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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-06-1831.
Submitted June 21, 2002
Accepted October 1, 2002
The usefulness of monitoring WT1 gene transcripts for the prediction and management of relapse following allogeneic stem cell transplantation in acute type leukemia
Hiroyasu Ogawa*, Hiroya Tamaki, Kazuhiro Ikegame, Toshihiro Soma, Manabu Kawakami, Akihiro Tsuboi, Eui Ho Kim, Naoki Hosen, Masaki Murakami, Tatsuya Fujioka, Tomoki Masuda, Yuki Taniguchi, Sumiyuki Nishida, Yusuke Oji, Yoshihiro Oka, and Haruo Sugiyama
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Medicine, Osaka Minami National Hospital, Osaka, Japan
Department of Clinical Laboratory Science, Osaka University Medical School, Osaka, Japan
* Corresponding author; email: ogachan{at}ceres.ocn.ne.jp.
In acute type leukemia, no method for the prediction of relapse following allogeneic stem cell transplantation based on minimal residual disease (MRD) levels is established yet. In the present study, MRD in 72 cases of allogeneic transplantation for AML, ALL, and CML (CP or BC) was monitored frequently by quantitating the transcript of WT1 gene, a "panleukemic MRD marker", using reverse transcriptase-polymerase chain reaction. Based on the negativity of expression of chimeric genes, the background level of WT1 transcripts in bone marrow following allogeneic transplantation was found to be significantly decreased compared with the level in normal volunteers. The probability of relapse occurring within 40 days was found to significantly increase step-by-step according to the increase in WT1 expression level (100% for 1.0x10-2 to 5.0x10-2, 44.4% for 4.0x10-3 to 1.0x10-2, 10.2% for 4.0x10-4 to 4.0x10-3 and 0.8% for <4.0x10-4, when WT1 level in K562 was defined as 1.0). WT1 levels in relapsed patients were found to increase exponentially with a constant doubling time. The doubling time of the WT1 level in patients for whom the discontinuation of immunosuppressive agents or donor leukocyte infusion was effective was significantly longer than that for patients in whom it was not (P<0.05). No patients with a short doubling time of WT1 transcripts (less than 13 days) responded to these immunomodulation therapies. These findings strongly suggest that the WT1 assay is very useful for the prediction and management of relapse following allogeneic stem cell transplantation regardless of the presence of chimeric gene markers.
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