Prognostic Value of BCR-ABL Transcript Amount for Early Relapse Detection in Chronic Myeloid Leukemia Patients Treated with Allogeneic Hematopoietic Stem Cell Transplantation.

The detection of BCR-ABL mRNA following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with relapse but not absolutely predictive. Early molecular relapse can be detected using real-time quantitative PCR (RQ-PCR) assay, which provides an accurate and reliable method of BCR-ABL expression evaluation. Using this method we analyzed 66 CML patients 3 months to 12 years (median 50 months) after allo-HSCT, who had BCR-ABL transcript measured in peripheral blood or bone marrow samples every 3, 6 and 12 months after allo-HSCT. The patients were analyzed at monthly intervals in the case of rising BCR-ABL transcript level. The median age at diagnosis and median age at time of allo-HSCT were 38 years (range, 16–55). Fifty three patients were in the first chronic phase, and 13 were in the second chronic phase. The median time from diagnosis to allo-HSCT was 8 months (range, 2.5–59). Eighty two percent of patients received allo-HSCT from HLA-identical siblings and 18% from unrelated donors. Transplant conditioning and GvHD prophylaxis were performed according to standard protocols. Quantification of BCR-ABL mRNA transcript was performed according to ‘Europe Against Cancer’ protocol. The median number of assays per patient was 6 (range, 3–16). According to the amount of BCR-ABL transcript after allo-HSCT, patients were allocated into 3 categories, including 35 patients with stable/low level of BCR-ABL transcript (below 0.005%), 11 patients with fluctuating-low level of BCR-ABL (0.005%–0.01%), and 18 patients with high level of BCR-ABL transcript (0.01%–0.1%). We found strong correlation between the amount of BCR-ABL transcript after allo-HSCT and probability of molecular relapse (6% vs. 9% vs. 28%, respectively) as well as relapse-free survival (median time to relapse: 134 months vs. 106 vs. 89, respectively). In the group of patients with high level of BCR-ABL transcript cytogenetic relapse was observed in 75%. In one case BCR-ABL level spontaneously fall down to a low-lewel expression within 6 months. One patient received donor lymphocyte infusion without response, and then was successfully treated with imatinib. RQ-PCR is valuable method to quantitate BCR-ABL expression in CML patients after allo-HSCT, allows monitoring the kinetics of BCR-ABL mRNA transcript amount and is useful in prediction of the hematologic relapse. RQ-PCR can successfully distinguish the group of patients with high risk of relapse from two groups without need for additional therapy (persistent disease/lack of disease).