title: Second malignancies in patients with essential thrombocythaemia treated with busulphan and hydroxyurea: long-term follow-up of a randomized clinical trial.
abstract: We have previously demonstrated that hydroxyurea (HU) reduces the rate of vascular complications in patients with essential thrombocythaemia (ET) at high risk of thrombosis. However, the relatively short follow-up (median 27 months) did not enable the evaluation of the risk of developing secondary malignancies. In this study, we report the long-term outcome of the 114 patients included in the trial: 56 patients randomized to receive HU and 58 patients to receive no cytoreductive therapy. Before randomization, 15 patients had been treated with busulphan. During the observation period, 29 patients (50%) shifted from the control to the HU group mainly because of thrombosis. Median follow-up was 73 months (range 3-94). Analysis was by intention to treat and, when indicated, by treatment. When analysed by intention to treat, 46 out of 54 patients (85%) originally randomized in the HU group are alive, compared with 49 of 58 patients (84%) in the control group [not significant (n.s.)]. Five patients (9%) in the HU group and 26 patients (45%) in the control group had thrombosis (P < 0.0001). Seven patients (13%) in the HU group developed secondary acute leukaemia, myelodysplastic syndromes or solid tumours, compared with only one of the control group patients (1.7%) (P = 0.032). The occurrence of secondary malignancies was also analysed by treatment: none of the 20 patients who had never been treated with chemotherapy developed neoplasia vs. three of the 77 patients given HU only (3.9% n.s.) and five of the 15 patients given busulphan plus HU (33% P < 0. 0001). This study showed that: (a) HU reduced the risk of thrombosis in ET patients; (b) the sequential use of busulphan and HU significantly increased the risk of second malignancies; and (c) overall survival was not affected by HU therapy.
authors.affiliation: Divisions of Haematology, Ospedali Riuniti, Bergamo, and Ospedale S. Bortolo, Vicenza, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Finazzi
authors.forename: M
authors.initials: M
authors.lastname: Ruggeri
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: T
authors.initials: T
authors.lastname: Barbui
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D007938:Leukemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced; D016609:Neoplasms, Second Primary / Q000139:chemically induced*; D013920:Thrombocythemia, Essential / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D002066:Busulfan; D006918:Hydroxyurea