Ruxolitinib combined with decitabine-intensified modified busulfan/cyclophosphamide conditioning regimen reduces relapse after allogeneic hematopoietic stem cell transplantation in Acute Myeloid Leukemia

Abstract Allogeneic hematopoietic stem cell transplantation is the only radical treatment for high-risk acute myeloid leukemia (AML), but the traditional Bu/Cy pretreatment regimen is highly toxic and has a high recurrence rate after transplantation (the long-term survival rate is only 10-30%). Although the existing improved regimens such as sequential chemotherapy can reduce the leukemia burden, they lead to prolonged myelosuppression time (17-39 days) and a non-relapse mortality rate as high as 17.2%. There is an urgent need to develop new pretreatment regimens that have both strong anti-leukemia effects and low toxicity. Studies have found that the JAK-STAT signaling pathway is generally abnormally activated in hematological tumors such as AML. The objective response rate of Ruxolitinib (a JAK1/2 inhibitor) as a monotherapy for relapsed/refractory leukemia reached 45%. When combined with the demethylated drug decitabine, it can synergistically inhibit leukemia cells. Clinical data show that decitabine reduces the recurrence rate after transplantation by 20% (15.0% vs 38.3%), and the combination of the two has good safety. The main adverse reaction is grade 1-2 hematological toxicity. Our center innovatively proposed the Rux-Dec-mBu/Cy combined regimen: integrating Ruxolitinib (step-based dose reduction) and decitabine (20mg/m²/d) on the basis of the classic Bu/Cy. Previous single-arm studies have shown that the one-year recurrence rate of CR1 patients is 0%, and the incidence of toxicity above grade 3 is less than 11%. This study intends to conduct a multicenter randomized controlled trial to verify the superiority of this regimen in reducing recurrence after transplantation in patients with AML CR1. Its core advantage lies in simultaneously achieving anti-leukemia enhancement (through JAK-STAT targeting and epigenetic regulation) and controllable toxicity (The median grain deficiency time was shortened to 14 days). In order to analyze the effect of ruxolitinib combined with decitabine and enhanced modified benzalkone-cyclophosphamide pretreatment regimen on the recurrence rate within one year in patients with acute myeloid leukemia who achieved first complete remission. Our center conducted a prospective single-arm cohort study, and all the enrolled patients met the diagnostic criteria for AML CR1. All adopted the pretreatment regimen containing ruxolitinib combined with decitabine to enhance and modify benzalkone-cyclophosphamide. This article prospectively observed 32 patients who underwent allogeneic hematopoietic stem cell transplantation at the First Medical Center of the PLA General Hospital from September 2020 to June 2023. The cumulative recurrence rate one year after transplantation in AML CR1 patients (ClinicalTrials.gov ID:NCT04582604) who received Rux-Dec-mBu/Cy pretreatment. The observation results showed that the cumulative recurrence rate of 32 patients within one year was 5.26%. As of May 1, 2025, the median follow-up was 1085.5 (645-1683) days. Among them, 5 patients relapsed, 4 patients survived after recurrence, and 1 patient died of recurrence. The MRD was positive in the first bone marrow flow cytometry of 17 patients +28 days after transplantation. The overall survival rate one year after transplantation was 90.4%, the progression-free survival rate one year was 87.5%, the recurrence-free survival rate of graft-versus-host disease within one year was 81.25%, and the non-recurrence mortality rate one year was 9.38%. Four patients died, including one recurrence death and three non-recurrence deaths (one died of septic shock and two died of viral pneumonia). Therefore, we draw the conclusion that the ruxolitinib combined with decitabine intensive modified benzalkone-cyclophosphamide pretreatment regimen reduces recurrence after allogeneic hematopoietic stem cell transplantation in patients with AML CR1.