Background: Therapeutic options in Philadelphia chromosome-positive chronic myelogenous leukemia (Ph-positive CML) in chronic phase include allogeneic stem cell transplantation (SCT) and treatments other than allogeneic SCT. The choice of therapy often depends on the mortality risk of allogeneic SCT. Delaying SCT until the disease demonstrates resistance to other strategies (e.g., imatinib mesylate or interferon-alpha) entails the risk of the development of a sudden blastic phase, which may not permit enough time to perform a SCT.
Methods: The current study was performed to define the incidence and patterns of sudden-onset blastic-phase CML in relation to the risk inherent in delaying allogeneic SCT. Of a study group of 1286 patients who were referred in early chronic-phase CML between 1981-2001 and who received therapies other than allogeneic SCT, 1093 patients had regular follow-up at the study institution. A sudden onset of blastic phase was defined as having its onset within 3 months from a previously documented complete hematologic response.
Results: Among the 1093 patients, 183 patients developed blastic-phase disease, which was of sudden onset in 46 patients (25%; 4% of the total). The incidence of sudden blastic phase was 0.4% in the first year, 1.8% in the second year, and 2.6% in the third year. Patients with sudden blastic-phase disease were found to have more often low-risk features at the time of presentation, including low incidences of blasts and thrombocytosis. Sudden blastic-phase CML was found to be associated with a higher incidence of lymphoid blastic morphology (67% vs. 22%; P < 0.0001), which resulted in a higher response rate to blastic-phase therapy (70% vs. 29%; P < 0.0001) and significantly longer survival from the onset of blastic-phase disease (median of 12 months vs. 6 months; P < 0.01). Twenty-four of the 42 patients with sudden blastic-phase disease who were treated at the M. D. Anderson Cancer Center were able to undergo allogeneic SCT in second chronic phrase (n = 13) or transformed phase (n = 11); at the time of last follow-up, 6 patients were alive without evidence of disease at a median of 18 months.
Conclusions: The low rates of sudden blastic transformation in the first 3 years of the course of disease for CML and the salvage rate of these patients with allogeneic SCT should be considered in relation to the transplantation mortality in patients with early chronic-phase disease and the early promising results with imatinib mesylate therapy.
Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11477