Quantification of minimal residual disease in patients with BCR-ABL-positive acute lymphoblastic leukaemia using quantitative competitive polymerase chain reaction

We analysed 20 patients with BCR-ABL-positive acute lymphoblastic leukaemia (ALL) by quantitative competitive polymerase chain reaction (QC-PCR to stu dy the kinetics of the leukaemic clone. Consecutive samples of 16 patients (minor-bcr, n=10: major-bcr, n=6) were analysed after conventional chemothe rapy and/or bone marrow transplantation (BMT). DNA competitor templates co- amplifying with either p210 or p190 BCR-ABL cDNA were used for quantificati on of leukaemia-specific BCR-ABL mRNA. In all samples, total ABL transcript s were measured as internal control, and the percentage of BCR-ABL/ABL mole cules was calculated. Following induction chemotherapy the number of BCR-AB L transcripts was reduced by a maximum of 2-3 logs. In most patients, addit ional chemotherapy did not lead to further reduction of BCR-ABL mRNA. In tw o patients, conventional chemotherapy plus autologous BRIT in complete haem atological remission resulted in a total reduction of the transcript level of more than 3 logs. In two other patients, allogeneic BRIT caused a transi ent reduction of the BCR-ABL transcripts below the detection level of our m ethod (<1 blast cell in 10(5) normal cells) for a period of 7 and 11 months , respectively. The achievement of PCR negativity did not guarantee sustain ed remission. Both patients relapsed and BCR-ABL transcript levels rose by more than 1 log prior to frank relapse. Our data demonstrate that quantific ation of BCR-ABL mRNA allows the evaluation of the dynamics of the leukaemi c clone and thus is valuable for the evaluation of minimal residual leukaem ia following Various therapies and the early detection of increasing BCR-AB L transcripts prior to relapse.