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Prospective monitoring of BCR‐ABL1 transcript levels in patients with Philadelphia chromosome‐positive acute lymphoblastic leukaemia undergoing imatinib‐combined chemotherapy
Author(s) -
Yanada Masamitsu,
Sugiura Isamu,
Takeuchi Jin,
Akiyama Hideki,
Maruta Atsuo,
Ueda Yasunori,
Usui Noriko,
Yagasaki Fumiharu,
Yujiri Toshiaki,
Takeuchi Makoto,
Nishii Kazuhiro,
Kimura Yukihiko,
Miyawaki Shuichi,
Narimatsu Hiroto,
Miyazaki Yasushi,
Ohtake Shigeki,
Jinnai Itsuro,
Matsuo Keitaro,
Naoe Tomoki,
Ohno Ryuzo
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07377.x
Subject(s) - imatinib , medicine , chemotherapy , philadelphia chromosome , oncology , lymphoblastic leukemia , cancer research , leukemia , chromosomal translocation , gene , biology , genetics , myeloid leukemia
Summary 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.