TY - JOUR
T1 - Diagnostic performance of the molecular BCR-ABL1 monitoring system may impact on inclusion of CML patients in stopping trials
AU - Spiess, Birgit
AU - Rinaldetti, Sébastien
AU - Naumann, Nicole
AU - Galuschek, Norbert
AU - Kossak-Roth, Ute
AU - Wuchter, Patrick
AU - Tarnopolscaia, Irina
AU - Rose, Diana
AU - Voskanyan, Astghik
AU - Fabarius, Alice
AU - Hofmann, Wolf Karsten
AU - Saußele, Susanne
AU - Seifarth, Wolfgang
N1 - Publisher Copyright:
© 2019 Spiess et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/3
Y1 - 2019/3
N2 - In chronic myeloid leukemia (CML), the duration of deep molecular response (MR) before treatment cessation (MR 4 or deeper, corresponding to BCR-ABL1 0.01% on the International Scale (IS)) is considered as a prognostic factor for treatment free remission in stopping trials. MR level determination is dependent on the sensitivity of the monitoring technique. Here, we compared a newly established TaqMan (TM) and our so far routinely used LightCycler (LC) quantitative reverse transcription (qRT)-PCR systems for their ability to achieve the best possible sensitivity in BCR-ABL1 monitoring. We have comparatively analyzed RNA samples from peripheral blood mononuclear cells of 92 randomly chosen patients with CML resembling major molecular remission (MMR) or better and of 128 CML patients after treatment cessation (EURO-SKI stopping trial). While our LC system utilized ABL1, the TM system is based on GUSB as reference gene. We observed 99% concordance with respect to achievement of MMR. However, we found that 34 of the 92 patients monitored by TM/GUSB were re-classified to the next inferior MR log level, especially when LC/ABL1-based results were borderline to thresholds. Thirteen patients BCR-ABL1 negative in LC/ABL1 became positive after TM/GUSB analysis. In the 128 patients included in the EURO-SKI trial identical molecular findings were achieved for 114 patients. However, 14 patients were re-classified to the next inferior log-level by the TM/GUSB combination. Eight of these patients relapsed after treatment cessation; two of them were re-classified from MR 4 to MMR and therefore did not meet inclusion criteria anymore. In conclusion, we consider both methods as comparable and interchangeable in terms of achievement of MMR and of longitudinal evaluation of clinical courses. However, in LC/ABL1 negative samples, slightly enhanced TM/GUSB sensitivity may lead to inferior classification of clinical samples in the context of TFR.
AB - In chronic myeloid leukemia (CML), the duration of deep molecular response (MR) before treatment cessation (MR 4 or deeper, corresponding to BCR-ABL1 0.01% on the International Scale (IS)) is considered as a prognostic factor for treatment free remission in stopping trials. MR level determination is dependent on the sensitivity of the monitoring technique. Here, we compared a newly established TaqMan (TM) and our so far routinely used LightCycler (LC) quantitative reverse transcription (qRT)-PCR systems for their ability to achieve the best possible sensitivity in BCR-ABL1 monitoring. We have comparatively analyzed RNA samples from peripheral blood mononuclear cells of 92 randomly chosen patients with CML resembling major molecular remission (MMR) or better and of 128 CML patients after treatment cessation (EURO-SKI stopping trial). While our LC system utilized ABL1, the TM system is based on GUSB as reference gene. We observed 99% concordance with respect to achievement of MMR. However, we found that 34 of the 92 patients monitored by TM/GUSB were re-classified to the next inferior MR log level, especially when LC/ABL1-based results were borderline to thresholds. Thirteen patients BCR-ABL1 negative in LC/ABL1 became positive after TM/GUSB analysis. In the 128 patients included in the EURO-SKI trial identical molecular findings were achieved for 114 patients. However, 14 patients were re-classified to the next inferior log-level by the TM/GUSB combination. Eight of these patients relapsed after treatment cessation; two of them were re-classified from MR 4 to MMR and therefore did not meet inclusion criteria anymore. In conclusion, we consider both methods as comparable and interchangeable in terms of achievement of MMR and of longitudinal evaluation of clinical courses. However, in LC/ABL1 negative samples, slightly enhanced TM/GUSB sensitivity may lead to inferior classification of clinical samples in the context of TFR.
UR - https://www.scopus.com/pages/publications/85063345854
U2 - 10.1371/journal.pone.0214305
DO - 10.1371/journal.pone.0214305
M3 - Article
C2 - 30897165
AN - SCOPUS:85063345854
SN - 1932-6203
VL - 14
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e0214305
ER -