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Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)

Barbara Wassmann, Heike Pfeifer, Michael Stadler, Martin Bornhaüser, Gesine Bug, Urban J. Scheuring, Patrick Brück, Matthias Stelljes, Rainer Schwerdtfeger, Nadezda Basara, Jolanta Perz, Donald Bunjes, Georg Ledderose, Rolf Mahlberg, Anja Binckebanck, Harald Gschaidmeier, Dieter Hoelzer and Oliver G. Ottmann

Abstract

In adult Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL), minimal residual disease (MRD) after stem cell transplantation (SCT) is associated with a relapse probability exceeding 90%. Starting imatinib in the setting of MRD may decrease this high relapse rate. In this prospective multicenter study, 27 Ph+ ALL patients received imatinib upon detection of MRD after SCT. Bcr-abl transcripts became undetectable in 14 (52%) of 27 patients, after a median of 1.5 months (0.9-3.7 months) (earlyCRmol). All patients who achieved an earlyCRmol remained in remission for the duration of imatinib treatment; 3 patients relapsed after imatinib was discontinued. Failure to achieve polymerase chain reaction (PCR) negativity shortly after starting imatinib predicted relapse, which occurred in 12 (92%) of 13 patients after a median of 3 months. Disease-free survival (DFS) in earlyCRmol patients is 91% ± 9% and 54% ± 21% after 12 and 24 months, respectively, compared with 8% ± 7% after 12 months in patients remaining MRD+ (P < .001). In conclusion, approximately half of patients with Ph+ ALL receiving imatinib for MRD positivity after SCT experience prolonged DFS, which can be anticipated by the rapid achievement of a molecular complete remission (CR). Continued detection of bcr-abl transcripts after 2 to 3 months on imatinib identifies patients who will ultimately experience relapse and in whom additional or alternative antileukemic treatment should be initiated.

  • Submitted May 13, 2004.
  • Accepted March 1, 2005.
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