Clinical value of quantitative long-term assessment of bcr-abl chimeric transcript in chronic myelogenous leukemia patients after allogeneic bone marrow transplantation

Background and Objectives. For purposes of therapeutic decision making, we used quantitative polymerase chain reaction (PCR) for molecular follow Up o f 55 patients with chronic myeloid leukemia (CML) in complete remission (CR ) after allogeneic bone marrow transplantation (BMT) from HLA compatible do nors. Design and Methods. A total of 402 bone marrow samples from 40 patients tra nsplanted in chronic phase (group 1) and 15 in accelerated/blastic phase (g roup 2) were analyzed by qualitative and quantitative PCR. Results. Regarding clinical outcome, 34/40 (85%) group 1 vs. 8/15 (54%) gro up 2 patients are alive. Only 1/40 (2.5%) group 1 patient relapsed, as agai nst 6/15 (40%) in group 2 (p = 0.0002). At qualitative FOR, 8/40 (19%) grou p 1 vs. 9/15 (60%) group 2 patients were positive, with a significantly gre ater total number of positive samples In group 2 (33/129, 27% vs. 18/273, 5 %; p<0.001). The probability of qualitative PCR positivity >1 year after BM T was significantly lower in group 1 patients (4/40 patients, 10% vs. 9/15 patients, 60%; p=0.01). At quantitative PCR, 4/8 (50%) group 1 patients wer e positive only once (< 400 transcripts/mu g RNA). In group 2, 9/15 (60%) p atients had 3 or more positive samples (always with >4,000 copies/mg RNA); therapeutic interventions (cyclosporin A discontinuation, temporary alpha-i nterferon or donor lymphocyte infusion) restored molecular remission in 4/9 (44%) cases. Interpretation and Conclusions. This study indicates that quantitative PCR could provide practical indications capable of directing therapeutic interv entions for transplanted CML patients, especially those transplanted in acc elerated/blastic phase, for whom intensive monitoring Is required. (C) 2000 , Ferrata Storti Foundation.