Guadecitabine improved relapse-free survival in high-risk acute myeloid leukemia and myelodysplastic syndrome patients after transplant - phase II results from a single center

Sep 29, 2026

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This phase II, single-center clinical trial assessed guadecitabine, with or without donor lymphocyte infusion, after allogeneic stem cell transplantation in adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Three cohorts were defined by post-transplant disease status. Cohort 1 targeted morphological complete remission, Cohort 2 targeted MRD eradication within six cycles, and Cohort 3 received 12 cycles to improve relapse-free survival. Results showed meaningful remission and MRD clearance, with favorable safety and no unexpected events or graft failures.

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Abstract

Introduction

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ARTICLE-Acute Myeloid Leukemia Guadecitabine improved relapse-free survival in high-risk acute myeloid leukemia and myelodysplastic syndrome patients after transplant: phase II results from a single center Betül Oran,1 Peter Thall,2 Amin Alousi,1 Gheath Al-Atrash,1 Rohtesh Mehta,1 David Marin,1 Partow Kebriaei,1 Uday Popat,1 Roland Bassett,2 Qaiser Bashir,1 Jin Im,1 Amanda Olson,1 Jessica Jewell,1 Portia Smallbone,1 Elizabeth Shpall1 and Richard Champlin1 1 Department of Stem Cell Transplantation and Cellular Therapy and 2 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence: B. Oran [boran@mdanderson.org](boran@mdanderson.org) Received: February 17, 2025. Accepted: July 17, 2025. Early view: July 24, 2025. [https://doi.org/10.3324/haematol.2025.287628](https://doi.org/10.3324/haematol.2025.287628) ©2026 Ferrata Storti Foundation Published under a CC BY-NC license Abstract This phase II, single-center clinical trial evaluated the efficacy and safety of guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) . The study had three treatment cohorts based on post-transplant disease status. Cohort 1 included patients with hematologic relapse after transplant (N=13) . Cohort 2 consisted of patients with minimal residual disease (MRD) detected after transplant (N=18) . Cohort 3 compromised patients in remission without MRD within 100 days after transplant (N=24) . The primary objectives were achievement of morphological complete remission in cohort 1 and MRD eradication in cohort 2 within six cycles of guadecitabine. Cohort 3 patients received 12 cycles to improve relapse-free survival (RFS) . In cohort 1, 21.4% of patients achieved morphological complete remission. In cohort 2, 47.1% achieved MRD eradication. Those who cleared MRD had a 2-year RFS of 62.5% . Cohort 3 patients had a 2-year RFS rate of 62.5% with a median follow-up of 48 months. No unexpected adverse events occurred and no graft failures were observed. Guadecitabine demonstrated efficacy and a favorable safety profile across all cohorts, supporting the investigations of hypomethylating agents. Introduction The hypomethylating agents (HMA) azacitidine and decitabine are widely used in clinical practice as maintenance therapy to prevent relapse or as salvage regimens to treat disease recurrence following allogeneic stem cell transplant (allo-SCT) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) . Most data on the use of HMA in the post-transplant setting primarily come from phase II studies, which have demonstrated encouraging efficacy and a tolerable safety profile 1,2 However, two randomized clinical trials investigating HMA for post-transplant maintenance reported conflicting results3,4 raising questions about the of HMA effectiveness in improving relapse-free survival (RFS) . The use of HMA also has been explored in “pre-emptive”and “salvage” settings for AML and MDS patients following allo-SCT. In the “pre-emptive” setting, HMA are administered when post-transplant findings indicate a high risk of imminent hematologic relapse. For instance, Platzbekerand colleagues demonstrated that initiating azacitidine upon detection of minimal residual disease (MRD) delayed morphological relapse by approximately 8 months.5 Additional studies have supported the efficacy of HMA, with or without donor lymphocyte infusion (DLI), in treating MRDor overt relapse after a transplant.6-8 In the “salvage” setting, combining HMA with DLI has proven both safe and effective. Schoereder et al. reported an overall response rate of 30% in patients with relapsed AMLor MDS following allo-SCT using this combination therapy.9 Notably, the incidence and severity of graft-versus-host disease (GvHD) associated with HMA use have been low, even

FAQs

What trial population and treatment setting were studied?

Adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) were treated with guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation in a single-center phase II study.

How were the treatment cohorts defined and what were the primary objectives?

Cohort 1 included patients with hematologic relapse after transplant and aimed for morphological complete remission; Cohort 2 included patients with minimal residual disease (MRD) and aimed for MRD eradication within six cycles; Cohort 3 included patients in remission without MRD within 100 days and focused on improving relapse-free survival using 12 cycles.

What efficacy and safety outcomes were reported?

In Cohort 1, 21.4% achieved morphological complete remission, and in Cohort 2, 47.1% achieved MRD eradication; patients who cleared MRD had a 2-year relapse-free survival of 62.5%. No unexpected adverse events were reported and no graft failures were observed.

Sep 29, 2026

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