The Extent of Minimal Residual Disease Reduction After the First 4-Week Imatinib Therapy Determines Outcome of Allogeneic Stem Cell Transplantation in Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

BACKGROUND: Previously, the authors demonstrated the positive impact of imatinib on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). Here, the authors analyzed for risk factors that affect transplantation outcome, and they focused particularly on the prognostic relevance of minimal residual disease level at each treatment stage. METHODS: Fifty-two patients with newly diagnosed Ph-positive ALL who completed allogeneic stem cell transplantation following imatinib therapy were enrolled in this study. For minimal residual disease monitoring, 548 marrow samples were analyzed by a real-time quantitative polymerase chain reaction assay. RESULTS: After the first 4-week imatinib therapy, 11 patients (21.2%) achieved molecular remission, and the remaining 41 patients had a reduction in BCR-ABL transcript levels (median, 3.21 log) from baseline value, The frequency of achieving a reduction in BCR-ABL transcript levels of at least 3 log at this stage was 36 (69.2%). Forty-eight (92.3%) of the 52 patients received stem cell transplantation during first complete remission. With a median follow-up of 49 months after stem cell transplantation, the 4-year relapse rate and disease-free survival rate were 21.2% and 69.8%, respectively. A reduction in BCR-ABL transcript levels of at least 3 log after the first 4-week imatinib therapy was identified as the most powerful predictor of lower relapse (12.1% vs 45.1%, P = .011) and better disease-free survival (82.1% vs 41.7%, P = .009) rates. CONCLUSIONS: Prospective assessment of the extent of minimal residual disease reduction after the first 4-week imatinib therapy may allow the authors to identify subgroups of Ph-positive ALL transplants at high risk of relapse. Cancer 2009;115:561-70. (c) 2008 American Cancer Society.