Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapy.
The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0.800 and P = 0.964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2.9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect.
Yanada
Masamitsu
M
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. myanada@mte.biglobe.ne.jp
Sugiura
Isamu
I
Takeuchi
Jin
J
Akiyama
Hideki
H
Maruta
Atsuo
A
Ueda
Yasunori
Y
Usui
Noriko
N
Yagasaki
Fumiharu
F
Yujiri
Toshiaki
T
Takeuchi
Makoto
M
Nishii
Kazuhiro
K
Kimura
Yukihiko
Y
Miyawaki
Shuichi
S
Narimatsu
Hiroto
H
Miyazaki
Yasushi
Y
Ohtake
Shigeki
S
Jinnai
Itsuro
I
Matsuo
Keitaro
K
Naoe
Tomoki
T
Ohno
Ryuzo
R
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis* / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010879:Piperazines / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl