Increased Incidence of Acute Leukemia in Polycythemia Vera Associated with Chlorambucil Therapy

Abstract

In studies to determine the optimal treatment for polycythemia vera, 431 previously untreated patients whose disease met established diagnostic criteria were entered into a prospective, randomized controlled trial between 1967 and 1974. Three treatment regimens were used: phlebotomy alone, chlorambucil supplemented by phlebotomy, or radioactive phosphorus supplemented by phlebotomy. Despite minor differences in age and sex, the three groups were comparable in initial hematocrit, white-cell and platelet counts, and disease-related symptoms. The median duration of follow-up is now more than 6 1/2 years. As of February 15, 1980, there were no statistically significant differences in survival among the groups. However, the risk of acute leukemia in patients given chlorambucil was 2.3 times that in patients given radioactive phosphorus and 13 times that in patients treated with phlebotomy alone. The increased incidence of leukemia during chlorambucil treatment is statistically significant (P less than or equal to 0.002); accordingly, the Polycythemia Vera Study Group has discontinued the use of chlorambucil in the treatment of polycythemia vera.

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

“…In the first controlled study in PV, the PV study group (PVSG) randomized 431 patients, between 1967 and 1974, to treatment with either phlebotomy alone or phlebotomy with either oral chlorambucil or intravenous radioactive phosphorus (P32) [93]. The results significantly favored treatment with phlebotomy alone with a median survival of 12.6 years compared to 10.9 and 9.1 years for treatment with radiophosphorus and chlorambucil, respectively.…”

The epidemiology of polycythaemia rubra vera in England and Wales 1968-1982

“…There is wide variation in the completeness of cancer registration in England and Wales and it is estimated that some regions register only 60% of cancer cases (Balarajan & Scott, 1983). Since the survival in PV is relatively good, a median of 10 years in clinical series (Berk et al, 1981), one would expect some excess of registrations over deaths. However, in PV there is a 3-4 fold difference between the mortality and registration rates.…”

“…Typically it has a long clinical course that is often complicated by thrombosis and may terminate in acute leukaemia (Berk et al, 1981). There has been little epidemiologic study of PV in recent years because of its relative rarity and the lack of routine sources of morbidity and mortality data.…”

A retrospective study on 226 polycythemia vera patients: impact of median hematocrit value on clinical outcomes and survival improvement with anti-thrombotic prophylaxis and non-alkylating drugs

“…Thrombotic complications are the main cause of morbidity and mortality, occurring in more than one third of patients and causing 35-45% of deaths [5,6]. Other possible adverse events are the evolution into secondary myelofibrosis (MF) or acute myeloid leukemia (AML) occurring in 10-15% [4,[6][7][8] and 2-15% [4,[8][9][10][11][12][13][14][15][16] of patients, respectively, depending on treatments and with increased incidence with long-standing disease.…”