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- Title
Serial minimal residual disease (MRD) analysis as a predictor of response duration in Philadelphia-positive acute lymphoblastic leukemia (Ph<sup>+</sup>ALL) during imatinib treatment.
- Authors
Scheuring, U.J.; Pfeifer, H.; Wassmann, B.; Brück, P.; Gehrke, B.; Petershofen, E.K.; Gschaidmeier, H.; Hoelzer, D.; Ottmann, O.G.
- Abstract
Patients with refractory or relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) rarely have prolonged responses to salvage therapy, including imatinib, resulting in a short opportunity for potentially curative stem cell transplantation. To identify minimal residual disease (MRD) parameters predictive of imminent relapse, we quantitated Bcr-Abl expression by real-time PCR in peripheral blood (PB) and bone marrow (BM) of 24 Ph+ALL patients after achieving a complete response and MRD minimum. The ratio of Bcr-Abl and glyceraldehyde-3-phosphate dehydrogenase copies, magnitude of increase and velocity of increase were evaluated regarding subsequent time intervals to relapse, death or censoring. High Bcr-Abl levels ?5 × 10-4 in PB (n=23) and ?10-4 in BM (n=18) were significantly associated with short time periods to relapse. Bcr-Abl increases >2 logarithmic units (log) in PB, but not in BM preceded short-term relapse. The velocity of Bcr-Abl increases predicted response duration in PB (cutoff: 1.25?log/30 days) and BM (0.6). Bcr-Abl level and velocity of increase in BM as well as magnitude of increase in PB correlated with remaining periods of survival and predicted relapse within 2 months in nine of 10, 10 of 11 and four of four patients, respectively. Thus, these MRD parameters may guide timing and intensity of therapeutic modifications.Leukemia (2003) 17, 1700-1706. doi:10.1038/sj.leu.2403062
- Publication
Leukemia (08876924), 2003, Vol 17, Issue 9, p1700
- ISSN
0887-6924
- Publication type
Academic Journal
- DOI
10.1038/sj.leu.2403062