Blast Phase in Chronic Myelogenous Leukemia (CML) Is Skewed towards Unusual Blast Types in Patients Treated with Tyrosine Kinase Inhibitors (TKIs): A Comparative Study of 67 Cases
Andrew Rand, Jennifer Crow, Joseph O Moore, Anand S Lagoo. Duke University Medical Center, Durham, NC
Background: The abnormal proliferation of clonal hematopoietic stem cells in CML is largely driven by the abnormal chimeric protein BCR/ABL with its constitutively active tyrosine kinase function. The introduction of TKIs such as Imatinib (Gleevec) circa 2000 has revolutionized CML treatment, greatly improving overall survival. Blast phase (or blast transformation) is the terminal event in most patients with CML, including those treated with TKIs.
Design: From the pathology database we identified 67 cases of blast phase CML diagnosed at our Institution between 1991 and 2011. The basic demographic and clinical information, the temporal sequence of blast phase development, and the immunophenotypic and pathological characteristics of blasts in each case were reviewed.
Results: 44 of 67 patients were treated by traditional agents such as hydroxyurea and/or interferon while 23 patients received TKIs. The median age of patients in the two groups was virtually identical (50.9 and 50.7 years), even though there was a significantly higher proportion of males in the TKI treated group (M:F of 17:6 in TKI treated vs 22:22 in pre-TKI group, p = 0.0362, Fisher exact). The median interval from CML diagnosis to blast phase was not significantly different between the two groups (20.8 vs 18.3 months, p = 0.8, t test). Extramedullary presentation of blast phase in spleen, lymph nodes, or other sites occurred at similar low frequency in pre-TKI and TKI groups (4 and 2 cases, respectively). The blast phase was “usual” in 41 of 44 (93%) patients in the pre-TKI era: lymphoblastic (7 cases) or myeloblastic (34 cases). Only three cases showed “unusual” types of blasts: one case each of megakaryoblasts, erythroblasts, and a lymph node involved by B- and T-lymphoblasts. In contrast, only 13 of 23 (56.5%) cases in the TKI era were “usual”: 5 lymphoblastic and 8 myeloblastic. The remaining 43.5% were either monoblastic (3 cases), biphenotypic (3 cases), basophilic (2 cases), eosinophilic or megakaryoblastic (1 each).
Conclusions: Unusual forms of blast phase occur more frequently in CML patients treated with TKIs compared to prior therapy.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 219, Wednesday Morning