title: Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
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.
authors.affiliation: Departments of Hematology/Oncology of University Hospitals Frankfurt, Hannover, Dresden, Münster, Ulm, Heidelberg, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wassmann
authors.forename: Heike
authors.initials: H
authors.lastname: Pfeifer
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhaüser
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
authors.forename: Urban J
authors.initials: UJ
authors.lastname: Scheuring
authors.forename: Patrick
authors.initials: P
authors.lastname: Brück
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: Nadezda
authors.initials: N
authors.lastname: Basara
authors.forename: Jolanta
authors.initials: J
authors.lastname: Perz
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Georg
authors.initials: G
authors.lastname: Ledderose
authors.forename: Rolf
authors.initials: R
authors.lastname: Mahlberg
authors.forename: Anja
authors.initials: A
authors.lastname: Binckebanck
authors.forename: Harald
authors.initials: H
authors.lastname: Gschaidmeier
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D016313:Genes, abl; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate