POST-TRANSPLANTATION MONITORING OF ACUTE MYELOID LEUKEMIA BY SERIAL MEASUREMENT OF WT1 GENE EXPRESSION LEVELS.
(Abstract release date: 05/19/16)
EHA Library. Gudozhnikova Y. 06/09/16; 134558; PB1658
Dr. Yana Gudozhnikova
Contributions
Contributions
Abstract
Abstract: PB1658
Type: Publication Only
Background
The major problem in the treatment of acute myeloid leukemia (AML) with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the relapse of the underlying disease, poorly responsive to chemotherapy. For its early detection, molecular monitoring methods were introduced, of which serial measurement of Wilms Tumor-1 (WT1) gene expression levels is considered to be the most efficient (Candoni et al., 2011; Zhao et al., 2011; Mamaev et al., 2015).
Aims
We aimed to estimate the molecular monitoring potential for early detection of relapse and the quality of its treatment in AML patients after allo-HSCT.
Methods
A serial measurement of WT1 gene expression levels by quantitative real-time polymerase chain reaction (PCR) was conducted in 65 AML patients in the post-transplant period. The threshold for identification of WT1 gene overexpression was above 250 x 104 copies of the ABL gene. The clinical and laboratory characteristics of AML patients after allo-HSCT are presented in Table 1:
Results
The maximum initial level of WT1 gene expression ranged from 259 to 56884 copies/104 copies of ABL gene (9869 copies on average). Its expression hardly depended on the cytological type of AML or the cytogenetic type of the cells. According to the obtained data on WT gene expression, two groups of patients were formed. The first group consisted of 28 patients with stable normal WT1 gene expression during the post-transplantation period; the second group consisted of 37 patients with impaired WT1 gene expression. In the period after transplantation WT1 gene expression levels were consistent with or surpassing those of specific markers of minimal residual disease in parallel analysis. Our data showed that in one-third of the patients WT1 overexpression preceded the increase in blast cells in the bone marrow, thus predicting a relapse. For post-transplantation relapse therapy hypomethylating agents in combination with or without donor lymphocyte infusion were applied in 31 patients. The therapy results were not encouraging. In 22 patients mortality was due to the relapse of the underlying disease. Complete remission was only achieved in 6 patients with AML. Three of them later died from GVHD, acute heart failure and sepsis on D+101, D+541 and D+350 after allo-HSCT respectively.
Conclusion
Molecular monitoring of acute myeloid leukemia after allo-HSCT using serial measurement of WT1 gene expression levels allows to reveal cytological relapses at an earlier stage and may soon be used to assess the treatment of prognostically adverse post-transplant relapses of AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Allo BMT, WT1
Type: Publication Only
Background
The major problem in the treatment of acute myeloid leukemia (AML) with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the relapse of the underlying disease, poorly responsive to chemotherapy. For its early detection, molecular monitoring methods were introduced, of which serial measurement of Wilms Tumor-1 (WT1) gene expression levels is considered to be the most efficient (Candoni et al., 2011; Zhao et al., 2011; Mamaev et al., 2015).
Aims
We aimed to estimate the molecular monitoring potential for early detection of relapse and the quality of its treatment in AML patients after allo-HSCT.
Methods
A serial measurement of WT1 gene expression levels by quantitative real-time polymerase chain reaction (PCR) was conducted in 65 AML patients in the post-transplant period. The threshold for identification of WT1 gene overexpression was above 250 x 104 copies of the ABL gene. The clinical and laboratory characteristics of AML patients after allo-HSCT are presented in Table 1:
| Number of patients | 65 |
| AML | |
| AML de novo | 51 (М0-4, М1-6, М2-12, М3-1, М4-20, М5-6, М6-1, М7-1) |
| Secondary AML | 14 |
| Patient sex, nMale 36Female 29 | |
| Age at HSCT ( mediana) 26 (4-56) | |
| Cytogenetics, n Favorable 0 Intermediate 50 Infavorable 15 | |
| Molecular markers, n Yes 16No 49 | |
| HSC source, n | |
| Bone marrow 34Peripheral blood 31 | |
| Conditioning regimen, n | |
| MA 44Non-MA 21 | |
| Donor type, nHLA-id sibling 12Matched unrelated 41Haploidentical 12 | |
| Number of transplanted CD34+ cells (mediana) | 4,78*106 (2,2-11,9) |
Results
The maximum initial level of WT1 gene expression ranged from 259 to 56884 copies/104 copies of ABL gene (9869 copies on average). Its expression hardly depended on the cytological type of AML or the cytogenetic type of the cells. According to the obtained data on WT gene expression, two groups of patients were formed. The first group consisted of 28 patients with stable normal WT1 gene expression during the post-transplantation period; the second group consisted of 37 patients with impaired WT1 gene expression. In the period after transplantation WT1 gene expression levels were consistent with or surpassing those of specific markers of minimal residual disease in parallel analysis. Our data showed that in one-third of the patients WT1 overexpression preceded the increase in blast cells in the bone marrow, thus predicting a relapse. For post-transplantation relapse therapy hypomethylating agents in combination with or without donor lymphocyte infusion were applied in 31 patients. The therapy results were not encouraging. In 22 patients mortality was due to the relapse of the underlying disease. Complete remission was only achieved in 6 patients with AML. Three of them later died from GVHD, acute heart failure and sepsis on D+101, D+541 and D+350 after allo-HSCT respectively.
Conclusion
Molecular monitoring of acute myeloid leukemia after allo-HSCT using serial measurement of WT1 gene expression levels allows to reveal cytological relapses at an earlier stage and may soon be used to assess the treatment of prognostically adverse post-transplant relapses of AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Allo BMT, WT1
Abstract: PB1658
Type: Publication Only
Background
The major problem in the treatment of acute myeloid leukemia (AML) with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the relapse of the underlying disease, poorly responsive to chemotherapy. For its early detection, molecular monitoring methods were introduced, of which serial measurement of Wilms Tumor-1 (WT1) gene expression levels is considered to be the most efficient (Candoni et al., 2011; Zhao et al., 2011; Mamaev et al., 2015).
Aims
We aimed to estimate the molecular monitoring potential for early detection of relapse and the quality of its treatment in AML patients after allo-HSCT.
Methods
A serial measurement of WT1 gene expression levels by quantitative real-time polymerase chain reaction (PCR) was conducted in 65 AML patients in the post-transplant period. The threshold for identification of WT1 gene overexpression was above 250 x 104 copies of the ABL gene. The clinical and laboratory characteristics of AML patients after allo-HSCT are presented in Table 1:
Results
The maximum initial level of WT1 gene expression ranged from 259 to 56884 copies/104 copies of ABL gene (9869 copies on average). Its expression hardly depended on the cytological type of AML or the cytogenetic type of the cells. According to the obtained data on WT gene expression, two groups of patients were formed. The first group consisted of 28 patients with stable normal WT1 gene expression during the post-transplantation period; the second group consisted of 37 patients with impaired WT1 gene expression. In the period after transplantation WT1 gene expression levels were consistent with or surpassing those of specific markers of minimal residual disease in parallel analysis. Our data showed that in one-third of the patients WT1 overexpression preceded the increase in blast cells in the bone marrow, thus predicting a relapse. For post-transplantation relapse therapy hypomethylating agents in combination with or without donor lymphocyte infusion were applied in 31 patients. The therapy results were not encouraging. In 22 patients mortality was due to the relapse of the underlying disease. Complete remission was only achieved in 6 patients with AML. Three of them later died from GVHD, acute heart failure and sepsis on D+101, D+541 and D+350 after allo-HSCT respectively.
Conclusion
Molecular monitoring of acute myeloid leukemia after allo-HSCT using serial measurement of WT1 gene expression levels allows to reveal cytological relapses at an earlier stage and may soon be used to assess the treatment of prognostically adverse post-transplant relapses of AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Allo BMT, WT1
Type: Publication Only
Background
The major problem in the treatment of acute myeloid leukemia (AML) with allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the relapse of the underlying disease, poorly responsive to chemotherapy. For its early detection, molecular monitoring methods were introduced, of which serial measurement of Wilms Tumor-1 (WT1) gene expression levels is considered to be the most efficient (Candoni et al., 2011; Zhao et al., 2011; Mamaev et al., 2015).
Aims
We aimed to estimate the molecular monitoring potential for early detection of relapse and the quality of its treatment in AML patients after allo-HSCT.
Methods
A serial measurement of WT1 gene expression levels by quantitative real-time polymerase chain reaction (PCR) was conducted in 65 AML patients in the post-transplant period. The threshold for identification of WT1 gene overexpression was above 250 x 104 copies of the ABL gene. The clinical and laboratory characteristics of AML patients after allo-HSCT are presented in Table 1:
| Number of patients | 65 |
| AML | |
| AML de novo | 51 (М0-4, М1-6, М2-12, М3-1, М4-20, М5-6, М6-1, М7-1) |
| Secondary AML | 14 |
| Patient sex, nMale 36Female 29 | |
| Age at HSCT ( mediana) 26 (4-56) | |
| Cytogenetics, n Favorable 0 Intermediate 50 Infavorable 15 | |
| Molecular markers, n Yes 16No 49 | |
| HSC source, n | |
| Bone marrow 34Peripheral blood 31 | |
| Conditioning regimen, n | |
| MA 44Non-MA 21 | |
| Donor type, nHLA-id sibling 12Matched unrelated 41Haploidentical 12 | |
| Number of transplanted CD34+ cells (mediana) | 4,78*106 (2,2-11,9) |
Results
The maximum initial level of WT1 gene expression ranged from 259 to 56884 copies/104 copies of ABL gene (9869 copies on average). Its expression hardly depended on the cytological type of AML or the cytogenetic type of the cells. According to the obtained data on WT gene expression, two groups of patients were formed. The first group consisted of 28 patients with stable normal WT1 gene expression during the post-transplantation period; the second group consisted of 37 patients with impaired WT1 gene expression. In the period after transplantation WT1 gene expression levels were consistent with or surpassing those of specific markers of minimal residual disease in parallel analysis. Our data showed that in one-third of the patients WT1 overexpression preceded the increase in blast cells in the bone marrow, thus predicting a relapse. For post-transplantation relapse therapy hypomethylating agents in combination with or without donor lymphocyte infusion were applied in 31 patients. The therapy results were not encouraging. In 22 patients mortality was due to the relapse of the underlying disease. Complete remission was only achieved in 6 patients with AML. Three of them later died from GVHD, acute heart failure and sepsis on D+101, D+541 and D+350 after allo-HSCT respectively.
Conclusion
Molecular monitoring of acute myeloid leukemia after allo-HSCT using serial measurement of WT1 gene expression levels allows to reveal cytological relapses at an earlier stage and may soon be used to assess the treatment of prognostically adverse post-transplant relapses of AML.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Allo BMT, WT1
{{ help_message }}
{{filter}}