Contributions
Abstract: PB1659
Type: Publication Only
Background
Intensive chemotherapy allows to obtain complete remission (CR) rates ranging from 50 to 80% in adult patients with acute myelogenous leukemia (AML), but relapses still occur in 40–50% of cases. The cause of relapse is the persistence of tumor clones during therapy. The early response to the first course of chemotherapy is a marker of high chemosensitivity. It was shown by AMLCG that bone marrow blast level on day 14th of 1st chemotherapy cycle is predictive for remission rate, OS, RFS. RQ-PCR is much more sensitive than morphology for the identification and quantification of small blast populations in the bone marrow. The Wilms' tumor gene 1 (WT1), which is overexpressed in more than 90% of AML, is a useful marker for monitoring MRD. Quantification of WT1 transcript level in bone marrow (BM) at day 14 induction chemotherapy could more precisely discriminates patients at different risks of relapse than the number of blast cells.
Aims
To determine the clinical significance of WT1 overexpression level at the day 14th of the first chemotherapy cycle.
Methods
51 de novo AML pts median age 42,7 (range from 16 to 70) with overexpression WT1 were included in the study. «7+3» and «FLAG» were used for remission induction. Median of follow up was 18 mo. Bone marrow was aspirated prior to the start of chemotherapy and on the 14th day of induction treatment. WT1 expression was evaluated by the WT1 ProfileQuant (protocol EAC) kit (IPSOGEN) following the manufacturer’s instructions. A value more than 250 WT1/104 copies ABL was considered abnormal after being compared with samples from healthy donors.
Results
86,3 % (44/51) pts had AML remission. Median of WT1 level on the 14th day was 617copies/104 ABL (range from 3,7 to 19257,7). The remission rate did not depend on the achievement of normal expression of WT1 on day 14 (p = 0.11). However, there was a significant difference in values of WT1 at day 14 ± 3 in the patients with and without CR (740.0 vs. 4616.21 copies / 104 ABL, p = 0.0051). Pts with early (less than 6 mo) relapse had overexpression WT1 at day 14 (>250 WT1/104 copies ABL) (88,9% vs 0%, р = 0,001 Fisher exact test, two tailed, 100% sensitivity, 78% specificity). RFS and OS were more durable in pts with WT1 less than 250 copies (42,8mo vs 6,3mo, р=0,0003 and not reached median vs 10,4mo, р=0,009). There was a correlation between the normalization of WT1 at day 14 and the risk group (р = 0,019). Intermediate risk group was divided into two: the pts with overexpression WT1 had lower RFS 6,2 vs 10mo (р=0.026).
65,7% (23/35) the pts with <10% blasts on the 14th day had overexpression WT1. These pts had early (less than 6 mo) relapse: 84,6% (11/13) vs 0% (0/7) (р =0,002). The cut-off level of WT1 transcript level decrease to predict early relapse is 1.1 log.
In multivariate analysis including risk group, CR after the first induction course, blast percentage at day 14, level WT1 at 14 and 28 days, independent prognostic factors for RFS were level WT1 at day 14 and risk group (HR:8.66; 95% CI: 1,6-46.7; p=0.01 and HR:2.35; 95% CI: 1,0-5.3; p=0.04)
Conclusion
WT1 transcript level on day 14 of the first induction cycle is predictive for early relapse, RFS and OS. It is more sensitive that blast level. WT1 transcript level can discriminate intermediate prognosis pts into better and poorer prognosis
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Myeloid Leukemia, Prognostic factor, WT1
Abstract: PB1659
Type: Publication Only
Background
Intensive chemotherapy allows to obtain complete remission (CR) rates ranging from 50 to 80% in adult patients with acute myelogenous leukemia (AML), but relapses still occur in 40–50% of cases. The cause of relapse is the persistence of tumor clones during therapy. The early response to the first course of chemotherapy is a marker of high chemosensitivity. It was shown by AMLCG that bone marrow blast level on day 14th of 1st chemotherapy cycle is predictive for remission rate, OS, RFS. RQ-PCR is much more sensitive than morphology for the identification and quantification of small blast populations in the bone marrow. The Wilms' tumor gene 1 (WT1), which is overexpressed in more than 90% of AML, is a useful marker for monitoring MRD. Quantification of WT1 transcript level in bone marrow (BM) at day 14 induction chemotherapy could more precisely discriminates patients at different risks of relapse than the number of blast cells.
Aims
To determine the clinical significance of WT1 overexpression level at the day 14th of the first chemotherapy cycle.
Methods
51 de novo AML pts median age 42,7 (range from 16 to 70) with overexpression WT1 were included in the study. «7+3» and «FLAG» were used for remission induction. Median of follow up was 18 mo. Bone marrow was aspirated prior to the start of chemotherapy and on the 14th day of induction treatment. WT1 expression was evaluated by the WT1 ProfileQuant (protocol EAC) kit (IPSOGEN) following the manufacturer’s instructions. A value more than 250 WT1/104 copies ABL was considered abnormal after being compared with samples from healthy donors.
Results
86,3 % (44/51) pts had AML remission. Median of WT1 level on the 14th day was 617copies/104 ABL (range from 3,7 to 19257,7). The remission rate did not depend on the achievement of normal expression of WT1 on day 14 (p = 0.11). However, there was a significant difference in values of WT1 at day 14 ± 3 in the patients with and without CR (740.0 vs. 4616.21 copies / 104 ABL, p = 0.0051). Pts with early (less than 6 mo) relapse had overexpression WT1 at day 14 (>250 WT1/104 copies ABL) (88,9% vs 0%, р = 0,001 Fisher exact test, two tailed, 100% sensitivity, 78% specificity). RFS and OS were more durable in pts with WT1 less than 250 copies (42,8mo vs 6,3mo, р=0,0003 and not reached median vs 10,4mo, р=0,009). There was a correlation between the normalization of WT1 at day 14 and the risk group (р = 0,019). Intermediate risk group was divided into two: the pts with overexpression WT1 had lower RFS 6,2 vs 10mo (р=0.026).
65,7% (23/35) the pts with <10% blasts on the 14th day had overexpression WT1. These pts had early (less than 6 mo) relapse: 84,6% (11/13) vs 0% (0/7) (р =0,002). The cut-off level of WT1 transcript level decrease to predict early relapse is 1.1 log.
In multivariate analysis including risk group, CR after the first induction course, blast percentage at day 14, level WT1 at 14 and 28 days, independent prognostic factors for RFS were level WT1 at day 14 and risk group (HR:8.66; 95% CI: 1,6-46.7; p=0.01 and HR:2.35; 95% CI: 1,0-5.3; p=0.04)
Conclusion
WT1 transcript level on day 14 of the first induction cycle is predictive for early relapse, RFS and OS. It is more sensitive that blast level. WT1 transcript level can discriminate intermediate prognosis pts into better and poorer prognosis
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): Acute Myeloid Leukemia, Prognostic factor, WT1