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1.
Eur J Haematol ; 107(2): 283-292, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33987857

ABSTRACT

OBJECTIVE: As peripheral blood (PB) Wilm's Tumor 1 (WT1)-mRNA expression is established as MRD-marker during conventional AML chemotherapy, impact of pretransplant WT1 expression remains unclear. Therefore, we aimed to assess prognostic impact of pretransplant WT1 expression on post-transplant outcome in patients with AML/MDS. METHODS: In 64 AML/MDS patients, pretransplant WT1 expression was retrospectively analyzed using a standardized assay offering high sensitivity, specificity, and a validated cut-off. Patients were divided into three groups determined by pretransplant remission and WT1 expression. Post-transplant outcome of these groups was compared regarding cumulative incidence of relapse (CIR), relapse-free (RFS), and overall survival (OS). RESULTS: Pretransplant forty-six patients (72%) showed hematologic remission, including 21 (46%) MRD-negative and 25 (54%) MRD-positive patients indicated by WT1 expression, while 18 refractory patients (28%) showed active disease. Two-year estimates of post-transplant CIR, RFS, and OS were similar in MRD-positive (61%, 37%, 54%) and refractory patients (70%, 26%, 56%), but significantly inferior compared with MRD-negative patients (10%, 89%, 90%). After multivariable adjustment, pretransplant MRD negativity measured by WT1 expression retained its prognostic impact on CIR (P = .008), RFS (P = .005), and OS (P = .049). CONCLUSIONS: PB WT1 expression represents a useful method to estimate pretransplant MRD, which is highly predictable for post-transplant outcome and may help improving peri-transplant management in AML/MDS patients.


Subject(s)
Biomarkers, Tumor , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/mortality , Neoplasm, Residual/genetics , WT1 Proteins/genetics , Adult , Aged , Blood Cells , Cell-Free Nucleic Acids , Female , Gene Expression , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Myelodysplastic Syndromes/pathology , Myelodysplastic Syndromes/therapy , Neoplasm, Residual/diagnosis , Preoperative Period , Prognosis , RNA, Messenger , Recurrence , Retrospective Studies , Transplantation, Homologous , Treatment Outcome , Young Adult
2.
Bone Marrow Transplant ; 56(2): 442-450, 2021 02.
Article in English | MEDLINE | ID: mdl-32873914

ABSTRACT

Hypomethylating agents (HMA) for relapsed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic transplantation (allo-SCT) are most effective when used at the stage of molecular relapse. As Wilm's Tumor 1 (WT1)- expression has proven to serve as broadly applicable, sensitive and specific minimal residual disease (MRD) marker, we measured WT1-expression in 35 AML and MDS patients using a standardized assay for the guidance of therapy with HMA and donor lymphocyte infusions (DLI). Molecular relapse was detected in median 168 days post-transplant prompting therapy with a median of six HMA cycles and at least one DLI (n = 22, 63%). Hereby, 13 patients (37%) achieved major response (=MRD- complete remission [CR]), and 7 patients (20%) achieved minor response (=MRD+ CR), whereas 15 patients (43%) progressed into hematologic relapse. Two-year overall survival (OS) rate was 35% including 11 patients (31%) with ongoing MRD- remission for a median of 21 months. Patients with the major response after six cycles had significantly better OS suggesting that those not achieving MRD negativity after six cycles are candidates for alternative therapies. Combining MRD-monitoring of WT1-expression and preemptive therapy with HMA and DLI appears as a practicable and efficient approach for imminent relapse after allo-SCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Kidney Neoplasms , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Neoplasm, Residual , Recurrence , Transplantation, Homologous , WT1 Proteins
3.
Blood Cancer J ; 9(11): 86, 2019 11 12.
Article in English | MEDLINE | ID: mdl-31719523

ABSTRACT

Few reports suggested a prognostic impact of Wilms'Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Overall, 54 patients (57%) showed WT1-mRNA overexpression, while 40 patients (43%) had normal WT1-mRNA expression. This enabled discrimination between MDS and both healthy controls and non-MDS cytopenias. Furthermore, WT1-mRNA expression correlated with WHO 2016 subcategories and IPSS-R as indicated by mean WT1-mRNA expression and frequency of WT1-mRNA overexpressing patients within respective subgroups. Regarding the entire group, PB WT1-mRNA expression was associated with prognosis, as those patients showing WT1-mRNA overexpression had higher risk for disease progression and AML transformation and accordingly shorter progression-free, leukemia-free and overall survival in univariate analysis. In multivariate analysis, prognostic impact of PB WT1-mRNA expression status was independent of IPSS-R and enabled more precise prediction of PFS, but not OS, within IPSS-R very low/low and intermediate risk groups. Overall, measuring PB WT1-mRNA appears valuable to support diagnostics and refine prognostication provided by the IPSS-R.


Subject(s)
Gene Expression Regulation , Myelodysplastic Syndromes , RNA, Messenger/blood , WT1 Proteins/blood , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Middle Aged , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/mortality , Survival Rate
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