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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-06-1831.
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1698-1704
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
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
From the Department of Molecular Medicine, Osaka
University Graduate School of Medicine, Japan; Department
of Clinical Laboratory Science, Osaka University Medical School,
Japan; and Department of Medicine, Osaka Minami National
Hospital, Osaka, Japan.
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 acute myeloid
leukemia, acute lymphoid leukemia, and chronic myeloid leukemia
(accelerated phase or blast crisis) 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 significantly decreased
compared with the level in healthy volunteers. The probability of
relapse occurring within 40 days significantly increased step-by-step
according to the increase in WT1 expression level (100%
for 1.0 × 10 2-5.0 × 10 2, 44.4% for 4.0 × 10 3-1.0 × 10 2, 10.2% for
4.0 × 10 4-4.0 × 10 3, and 0.8% for < 4.0 × 10 4) when WT1 level in K562 was defined
as 1.0). WT1 levels in patients having relapse increased
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 < .05). No patients with a short doubling
time of WT1 transcripts (< 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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