Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
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.
Wassmann
Barbara
B
Departments of Hematology/Oncology of University Hospitals Frankfurt, Hannover, Dresden, Münster, Ulm, Heidelberg, Munich, Germany.
Pfeifer
Heike
H
Stadler
Michael
M
Bornhaüser
Martin
M
Bug
Gesine
G
Scheuring
Urban J
UJ
Brück
Patrick
P
Stelljes
Matthias
M
Schwerdtfeger
Rainer
R
Basara
Nadezda
N
Perz
Jolanta
J
Bunjes
Donald
D
Ledderose
Georg
G
Mahlberg
Rolf
R
Binckebanck
Anja
A
Gschaidmeier
Harald
H
Hoelzer
Dieter
D
Ottmann
Oliver G
OG
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
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate