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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We thank the staff of the Transplantation Unit of the Department of Hematology, Oncology, and Clinical Immunology for excellent patient care.
Conflict of interest
CR received financial travel support from Celgene Deutschland GmbH. TS received financial travel support, lecture fees, research funding, and participated in advisory boards for Celgene GmbH. TS received financial travel support, lecture fees, and participated in advisory boards for Janssen-Cilag GmbH. A Rotorgene PCR cycler was provided free of charge by Qiagen (Hilden, Germany) for routine use in this study. No other financial or logistic support was provided by the company for this analysis.
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Rautenberg, C., Bergmann, A., Pechtel, S. et al. Wilm’s Tumor 1-guided preemptive treatment with hypomethylating agents for molecular relapse of AML and MDS after allogeneic transplantation. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01039-2