Acute myeloid leukemia evolving from essential thrombocythemia in two patients treated with hydroxyurea

Abstract

Essential thrombocythemia (El) Is an uncommon myeloprollferatlve disorder, which is thought to develop from a multlpotent stem cell. Like other myeloprollferatlve diseases, ET is assoclated with an increased risk of development of acute leukemla (AL). However, the large majority of cases of leukemic transformation in ET are thought to be related to prior therapy, usually radioactive phosphorous or alkylatlng chemotherapy, and the development of AL In ET Is extremely rare In the untreated patient. in this report, two cases of ET which evolved into AL without prior exposure to radiation or alkylatlng agents, and which were treated with long-term hydroxyurea therapy, are described. The first case had cytogenetlc changes In the bone marrow suggestive of therapy-associated leukemia, and the second developed myelodysplastic syndrome on therapy which was llkely chemo-therapy-Induced and led to acute leukemia. Prolonged used of hydroxyurea In patients with ET may lead to therapy-associated acute leukemia.

Leukemic transformation with trisomy 8 in essential thrombocythemia: a report of four cases

“…reported myeloid blastic transformation of ET treated with hydroxyurea, and they reported an increased incidence of 17p deletion in those patients (3). Myeloid blastic transformation in ET with chromosome abnormalities including trisomy 8 have also been reported in cases treated with hydroxyurea (9, 10). One of our four patients with blastic transformation with trisomy 8 had been treated with hydroxyurea, and the other three patients had been treated with busulfan or MCNU.…”

“…Uozumi et al . summarized karyotype findings at blastic transformation of ET, and they found nine cases of trisomy 8 of 59 cases (15%) in which chromosome studies were performed (2–4, 9–12). After their report, one case of karyotype study at leukemic transformation was reported (13), but trisomy 8 was not found.…”

Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients

“…Firstly, whether asymptomatic and young ET patients should be treated and how, taking into account the known leukemogenic effect of cytotoxic agents. 28,29 Hydroxyurea does have leukemogenic potential, 29,30 a very important consideration when deciding whether or not to commit symptomatic younger patients with ET to continuous long-term therapy with this drug. The therapeutic effects of interferon in the treatment of ET include the effective control of thrombocytosis, reduction of splenomegaly and the control of disease-associated symptoms 31 but, although interferon is a nonleukemogenic agent, its cost and toxicity have prevented its widespread use.…”

Primäre Thrombozythämie: Diagnose und Therapie

“…Die Auffassungen reichen von völliger Unbedenklichkeit bis zur Empfehlung des vorsichtigen Einsatzes auch bei äl-teren Patienten [30][31][32][33][34][35]. Auf jeden Fall erhöht die konsekutive Anwendung von Busulfan und Hydroxyharnstoff das Leukämierisiko, so dass Busulfan nicht mehr angewendet werden soll.…”