Flow Cytometry Immunophenotypic, Molecular and Cytogenetic Characteristics of Philadelphia (Ph)-Positive B Lymphoblastic Leukemia
J Jaso, K Cunningham, LJ Medeiros, JL Jorgensen, D Thomas, SA Wang. University of Texas, Houston; UTMB, Houston; UT MD Anderson, Houston
Background: Ph-positivity defines a subgroup of B lymphoblastic leukemia(B-ALL) with a poor prognosis. The clinical, molecular, cytogenetic and immunophenotypic characteristics in relation to prognosis have not been fully elucidated.
Design: We retrospectively analyzed 69 Ph+ B-ALL cases diagnosed and treated (intensive chemotherapy plus tyrosine kinase inhibitors) at the same hospital. Flow cytometry immunophenotyping(FCI) was conducted initially using antibodies designed for acute leukemia work-up, and further analyzed by a minimal residual disease panel designed for B-ALL. Conventional karyotyping, FISH for BCR/ABL1, and real time quantitative PCR for BCR-ABL1 were performed on majority of the patients.
Results: There were 35 women and 34 men, with a median age of 54 years. 7 patients presented as B-ALL blast crisis of chronic myelogenous leukemia(CML), and the remaining 62 patients had de novo disease. t(9;22) was a sole abnormality in 23; and with other abnormalities in 46 cases including -7(n=12), +8(n=2), and del(9)(p21)(n=3). No cases had an additional copy of the Ph chromosome. RT-PCR showed p190 fusion transcripts in 49, and p210 in 17 cases. FCI showed an early precursor B-immunophenotype with CD34+(99%), CD10+(97%), and Tdt+(100%), and cytoIgM-negative(74%). CD13(70%), CD33(64%), and CD66c(77%) coexpression were frequent, but not CD15(5%). CD25 coexpression was detected in 45/61(74%) cases. With a median follow-up of 16 months, the overall survival(OS) was 25 months. There was no difference in OS between cases with p190 versus p210 fusion transcripts(p=0.57); t(9;22) alone or with other abnormalities(p=0.81); with or without -7(p=0.46); CD13/CD33 positive or negative by FCI (p=0.62). However, patients with CML blast crisis had an inferior OS to patients with de novo disease (OS 6.5 vs. 25 months, p=0.02); and cases with CD25 coexpression showed a shorter OS than CD25-negative cases (OS 24 months vs. not reached, p=0.02).
Conclusions: Cases of Ph+ B-ALL show genetic, molecular and immunophenotypic heterogeneity. Patients who have B-ALL as a result of CML blast crisis have an inferior OS to patients with de novo disease. The BCR breakpoint was not prognostically significant. Myeloid antigen coexpression is very common in Ph+ B-ALL but lacks prognostic significance. Our study showed that CD25 expression is prognostically important, and should be considered as a major prognostic factor for Ph+ B-ALL.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 184, Tuesday Afternoon