Acute myeloid leukemia (AML) having evolved from essential thrombocythemia (ET): distinctive chromosome abnormalities in patients treated with pipobroman or hydroxyurea

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Abstract
ET is a chronic myeloproliferative disorder rarely evolving into AML, sometimes preceded by a myelodysplastic syndrome (MDS). Such transformations mostly occur in patients treated with radiophosphorous ((32)P) or alkylating agents, especially busulfan. Recently, concern has also arisen about the long-term safety of hydroxyurea (HU). Pipobroman (PI), a well tolerated and simple to use drug, constitutes a valid alternative to those cytoreductive treatments. The present study reports on 155 ET patients treated at our institution from 1985 to 1995, and monitored until December 2000. A good control of thrombocytosis was achieved with PI as the only treatment in 106 patients and with HU in 23 patients. Twenty-six patients received no treatment. After a median follow-up of 104 months, seven patients (four treated with HU, and three with PI) developed AML whereas one patient treated with PI developed MDS. A significant difference in progression-free survival was observed between HU- and PI-treated patients (P = 0.004). A short-arm deletion of chromosome 17 was most frequently detected in HU-treated patients, while a long-arm trisomy of chromosome 1 and a monosomy 7q were seen in PI-treated patients. No TP53 mutation was discovered in the six patients studied (two HU-treated and four PI-treated). We conclude that these cytogenetic abnormalities are not linked to the natural history of the disease, but rather that they might be induced by the cytoreductive treatment.