence of leukemic transformation, development of myelofibrosis, or vascular events.3 Established guidelines target hematocrit of 45% or less in male and 42% or less in female patients.4
Recently, it has been observed that leukocyte counts of greater than 15 x 109/L in patients with polycythemia vera is associated with increased risk for myocardial infarction.5 Leukocytosis is also known to heighten both arterial and venous thrombosis risk6 and reduce survival7 in patients with the related myeloproliferative disorder essential thrombocythemia (ET).
In the current report, Gangat and colleagues review the Mayo Clinic experience with polycythemia vera in the context of leukocytosis. The study population included a review of all records of patients with polycythemia vera at the Mayo Clinic between the years 1956 and 2005 for whom sufficient follow-up data was available through November 2006.
There were 459 study patients available with a median of 64 months (range 0 to 562 months). Among this group there were 146 (31.8%) deaths, 54 (11.8%) post-polycythemia vera myelofibrosis (MF) and 34 (7.4%) leukemic transformations (LT) documented. By univariate analysis, overall survival was negatively associated with advanced age, a history of arterial thrombosis (either at diagnosis or during follow-up) or leukocytosis (using a cutoff level of either 10 x 109/L or 15 x 109/L [P = 0.008 and 0.002, respectively]). By multivariate analysis, age greater than 60 years leukocyte count greater than 15 x 109/L and arterial thrombosis at diagnosis retained their significance with regard to negative impact on overall survival. A risk stratification model based on leukocyte count of greater than 15,000 x 109/L and an age greater than 60 years generated three risk categories with a median survival of 272, 152, and 108 months in the absence of both risk factors or presence of either one or both risk factors respectively (P < 0.001; hazard ratio [HR] for high risk group = 5.57, 95% confidence interval [CI]: 3.45-9.02; HR for intermediate group = 2.18, 95% CI: 1.48 to 3.23).
Among several clinical and laboratory parameters evaluated for association with leukemic transformation, including specific drug exposure history, only leukocytosis was identified as an adverse prognostic factor (P = 0.001 for leukocyte count greater than 15 x 109/L and P = 0.006 or leukocyte count greater than 10 x 109/L).
These results are consistent with an evolving literature describing the prognostic importance of leukocytosis in both polycythemia vera and essential thrombocythemia.6, 8-10 It now appears that an elevated white count in the context of myeloproliferative disorder portends a greater risk for leukemic transformation, venous thrombosis, possibly arterial thrombotic events and less favorable survival. Thus, it becomes a relevant question whether early and aggressive cytoreductive therapy in PV or ET patients with leukocytosis would favorably influence the adverse prognosis associated with the elevated white count.
1. James C, et al. Nature. 2005;434(7037):1144-1148.
2. Scott LM, et al. N Engl J Med. 2007;356(5):459-468.
3. Passamonti F, et al. Am J Med. 2004;117(10):755-761.
4. Barbui T, Finazzi G. Best Pract Res Clin Haematol. 2006;19(3):483-493.
5. Landolfi R, et al. Blood. 2007;109(6):2446-2452.
6. Tefferi A, et al. Blood. 2007;109(9):4105.
7. Wolanskyj AP, et al. Mayo Clin Proc. 2006;81(2):159-166.
8. Carobbio A, et al. Blood. 2007;109(6):2310-2313.
9. Gangat N, et al. Leukemia. 2007;21(2):270-276.
10. Kiladjian JJ, et al. Hematol J. 2003;4(3):198-207.