Cytogenetic abnormalities and leukemic transformation in hydroxyurea-treated patients with Philadelphia chromosome negative chronic myeloproliferative disease.
Eighty-one consecutive hydroxyurea-treated patients with Philadelphia (Ph) chromosome negative chronic myeloproliferative disease were followed prospectively from 1981 to 1989; 35 of them had polycythemia vera, 32 had essential thrombocythemia, 12 had myelofibrosis, and 2 had myeloproliferative syndromes. The 81 patients were treated with hydroxyurea for a total of 3,804 months during the observation time. Only three patients had been treated with alkylating agents or 32P before start of hydroxyurea treatment. Four patients transformed into acute myeloid leukemia or myelodysplastic syndromes; three of these patients had essential thrombocythemia, and one had a myeloproliferative syndrome. Two patients died of solid cancers. Five out of 53 evaluable patients (9%) had pretreatment clonal cytogenetic abnormalities involving chromosomes 1, 9, 20, and 21. At follow-up, during or after hydroxyurea treatment, 15% had cytogenetic abnormalities, an unexpectedly low frequency compared to the previously reported frequency in patients with polycythemia vera treated with alkylating agents. None of our patients who developed cytogenetic clonal changes during hydroxyurea therapy had polycythemia vera. However, follow-up is too short to draw any conclusions about the mutagenic potential of hydroxyurea compared to alkylating agents.
Department of Medicine, University Hospital, Umeå, Sweden.
E
E
Löfvenberg
I
I
Nordenson
A
A
Wahlin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002908:Chronic Disease; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects* / Q000627:therapeutic use; D007938:Leukemia / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010677:Philadelphia Chromosome; D011289:Preleukemia / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology
D006918:Hydroxyurea