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2107 Efficacy and Safety of Mitoxantrone Hydrochloride Liposome in Combination with Thiotepa-Busulfan-Fludarabine As an Intensive Conditioning Regimen Preceding Salvage Allogeneic Stem Cell Transplantation in Relapsed or Refractory Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Xiaoning Wang, PhD1, Juan Ren, M.D2*, Huachao Zhu, M.D3*, Yuqi Wang, M.D4* and Pengcheng He5*

1Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'An, China
2hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
3The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
4The First Affiliated Hospital of Xi'an Jiaotong University, Xi'An, China
5Department of Hematology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

Background:Patients with relapsed and refractory acute myeloid leukemia (R/R AML) especially those in non-remission have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Mitoxantrone hydrochloride liposome (Lipo-MIT) is a pegylated liposomal mitoxantrone formulation with promising efficacy and an acceptable safety profile in rescue treatment of R/R AML.There was no report of Lipo-MIT combination with thiotepa- busulfan-fludarabine(TBF)as an intensive conditioning regimen prior to allo-HSCT. This study aimed to explore the efficacy and safety of Lipo-MIT in combination with TBF as an intensive conditioning regimen before salvage allo-HSCT in R/R AML patients.

Methods: This is a single-arm,prospective clinical trial(NCT06385808).R/R AML patients in non-remission were enrolled for salvage allo-HSCT with an intensive conditioning regimen consisted of mitoxantrone hydrochloride liposome 24mg/m2 ivgtt d-7;thiotepa 5mg/kg ivgtt d-6~-5; Busulfan 0.8mg/kg q6h ivgtt d-4~-2; Fludarabine 50mg/m2 ivgtt d-4~-2. The primary endpoint was the cumulative incidence of relapse. Secondary endpoints included progression-free survival (PFS), overall survival (OS), times to neutrophil engraftment and platelet engraftment, acute and chronic graft versus host disease(GVHD)and non-hematological toxicity.

Results: Thirteen patients with R/R AML who underwent salvage allo-HSCT while in non-remission or with concomitant extramedullary leukemia at the first affiliated hospital of xi'an jiaotong university were enrolled, including 6 men and 7 women with a median age of 37 (16-53) years. A total of 9 cases were refractory, and 4 cases were relapsed.Six cased with FLT3-ITD mutation, one with TP53 mutation, 2 cases transformed from myelodysplastic syndromes,and one with ASXL1, ETV6 and K-RAS mutations.Nine patients in non-remission and 4 patients with central nervous system leukemia before transplantation. The proportion of blasts in bone marrow befo re transplantation was ranged from 6% to 75%.Ten cases underwent haploidentical allo-HSCT, 3 cases underwent matched sibling allo-HSCT.

The curative effect evaluation conducted between 14 and 21 days post-transplantation showed that the complete remission rate and the minimal residual disease (MRD) negativity rate was 100%. The median engraftment time of neutrophil and platelet were 11(9-13) days and 12(11-23) days respectively. Two cases had grade II-IV acute GVHD and one with chronic GVHD, one had hemorrhagic cystitis at one month post-transplantation, and one with post-transplant lymphoproliferative diseases at 44 days post-transplantation. The median follow-up time was 6 months.So far, all patients were all alive with negative MRD .The median PFS and OS time were not determined.

The most common non-hematological adverse events of Lipo-MIT combination with TBF included diarrhea (76.9%,10/13), oral mucositis(76.9%,10/13), gastrointestinal bleeding (23.1%,3/13), drug-induced liver damage (15.4%,2/13). All of these adverse events were improved after treatment.

Conclusion:Mitoxantrone hydrochloride liposome in combination with TBF as an intensive conditioning regimen before salvage allo-HSCT shows promising results in patients with R/R AML.

Keywords:Acute myeloid leukemia,salvage allogeneic hematopoietic stem cell transplantation, relapsed,refractory

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH