Is treatment with hydroxyurea leukemogenic in patients with essential thrombocythemia? An analysis of three new cases of leukaemic transformation and review of the literature

Abstract

From 1981 to 1995, we diagnosed, followed and treated at our institution fifty-eight cases of essential thrombocythemia (ET), using hydroxyurea (HU) as first-line therapy in these patients. Three patients who were continuously receiving HU had a leukemic transformation after a chronic phase of respectively 47, 81 and 90 months. One patient developed an acute leukemia with minimal myeloid differentiation (AML MO) and soon died of refractory disease; the second developed a refractory anemia with excess blasts in transformation (t-RAEB) and survived one year; the third patient developed a chronic myelomonocytic leukemia (CMML) and is alive at 21 months. The two former patients had complex nonrandom bone marrow karyotypic abnormalities, suggestive of therapy-related 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 myelosuppressive therapies in patients with ET. Longterm HU therapy should be reserved for patients in whom the treatment benefits obviously outweigh the risk of inducing leukemia.

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

“…6,7 Recently, it has also been reported that long-term treatment with HU may favor an evolution of ET into MDS/AML, 8 marked by a 17p deletion (17p−) with loss of one TP53 allele, vacuolated neutrophils and presentation of the Pelger-Huét anomaly. Even if this reported association still needs to be proved, 18,19 four of our eight AMLs having evolved from ET occurred in subjects treated with HU and three of them developed a 17p−. In every case FISH with the p53 DNA probe detected only one red signal, confirming loss of one TP53 allele.…”

Hydroxyurea therapy for sickle cell disease in community‐based practices: A survey of Florida and North Carolina hematologists/oncologists

“…However, opinion experts have remained divided concerning the true leukemogenic potential of HU for this patient population [17,[20][21][22][23][24]; thus uncertainty remains today [25]. In a clinical trial of HU therapy for children and young adults with SCD, there were no cases of leukemia with a mean follow-up observation time of 3 years [26].…”

Essential thrombocythemia terminating in pure erythroleukemia

“…The neoplastic clones in CMPDs are able to differentiate into the cell lines that predominate the chronic phase but also into other lineages in the blastic phases of disease. Thus, in ET, in which the megakaryocytes and platelet production dominate the chronic phase, most secondary leukemias were of myeloid differentiation [7,8,10,11]. In only a few patients, ET evolved into megakaryoblastic leukemia [8,11,12].…”