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Prognostic Factors for Thrombosis, Bleeding, Myelofibrosis, and Leukemia

Chor-Sang Chim, MD, FRCP, FACP; Yok-Lam Kwong, MD, FRCP, FRCPath; Albert Kwok-Wei Lie, FRCP, FRCPath; Siu-Kwan Ma, FRCP, FRCPath; Chi-Chung Chan, MRCP; Lap-Gate Wong, MRCP; Bonnie Chi San Kho, MRCP; Harold-Kwok Lee, MRCP; Joycelyn Pui-Yin Sim, MRCP; Cheuk-Hung Chan, FRCP; Joyce Chee-Wun Chan, FRCP; Yiu-Ming Yeung, FRCP; Martin Law, PhD; Raymond Liang, MD, FRCP, FRACP

Arch Intern Med. 2005;165:2651-2658.

Background  Essential thrombocythemia (ET) is a clonal myeloproliferative disease associated with thrombohemorrhagic complications and myeloid transformation to diseases such as myelofibrosis and acute myeloid leukemia.

Methods  A multicenter study was conducted among 231 consecutive Chinese patients with ET. The literature about leukemogenic risk associated with the use of hydroxyurea therapy was reviewed.

Results  The median patient age was 65 years. Thrombosis rates at and after diagnosis of ET were comparable to those of white patients, but bleeding rates at and after diagnosis were much lower. The projected 10-year thrombosis-free, bleeding-free, and overall survival rates were 66%, 83%, and 80%, respectively. There were no deaths among patients 60 years or younger during a maximum follow-up of 15 years, and splenomegaly at diagnosis of ET appeared to protect against thrombosis. In multivariate analysis, advanced age predicted inferior 10-year thrombosis-free and overall survival, and male sex predicted inferior bleeding-free survival. Half the deaths were related to ET. The probability of myelofibrosis transformation was 9.7% at 10 years. Prior myelofibrosis (P = .008) and the use of melphalan treatment (P = .002) were risk factors for acute myeloid leukemia evolution.

Conclusions  Essential thrombocythemia is a benign disease of older persons. Chinese patients have a low risk of bleeding, and prior myelofibrosis is a major risk factor for evolution to acute myeloid leukemia. Leukemic transformation with hydroxyurea therapy alone is rare and warrants further prospective studies.

Author Affiliations: Departments of Medicine (Drs Chim, Kwong, Lie, and Liang), Pathology (Dr Ma), and Clinical Oncology (Dr Law), Queen Mary Hospital, University of Hong Kong; Department of Medicine, Queen Elizabeth Hospital (Drs C.-C. Chan and C.-H. Chan); Department of Medicine, Tuen Mun Hospital (Drs Wong and Yeung); Department of Medicine, Pamela Youde Nethersole Hospital (Drs Kho, Sim, and J. C.-W. Chan); and Department of Medicine, Princess Margaret Hospital (Dr Lee); Hong Kong.

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