IS TREATMENT WITH HYDROXYUREA LEUKEMOGENIC IN PATIENTS WITH ESSENTIALTHROMBOCYTHEMIA - AN ANALYSIS OF 3 NEW CASES OF LEUKEMIC TRANSFORMATION AND REVIEW OF THE LITERATURE

From 1981 to 1995, we diagnosed, followed and treated at our instituti on fifty-eight cases of essential thrombocythemia (ET), using hydroxyu rea (HU) as first-line therapy in these patients. Three patients who w ere continuously receiving HU had a leukemic transformation after a ch ronic phase of respectively 47, 81 and 90 months. One patient develope d an acute leukemia with minimal myeloid differentiation (AML MO) and soon died of refractory disease; the second developed a refractory ane mia with excess blasts in transformation (t-RAEB) and survived one yea r; the third patient developed a chronic myelomonocytic leukemia (CMML ) and is alive at 21 months. The two former patients had complex nonra ndom bone marrow karyotypic abnormalities, suggestive of therapy-relat ed leukemia, whereas the latter one had a normal karyotype throughout the chronic and leukemic phase. These findings, together with recently published results on myeloproliferative disorders (MPD) treated with HU, suggest that this drug might be as leukemogenic as other myelosupp ressive therapies in patients with ET. Longterm HU therapy should be r eserved for patients in whom the treatment benefits obviously outweigh the risk of inducing leukemia.