Wilm’s Tumor 1 -Guided Preemptive Treatment with Hypomethylating Agents for Molecular Relapse of AML and MDS after Allogeneic Transplantation
Bone Marrow Transplantation(2020)
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.
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Key words
Myelodysplastic syndrome,Stem-cell research,Medicine/Public Health,general,Internal Medicine,Cell Biology,Public Health,Hematology,Stem Cells
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