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

Authors
  • Wassmann, Barbara
  • Pfeifer, Heike
  • Stadler, Michael
  • Bornhaüser, Martin
  • Bug, Gesine
  • Scheuring, Urban J
  • Brück, Patrick
  • Stelljes, Matthias
  • Schwerdtfeger, Rainer
  • Basara, Nadezda
  • Perz, Jolanta
  • Bunjes, Donald
  • Ledderose, Georg
  • Mahlberg, Rolf
  • Binckebanck, Anja
  • Gschaidmeier, Harald
  • Hoelzer, Dieter
  • Ottmann, Oliver G
Type
Published Article
Journal
Blood
Publication Date
Jul 15, 2005
Volume
106
Issue
2
Pages
458–463
Identifiers
PMID: 15817679
Source
Medline
License
Unknown

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) ((early)CR(mol)). All patients who achieved an (early)CR(mol) 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 (early)CR(mol) 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.

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