Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study

Abstract

Under the auspices of an International Working Group, seven centers submitted diagnostic and follow-up information on 1545 patients with World Health Organization-defined polycythemia vera (PV). At diagnosis, median age was 61 years (51% females); thrombocytosis and venous thrombosis were more frequent in women and arterial thrombosis and abnormal karyotype in men. Considering patients from the center with the most mature follow-up information (n=337 with 44% of patients followed to death), median survival (14.1 years) was significantly worse than that of the age- and sex-matched US population (P<0.001). In multivariable analysis, survival for the entire study cohort (n=1545) was adversely affected by older age, leukocytosis, venous thrombosis and abnormal karyotype; a prognostic model that included the first three parameters delineated risk groups with median survivals of 10.9-27.8 years (hazard ratio (HR), 10.7; 95% confidence interval (CI): 7.7-15.0). Pruritus was identified as a favorable risk factor for survival. Cumulative hazard of leukemic transformation, with death as a competing risk, was 2.3% at 10 years and 5.5% at 15 years; risk factors included older age, abnormal karyotype and leukocytes ≥15 × 10(9)/l. Leukemic transformation was associated with treatment exposure to pipobroman or P32/chlorambucil. We found no association between leukemic transformation and hydroxyurea or busulfan use.

Figure 1

Survival in 1545 patients with PV (23% followed to death; median survival 18.9 years) compared with expected survival based on individuals of the same age and gender from the US total population.

Figure 2

Survival in 337 Mayo Clinic patients with PV (44% followed to death; median survival 14.1 years) compared with expected survival based on individuals of the same age and gender from the US total population.

Figure 3

Risk-stratified survival in 1545 patients with PV. Adverse points are assigned to age ⩾67 years (5 points), age 57–66 years (2 points), leukocyte count ⩾15 × 10⁹/l (1 point) and venous thrombosis (1 point): low-risk (0 points), intermediate-risk (1 or 2 points) and high-risk (⩾3 points).

Figure 4

Cumulative incidence of leukemic transformation (LT) in 1545 patients with PV (thin black line), accounting for death as a competing risk (thick black line=cumulative incidence of death). The red line is the cumulative probability of LT ignoring death because of other causes.

Figure 5

Cumulative incidence and time to event for leukemic transformation of PV among 1545 patients stratified by the first cytoreductive drugs they were exposed to. ‘Leukemogenic' drugs include chlorambucil, P32 and other alkylating agents; ‘Non-leukemogenic', for the purposes of Figure 5, signifies the use of interferon α or anagrelide, only; ‘Nothing' refers to patients who were not exposed to any cytoreductive agent.