Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan.
Eighty-three patients with various chronic myeloproliferative disorders [polycythemia vera (PV), essential thrombocytosis (ET), idiopathic myelofibrosis (IMF)] were analyzed for the occurrence of acute myeloid leukemia (AML) and myelodysplasia (MDS) during treatment with hydroxyurea (HU) alone or HU following treatment with busulphan (BU). A total of 58 patients (29 PV, 14 ET, 12 IMF, 3 unclassified) had been treated with HU. Thirty-five of these patients had been treated with HU alone whereas 18 patients had received both HU and BU. The follow-up period was 7.8 years. Twenty-five patients had not been treated with HU. In this patient group, 4 patients had been treated with BU. The follow-up period was 10.5 years. In the HU-treated group (n = 58) 7 patients developed AML and 5 patients MDS. Five of the 12 patients had been treated with HU alone, and 4 patients had received both HU and BU. In the non-HU-treated group (n = 25) 1 patient with PV developed acute myeloid leukemia (AML). This patient had only been treated with phlebotomies. It is concluded that treatment with HU is leukemogenic, with an incidence of AML and MDS of approximately 14% when used alone. The incidence is markedly increased to about 30% when HU is preceded by treatment with BU. HU is not recommended for use in younger patients, in whom non-leukemogenic agents such as alpha-interferon and anagrelide should be used instead.
Nielsen
Iben
I
Department of Hematology L, Rigshospitalet University Hospital, Copenhagen, Denmark.
Hasselbalch
Hans Carl
HC
D000208:Acute Disease; D000477:Alkylating Agents / Q000009:adverse effects*; D002066:Busulfan / Q000009:adverse effects*; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects*; D007938:Leukemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced*; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000235:genetics*; D010677:Philadelphia Chromosome; D055728:Primary Myelofibrosis / Q000139:chemically induced; D012189:Retrospective Studies; D016019:Survival Analysis
D000477:Alkylating Agents; D002066:Busulfan; D006918:Hydroxyurea