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471 Mega-Dose Decitabine Intensified Regimen Is More Effective at Eliminating Pre-HSCT Measurable Residual Disease Compared to the Bu/Cy Regimen: A Multicenter Prospective Phase II Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Novel Conditioning Regimens for Myeloid Malignancies
Hematology Disease Topics & Pathways:
Combination therapy, Therapies, Minimal Residual Disease
Sunday, December 10, 2023: 10:00 AM

Hao Zheng1*, Meng Lv, MD, PhD1, Chenhua Yan, MD2*, Jing Liu, MD3*, Yuanyuan Zhang, MD4*, Xiao-Dong Mo, MD1*, Yuqian Sun, MD5*, Yu Wang, MD3*, Xiaohui Zhang5*, Lanping Xu, MD1* and Xiao-Jun Huang, MD6

1Peking University People's Hospital, Beijing, China
2Peking University People's Hosital, Beijing, China
3Peking University People’s Hospital, Beijing, China
4Peking University People’s hospital, Beijing, China
5Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China
6Peking University People’s Hospital, Peking University Institute of Hematology, Beijing, China


Acute myeloid leukemia (AML) patients with high-risk pre-HSCT measurable residual disease (MRD, KMT2A-r, etc.) have a high relapse rate (>50%) even after allogeneic hematopoietic stem cell transplantation(allo-HSCT). In 2018, we developed two multi-institutional, single-arm, prospective phase II trials, to investigate the efficacy and safety of a novel intensified conditioning with “Mega-Dose 400mg/m2” decitabine following allo-HSCT for high-risk MRD AML (NCT03793517).


Inclusion: 1) Detectable pre-HSCT MRD detected by recurrent genetic abnormalities (KMT2A-r, DEK, etc.) in ELN adverse-risk AML; or high-level pre-HSCT MRD in all risk groups, defined as the reduction of recurrent genetic abnormalities 1 log compared to initial diagnosis (RUNX1:RUNX1T1, etc.); 2) Age18; no HSCT history, available donor; ECOG 0-2, HCT-CI 0-3. Uniform conditioning regimen: intravenous decitabine (200mg/m2/day) on days-12, -11, intravenous cytarabine+ busulfan+ cyclophosphamide (Bu/Cy) on days -10 to -2 (Blood. 2015;125(25):3956-62). The primary endpoint was cumulative incidence of relapse (CIR). Competing risk analysis and time-dependent Cox model were constructed in R software 4.21. Contemporary MRD+ AML patients with the same recurrent genetic abnormalities following Bu/Cy regimen or relapsed/refractory AML patients following 400mg/m2 decitabine regimen (NCT03799224) were enrolled as nest-control to compare the post-HSCT kinetics of recurrent genetic abnormalities.

Results: Between Dec 2018-Feb 2023, twenty-one patients received allo-HSCT from HLA-matched siblings (n=2), and haploidentical donors (n=19), including 13 patients with KMT2A-r genes. Median follow-up was 19 (4.6-58) months after HSCT. The cumulative 30-day neutrophil (median 13 days) was 100.0% and 100-day platelet engraftment and 95.2% (median 21 days); all patients reached negative MRD by flow cytometry after HSCT. This conditioning regimen was well tolerated without irreversible grade III-IV toxicity peri-engraftment.

Primary endpoint: 2-year CIR was 5.6% (95%CI: 0.3-23.3). Secondary endpoint: 2-year NRM was 4.8% (0.3-20.2); 2-year LFS was 89.6% (77-100); 2-year OS was 89.3% (76.2-100). The median fold reductions (log10) of leukemia burden with recurrent genetic abnormalities were 3.6 (range 1.3-5.1) one month after HSCT (Figure).

Conclusion: Compared to Bu/Cy regimen, "Mega-Dose” decitabine (400mg/m2) is a novel conditioning regimen with improved efficacy to eradicate pre-HSCT MRD and reduce post-HSCT relapse.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH