Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia
Aim. To demonstrate diagnostic and prognostic significance of series measurement of WT1 expression in patients with acute myeloid leukemia (AML) after allogenic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. The clinical trial included 88 AML patients (38 females (4...
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Practical Medicine Publishing House
2018-07-01
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| Series: | Клиническая онкогематология |
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| Online Access: | http://bloodjournal.ru/wp-content/uploads/2018/06/5.pdf |
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| author | YaV Gudozhnikova NN Mamaev IM Barkhatov VA Katerina TL Gindina AI Shakirova SN Bondarenko OA Slesarchuk EI Darskaya OV Paina LS Zubarovskaya BV Afanas’ev |
| author_facet | YaV Gudozhnikova NN Mamaev IM Barkhatov VA Katerina TL Gindina AI Shakirova SN Bondarenko OA Slesarchuk EI Darskaya OV Paina LS Zubarovskaya BV Afanas’ev |
| author_sort | YaV Gudozhnikova |
| collection | DOAJ |
| description | Aim. To demonstrate diagnostic and prognostic significance of series measurement of WT1 expression in patients with acute myeloid leukemia (AML) after allogenic hematopoietic stem cell transplantation (allo-HSCT).
Materials & Methods. The clinical trial included 88 AML patients (38 females (43 %) and 50 males (57 %) aged 2–68, median 30 years). All the patients received allo-HSCT. Bone marrow was aspirated before (D0) and after HSCT (D+30, D+60, and D+100).
Results. The univariate analysis showed statistically significant differences in 2-year overall survival with respect to the following factors: with and without remission at the moment of HSCT (p < 0.001), with and without chronic graft vs. host disease (cGVHD) (p = 0.002), primary or secondary (MDS) AML (p = 0,028), WT1 gene expression < and > 250 copies before HSCT (p < 0.001) and at time points D+60 (p = 0.012), and D+100 (p < 0.001). Multivariate analysis revealed similar statistical significance of differences among patients transplanted in remission (p = 0.041) and with cGVHD (p = 0.03). In univariate analysis statistically significant differences in 2-year event-free survival (EFS) were found: a) in patients with allo-HSCT, either in remission or not (p < 0.001); b) using HSC, but not bone marrow, as transplant source (p < 0.026); c) with normal or high WT1 expression at the stage of HSCT (p < 0.001) and at time point D+100 (p < 0.001); d) using HSC from related or unrelated donor (p = 0.006); e) in patients with cGVHD (p = 0.05). In multivariate analysis independent positive effect on EFS was observed only in patients with normal WT1 expression at D+100 (p = 0.011) and with cGVHD (p = 0.038). Cumulative incidence of posttransplant relapse (PTR) in AML patients with normal or high WT1 expression at the stage of HSCT within the 2-year follow-up was significantly different (28.2 vs. 58.9 %; p = 0.002), also in measurements of this parameter at D+60 and D+100 (p = 0.015 and p < 0.001, respectively). In 1/4 of patients cytological relapses (cPTR) appeared considerably later than molecular relapses (mPTR), i.e. 13–489 days later (median 35 days), which is accounted for by early preventive therapy aimed at cPTR prophylaxis against the background of already recorded mPTR. According to our data, GVHD plays a crucial role in cPTR management.
Conclusion. Phenomenon of WT1 expression normalization after allo-HSCT in AML patients proves to have a high diagnostic and prognostic significance. Introduction of this approach into clinical practice seems highly advisable for national oncohematological centers. |
| format | Article |
| id | doaj-art-109fdb727948463c8a7259557bc69cd9 |
| institution | OA Journals |
| issn | 1997-6933 2500-2139 |
| language | Russian |
| publishDate | 2018-07-01 |
| publisher | Practical Medicine Publishing House |
| record_format | Article |
| series | Клиническая онкогематология |
| spelling | doaj-art-109fdb727948463c8a7259557bc69cd92025-08-20T01:58:56ZrusPractical Medicine Publishing HouseКлиническая онкогематология1997-69332500-21392018-07-0111324125110.21320/2500-2139-2018-11-3-241-251Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid LeukemiaYaV Gudozhnikova0NN Mamaev1IM Barkhatov2VA Katerina3TL Gindina4AI Shakirova5SN Bondarenko6OA Slesarchuk7EI Darskaya8OV Paina9LS Zubarovskaya10BV Afanas’ev11RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022Aim. To demonstrate diagnostic and prognostic significance of series measurement of WT1 expression in patients with acute myeloid leukemia (AML) after allogenic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. The clinical trial included 88 AML patients (38 females (43 %) and 50 males (57 %) aged 2–68, median 30 years). All the patients received allo-HSCT. Bone marrow was aspirated before (D0) and after HSCT (D+30, D+60, and D+100). Results. The univariate analysis showed statistically significant differences in 2-year overall survival with respect to the following factors: with and without remission at the moment of HSCT (p < 0.001), with and without chronic graft vs. host disease (cGVHD) (p = 0.002), primary or secondary (MDS) AML (p = 0,028), WT1 gene expression < and > 250 copies before HSCT (p < 0.001) and at time points D+60 (p = 0.012), and D+100 (p < 0.001). Multivariate analysis revealed similar statistical significance of differences among patients transplanted in remission (p = 0.041) and with cGVHD (p = 0.03). In univariate analysis statistically significant differences in 2-year event-free survival (EFS) were found: a) in patients with allo-HSCT, either in remission or not (p < 0.001); b) using HSC, but not bone marrow, as transplant source (p < 0.026); c) with normal or high WT1 expression at the stage of HSCT (p < 0.001) and at time point D+100 (p < 0.001); d) using HSC from related or unrelated donor (p = 0.006); e) in patients with cGVHD (p = 0.05). In multivariate analysis independent positive effect on EFS was observed only in patients with normal WT1 expression at D+100 (p = 0.011) and with cGVHD (p = 0.038). Cumulative incidence of posttransplant relapse (PTR) in AML patients with normal or high WT1 expression at the stage of HSCT within the 2-year follow-up was significantly different (28.2 vs. 58.9 %; p = 0.002), also in measurements of this parameter at D+60 and D+100 (p = 0.015 and p < 0.001, respectively). In 1/4 of patients cytological relapses (cPTR) appeared considerably later than molecular relapses (mPTR), i.e. 13–489 days later (median 35 days), which is accounted for by early preventive therapy aimed at cPTR prophylaxis against the background of already recorded mPTR. According to our data, GVHD plays a crucial role in cPTR management. Conclusion. Phenomenon of WT1 expression normalization after allo-HSCT in AML patients proves to have a high diagnostic and prognostic significance. Introduction of this approach into clinical practice seems highly advisable for national oncohematological centers.http://bloodjournal.ru/wp-content/uploads/2018/06/5.pdfacute myeloid leukemiaallo-HSCTposttransplant relapsediagnostics and treatment with molecular monitoring of WT1 expressiongraft vs. host disease |
| spellingShingle | YaV Gudozhnikova NN Mamaev IM Barkhatov VA Katerina TL Gindina AI Shakirova SN Bondarenko OA Slesarchuk EI Darskaya OV Paina LS Zubarovskaya BV Afanas’ev Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia Клиническая онкогематология acute myeloid leukemia allo-HSCT posttransplant relapse diagnostics and treatment with molecular monitoring of WT1 expression graft vs. host disease |
| title | Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia |
| title_full | Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia |
| title_fullStr | Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia |
| title_full_unstemmed | Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia |
| title_short | Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia |
| title_sort | results of molecular monitoring in posttransplant period by means of series investigation of wt1 gene expression in patients with acute myeloid leukemia |
| topic | acute myeloid leukemia allo-HSCT posttransplant relapse diagnostics and treatment with molecular monitoring of WT1 expression graft vs. host disease |
| url | http://bloodjournal.ru/wp-content/uploads/2018/06/5.pdf |
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