Outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia

Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) re presents the most common cytogenetic abnormality in adult ALL. It is found in 15% to 30% of patients, and its incidence increases with age. As in chil dren, prognosis in Ph-positive adult ALL is poor. No therapeutic approach h as had substantial impact on its unfavorable course. We analyzed the charac teristics and outcome of newly diagnosed adults with Ph-positive ALL treate d at the M. D. Anderson Cancer Center between 1980 and 1997. The diagnosis of patients was based on typical morphological and immunophenotypic criteri a of marrow aspirate and biopsy specimens. Cytogenetic and molecular studie s were also performed. A total of 67 patients were included in this study. From 1980 until 1991, 38 patients with Ph-positive ALL were treated with vi ncristine, Adriamycin, and dexamethasone (VAD), or with acute myeloid leuke mia (AML)-like induction protocols. Since 1992 a total of 29 patients recei ved induction therapy with an intensified treatment protocol, called "hyper -CVAD". The outcome of patients treated with standard and intensified treat ment regimens was compared and results of our institution contrasted with d ata obtained from other centers. Ph-positive ALL was present in 67 of 498 patients with newly diagnosed ALL (13%). Patients with Ph-positive ALL had a higher median age (44 versus 34, P=0.007), higher median white blood cell (WBC) counts at presentation (25 versus 8, P=0.0002), and higher peripheral median percentage of blast count s (63 versus 40, P=0.023). FAB subtype L2 (70% versus 49%, P=0.001) and CAL LA-positive pre-B immunophenotype (75% versus 37%, P <0.001) predominated a mong Ph-positive ALL. Myeloid marker coexpression was more frequent in Ph-p ositive ALL when compared with Ph-negative ALL (52% vs. 27% for CD13, P<0.0 01, and 44% vs. 27% for CD33, P=0.005). Among patients treated with hyper-C VAD, the complete remission (CR) rate was 90% versus 55% (P=0.002) with pre -hyper-CVAD regimens (VAD and AML-like induction protocols), the median CR duration was 43 weeks versus 32 weeks (P >0.5), median disease-free surviva l (DFS) was 42 weeks versus 29 weeks (P=0.008), and median survival was 66 weeks versus 45 weeks (P 20.5). Patients with hyperdiploid Ph-positive ALL on hyper-CVAD therapy achieved significantly longer CR duration and DFS tha n hypo- and pseudodiploid cases (59 weeks versus 42 and 31 weeks, P=0.02 an d 0.04, respectively). In contrast, patients treated with regimens prior to hyper-CVAD had significantly shorter CR duration (21 weeks versus 33 and 2 9 weeks, P=0.03) and DFS with hyperdiploid karyotypes when compared to pseu dodiploid and hypodiploid cases (16 weeks versus 30 and 13 weeks, P=0.008). In conclusion, our results demonstrate improved response rate and DFS with current intensive regimens (hyper-CVAD) in patients with Ph-positive ALL, but no advantage in overall survival.