Leukaemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms: are Asian patients different?

Background: Leukaemic transformation (LT) is rare in the natural history of Philadelphia(Ph) chromosome-negative myeloproliferative disorders (MPD), and has a dismal prognosis. Little literature is available on Asian patients. Aims: The aim of this study is to report a single institution experience of Asian patients who developed acute leukaemia after being diagnosed and treated for Ph chromosome-negative MPDs, and to compare the findings of this series with similar studies from the literature. Methods: Patients were recruited from the MPD registry of Singapore General Hospital, Department of Hematology. Clinical data including treatment modalities and duration of use in myeloproliferative phase, latency to LT, characteristics of leukaemia, chemotherapy administered and survival after LT were examined. Results: Over a 29-year period from 1980 to 2009, there were 22 Asian patients with LT of Ph chromosome-negative MPD of which four had polycythaemia vera (PV), nine had essential thrombocythaemia (ET), seven had myelofibrosis (MF) and two had unspecified MPD at diagnosis. Primary treatment modality was Hydroxyurea (HU) during MPD phase. Median latency to LT was 14 years for PV, 10 years for ET and 1 year for MF. Median age at LT diagnosis was 67.5 years. Nine patients had complex cytogenetics, with abnormalities of chromosomes 5 and 7 being common. Overall, median survival was 2 months after LT. Eight patients who received induction chemotherapy had a median survival of 2.5 months. Survival was independent of MPD type and treatment administered. None received stem cell transplantation. Conclusions: LT of Ph chromosome-negative MPD is rare and uniformly fatal. Despite chemotherapy, survival was poor, and patients succumbed to refractory disease and infections. Asian patients did not have a more favourable outcome. It remains to be investigated whether upfront stem cell transplant may be a treatment option.