Incidence, clinical features and prognostic relevance of BCR-ABL fusion oncogene in acute lymphoblastic leukaemia patients
Authors: Mariam Faiz, Qazi Javed Iqbal, Syed Waqar Haider
Journal: Clinical Cancer Research (2007)

C70   BACKGROUND: Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) is a common cytogenetic abnormality in ALL and found in 25% to 50% in adult patients and 3% to 5% in paediatric patients. Its is associated with poor outcome in children as well as in adults. This preliminary study is reported to define the frequency of prevalence of the BCR-ABL fusion subtypes in our ALL patients by reverse transcription-PCR (RT-PCR) and to ascertain the prognostic significance of t9:22 translocation along with other characteristics. PATIENTS AND METHODS: One hundred five adult and fifty five paediatric ALL patients treated at our center between 2004 and 2006 comprised the study group. The diagnosis of patients was based on typical morphological criteria of marrow aspirate and biopsy specimens. Adult ALL patients were treated with induction regimen consisting of a combination of vincristine, prednisone, daunorubicin, L-asparginase and cyclophosphomide followed by courses of early, interim and late intensification and CNS prophylaxis and consolidation I, reinduction, consolidation II, maintenance, and central nervous system (CNS)  prophylaxis. RESULTS: Among the adult patients included in this study,  BCR-ABL  fusion oncogene was present in 47 of 105 patients (45%) while in children (1-15 years age) prevalence was 25%. High incidence of BCR-ABL fusion oncogene was observed in paediatric patients. The number  of adult patients within 3 age groups (  50  years) differed significantly between BCR-ABL +  and BCR-ABL -  patients ( P  = .001). The median age was significantly higher  in the BCR-ABL +  group (30 versus 15 years;  P  = .0001). BCR-ABL +  patients were also characterized by higher median white blood  cell (WBC) counts (180000/µL versus 23000//µL  P  = .0001). A statistically significant difference in the initial response  rate to induction therapy was observed. A complete remission  (CR) was achieved in 49 of 80 (61%) BCR-ABL -  patients and 31 of 80 (38%) BCR-ABL +  patients ( P  = .001). The BCR-ABL -  patients achieving complete continued remission were only 10% and none of the BCR-ABL +  patients maintained a CR further to induction therapy. With the available therapeutic protocol, the presence of a BCR-ABL fusion predicted ( P  = .0001)  a lower survival. The estimates of event-free survival and overall survival (±SE) two years after diagnosis in the adult patients were 20 percent and 30 percent, respectively. Age, initial leukocyte count, were found to have a significant effect on the outcome of treatment. The probability of overall survival at 2 years after diagnosis was 0.30 (± 0.03 SE) in BCR-ABL -  (n = 49; median survival, 360 days) versus 0.15 (± 0.03 SE) in BCR-ABL +  patients (n = 31; median survival, 240 days; P = .0001). The DFS of BCR-ABL +  patients remains markedly low (with CALGB protocol at 2 years, 0.08 ± 0.03 SE). Multivariate analysis confirmed WBC count and BCR-ABL result  as an independent prognostic factors CONCLUSION: This study emphasizes that BCR-ABL gene fusion is an independent prognostic factor in ALL patients. Identification and characterization of this genetic entity in adult ALL at diagnosis is crucial for understanding the nature of adult acute lymphoblastic leukaemia and for deciding optimal treatment