Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia.
We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.
Department of Hematology, Catholic BMT Center, Research Institute of Molecular Genetics, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea. leeseok@catholic.ac.kr
S
S
Lee
D-W
DW
Kim
B-S
BS
Cho
J-H
JH
Yoon
S-H
SH
Shin
S-A
SA
Yahng
S-E
SE
Lee
K-S
KS
Eom
Y-J
YJ
Kim
N-G
NG
Chung
H-J
HJ
Kim
C-K
CK
Min
J-W
JW
Lee
W-S
WS
Min
C-W
CW
Park
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate