Acute Leukemia in Polycythemia Vera
Acute Leukemia in Polycythemia Vera
Abstract & Commentary
William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.
Synopsis: Factors associated with leukemia development in patients with polycythemia vera were examined in a cohort of 1638 patients enrolled in an observational study. Older age, alkylating agent treatment and female gender were demonstrated to be significant risks, hydroxyurea treatment was not. This well conducted analysis provides useful information about the risks of leukemia development in polycythemia vera.
Source: Finazzi G, et al. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood. 2005;105:2664-2670.
The clinical course of polycythemia vera (pv) is characterized by an uncertain risk of development of myeloid metaplasia with myelofibrosis (MMM) or acute myeloid leukemia/myelodysplasia (AML/MDS). The incidence of AML/MDS ranges from 5-15% after ten years of disease with progressive increase thereafter.1-3 In the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) prospective project, which included 1638 patients with PV, AML/MDS was diagnosed in 22 patients after a median of 8.4 years from the diagnosis of PV. By multivariate analysis, older age was confirmed as the main independent risk factor (hazard ration [HR], 4.30; 95% confidence interval [CI], 1.16-15.94; P = .0294). Exposure to P32 and busulfan, but not to hydroxyurea had an independent role in producing an excess risk for progression to AML/MDS, compared to treatment with phlebotomy or interferon.
COMMENTARY
Polycythemia vera occurs infrequently enough, and complications occur late enough that it would be unlikely that prospective clinical trials will ever conclusively address the leukemia risks of the various treatment approaches in a comparative way. Thus, the ECLAP study may well provide the best opportunity to address these questions. This observational data base utilized clinical monitoring in a manner analogous to clinical trial methodology. Investigators were asked to register all patients with new and old diagnoses of PV, regardless of age, therapy or duration of disease. Data regarding clinical outcomes, treatments, and laboratory values were collected annually for 5 years. The median age of the entire cohort was 62.1 years at diagnosis and PV was diagnosed within 5 years of registration on study in 62% of cases, whereas it was diagnosed in 14.4% of patients more than 10 years earlier. At the time of study closure, patients had been followed for a median of 2.8 years. Twenty-one cases of AML and one case of MDS were diagnosed after a median of 2.5 years (range, 0.5-4.1 years) from the registration and 8.4 years (range, 2.2-19.8 years) from the diagnosis of PV.
The multivariate analysis was interesting. Although there was a trend, the absolute duration of PV did not reach a level of statistical significance with regard to leukemia development. However, patient age was a significant factor. Compared with patients younger than 60, those older than 70 were at significantly higher risk (HR, 4.30; 95% CI, 1.16-15.94; P = 0.0205). Further, unlike other reports in which there was no gender difference, this analysis found an increased risk from AML/MDS in female patients, a finding that could not be explained by older age, duration of disease or prior treatment with alkylating agents. Finally, this analysis would seem to lay to rest the concern that hydroxyurea is leukemogenic in this population.
References
1. Berk PD, et al. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med. 1981;304:441-447.
2. Najean Y, et al. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997;90:3370-3377.
3. Weinfield A, et al. Acute leukaemia after hydroxyurea therapy in polycythaemia vera and allied disorders. Eur J Haematol. 1994;52:134-139.
Factors associated with leukemia development in patients with polycythemia vera were examined in a cohort of 1638 patients enrolled in an observational study. Older age, alkylating agent treatment and female gender were demonstrated to be significant risks, hydroxyurea treatment was not.Subscribe Now for Access
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