Abstract
Purpose: Previously, we demonstrated the positive impact of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation (SCT) in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) (Blood2005;105:3449). Here, we analyzed for risk factors that affect transplantation outcome, and focused particularly on the prognostic relevance of minimal residual disease (MRD) during treatment course.
Patients and Methods: Fifty-two consecutive adults with Ph-positive ALL who completed SCT following imatinib therapy were enrolled in this prospective study. MRD assessment was performed using real-time quantitative polymerase chain reaction.
Results: Forty-three (87.8%) of the 49 evaluable patients showed a decrease in MRD after imatinib therapy. Molecular remission rates were 18.4% and 44.4% after the first and second imatinib cycles, respectively. Forty-eight (92.3%) of the 52 patients received SCT during first complete remission. With a median follow-up of 42 months after SCT, the actuarial 3-year relapse and disease-free survival (DFS) rates were 22.9% ± 6.6% and 67.3% ± 7.2%, respectively. An MRD level of ≥ 10−3 after the first imatinib cycle was found to be the most powerful predictor of relapse (47.5% ± 14.3% versus 11.4% ± 6.4%, P = .009) and DFS (45.0% ± 13.2% versus 80.9% ± 8.0%, P = .016). The presence of chronic graft-versus-host disease was also found to be associated with a lower relapse (5.3% ± 5.1% versus 37.6% ± 10.8%, P = .029) and better DFS (82.0% ± 9.5% versus 62.4% ± 10.8%, P = .039).
Conclusion: In the setting of allogeneic SCT following imatinib therapy, prospective MRD monitoring may allow us to identify subgroups of Ph-positive ALL patients at high risk of relapse at an earlier treatment stage.
Real-time quantitative PCR for detection of minimal residual disease before allogeneic stem cell transplantation predicts outcome in children with acute lymphoblastic leukemia
