12th Congress of the European Hematology ... - Haematologica

One hundred eleven CN AML patients, considered at high risk according
to initial clinical presentation (WBC >30×10 9 /L, PGP MFI >6, secondary
AML) or on the basis of poor response to induction therapy,
were considered candidate to allogeneic HSCT. Fifty-one (46%) identified
an HLA identical donor and underwent transplantation, while
60 patients without a donor received chemotherapy-based intensification.
The two cohorts were comparable for WBC count and secondary
AML, while the transplanted patients were younger (45 vs 60
years) and with a lower incidence of PGP-positive (27% vs 47%) and
primary resistant (22% vs 42%) cases. HSCT was performed at a
median of 7 months (range: 1-99) from diagnosis. Twenty-eight
patients (55%) had a sibling donor, 23 an unrelated one. HSC source
was bone marrow in 30 cases, peripheral blood in 21. Twenty-eight
transplants were performed in first (n=23) or subsequent (n=5) remission.
Conditioning regimen was myeloablative in 40 cases (78%), nonmyeloablative
in 11. Results. Acute GvHD developed in 17 patients
(33%), mostly in MUD recipients. Chronic GvHD occurred in 14 of
41 evaluable patients (34%). One year transplant related mortality
(TRM) was 22% (11 cases). CR rate at engraftment was 90%. Sixteen
of 21 patients transplanted with active disease obtained CR (76%).
Relapse occurred in 17 patients, with no difference according to PGP
status at diagnosis. Disease-free survival (DFS) and OS was influenced
only by disease status at transplantation (p=0.027). Allogeneic SCT
conferred a significant advantage in survival. Median OS was 37
months in the transplanted patients, 12 months in the non-transplanted
ones (p=0.007). The advantage of transplantation was evident both
in the PGP+ and in the PGP- cases. Only HSCT was able to overcome
the negative impact of PGP, with an identical OS in PGP-positive and
PGP-negative transplanted patients. Summary. Allogeneic HSCT is an
effective therapy in CN AML, especially in cases with high risk, such
as over-expression of PGP. Transplant overcomes the impact of PGP
on survival and may be therefore pursued in patients who display this
high risk feature at diagnosis.
0460
LONGITUDINAL FOLLOW-UP OF WT1 GENE EXPRESSION AS MONITORING OF MINIMAL
RESIDUAL DISEASE IN ACUTE MYELOID LEUKEMIA FOLLOWING ALLOGENEIC BONE
MARROW TRANSPLANT
A. Candoni, 1 E. Toffoletti, 2 A. Chiarvesio, 2 A. Michelutti, 2
M. Cavallin, 2 D. Damiani, 2 R. Fanin2 1 Hematology Unit, UDINE; 2 Division of Hematology, UDINE, Italy
Introduction. WT1 is identified as a tumor suppressor gene encoding
a transcriptional regulator and playing a role in the development of
Wilms Tumor. WT1 overexpression is described in several oncological
diseases including leukemias. The majority of acute myeloid
leukemia (AML) patients don't have a suitable specific molecular
marker for monitoring minimal residual disease (MRD). Quantification
of WT1 in bone marrow samples can be useful as a marker of
MRD and can predict the relapse of AML. Methods and Results. Here
we present the preliminary results of our study in which we are evaluating
the dynamic expression of WT-1 in AML patients (pts) following
Allogeneic bone marrow transplantation (BMT). The expression
of WT-1 was measured using Real Time Quantitative RT-PCR with
the specific TaqMan probe; the WT-1 expression was related to
expression of the control gene ABL. The cDNA level of WT-1 was
detected in bone marrow samples from 20 AML pts at diagnosis (11
males and 9 females), at the time of transplant and after the allogeneic
BMT. Samples of diagnosis showed high WT1 expression levels in
all cases with a mean of 5468 (SD 4025) copies of WT1/10000 Abl,
median 4200 (range 658-13923) copies WT1/10000 Abl. At transplant
12 pts (60%) were in complete cytologic remission (CcR) and 8 (40%)
had refractory or relapsed AML. Bone marrow samples from pts in
CcR at BMT showed significantly lower WT1 expression levels (mean
74,3±126), compared to the samples from pts with relapsed or refractory
disease (mean 5627±4165) (p