Reduced Intensity Condition of ATG Based Haploidentical Hematopoietic Stem Cell Transplantation in Elderly or Unfit Patients
Authors: Pan Mingyue , Wu Yibo , Yang Luxin , Shi Jimin , Lai Xiaoyu , Liu Lizhen , Zhao Yanmin , Yu Jian , Jie Sun , Zheng Weiyan , Wu Wenjun , Cai Zhen , Huang He , Luo Yi 
Published: December 2023

Aims: Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of ATG based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in elderly or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG based haploidentical HSCT.

Methods: We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30mg/m²/kg 6 days combined with busulfan 3.2mg/kg 2 days (Bu2) or 3 days (Bu3).

Results: The median age of patients in the entire cohort was 60 (32 - 67) years with a median follow-up of 496 (83 - 2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8% - 85.1%) and 61.4% (95% CI, 48.8% - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8 % (95% CI, 4.8% - 19.6%) and 9.7 % (95% CI, 0.0% - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9% - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5% - 33.7%) and 11.6% (95% CI, 2.2% - 21.9 %) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5%-85.3%) in Bu2 and 85.5%（95% CI:73.0%-100%) in Bu3 group respectively(P=0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0%-74.8%) in Bu2 and 72.6% (95% CI:55.5%-95.5%) in Bu3 group respectively (P=0.045). The 2-year IR or 2-year NRM were not significantly different between Bu2 and Bu3 group(P&gt;0.05). In multivariable analysis, RIC regimen of Bu3 had superior DFS and lower RI than Bu2 group respectively [HR 0.41, 95% CI 0.16-1.01; P=0.05; HR 0.33, 95% CI 0.11-0.99; P=0.047].

Conclusion: The RIC regime of ATG based haploidentical HSCT is a safe and effective treatment option for patients who are elderly or have poor functional status, making them unable to tolerate intensive chemotherapy. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in DFS, thus providing more favorable post-transplantation clinical outcomes.