BACKGROUND:
Philadelphia chromosome (Ph)‐positive B‐lymphoblastic leukemia exhibits immunophenotypic, karyotypic, and molecular genetic heterogeneity. The prognostic significance of these parameters was assessed in the context of intensive tyrosine kinase inhibitor (TKI)‐based chemotherapy.
METHODS:
The authors studied 65 adult patients with Ph‐positive acute lymphoblastic leukemia (ALL) who received treatment with TKI‐based therapy, correlated their clinicopathologic heterogeneity with patient outcome, and compared the findings with those from 60 adult patients with diploid B‐cell ALL who received similar chemotherapy without a TKI.
RESULTS:
Ph‐positive ALL was associated with older age (P = .01), the common‐B immunophenotype characterized by a greater frequency of CD13 (alanine aminopeptidase) coexpression (P = .004), CD66c (carcinoembryonic antigen‐related cell adhesion molecule 3) expression (P = .007), and CD25 (interleukin‐2 receptor alpha chain) expression (P < .001) and with a lower frequency of CD15 (3‐fucosyl‐N‐acetyl‐lactosamine) expression (P < .001). Conventional karyotypic analyses indicated that the Ph chromosome was the sole abnormality in 19 patients (30%), was present with other aberrancies in 43 patients (65%), and was absent (detectable only by fluorescence in situ hybridization [FISH] or quantitative reverse transcriptase‐polymerase chain reaction [RT‐PCR] analysis) in 3 patients (5%). The presence of the breakpoint cluster region–v‐Abelson murine leukemia viral oncogene homolog fusion gene (BCR‐ABL) was confirmed in all patients by FISH or RT‐PCR (the 190‐kDa protein [p190] construct was present in 49 patients [77%], and the p210 fusion transcript construct was present in 15 patients [23%]). The presence of a supernumerary Ph chromosome was correlated with a higher incidence of CD20 (B‐lymphocyte antigen, nonglycosylated phosphoprotein) expression (P < .001), whereas the p210 construct was correlated with aberrant CD25 expression (P = .05). Outcomes were not influenced by the degree of karyotypic complexity (including the presence or absence of a supernumerary Ph chromosome), CD20 expression, or myeloid antigen expression (CD13, CD33 [myeloid lineage transmembrane receptor], CD66c). CD25 expression was associated with inferior survival in univariate analysis (P = .051) but not in multivariate analysis (P = .092).
CONCLUSIONS:
In the context of intensive, TKI‐based chemotherapy, the immunophenotypic, karyotypic, and molecular heterogeneity of Ph‐positive ALL no longer influences outcome. Cancer 2011. © 2011 American Cancer Society.