Strüßmann Tim, Hermes Philipp, Ihorst Gabriele, Finke Jürgen, Duque-Afonso Jesús, Engelhardt Monika, Duyster Justus, Marks Reinhard
Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Clinical Trials Unit, Faculty of Medicine, University Medical Center, University of Freiburg, Freiburg, Germany.
Eur J Haematol. 2025 Jan;114(1):139-146. doi: 10.1111/ejh.14320. Epub 2024 Oct 9.
High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B-cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high-dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow-up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, p = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression-free survival (PFS) (HR 1.80 CI 1.11-2.92, p = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86-2.56, p = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40-1.38, p = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22-0.94, p = 0.032). Age 60-69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60-69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders.
大剂量化疗（HDCT）后进行自体干细胞移植（ASCT）广泛应用于弥漫性大B细胞淋巴瘤患者。HDCT/ASCT在老年/身体状况不佳的患者中与发病率增加相关。我们回顾性评估了在弥漫性大B细胞淋巴瘤患者中使用降低强度预处理的情况。我们的研究纳入了2005年至2019年在我们机构接受治疗的146例60岁及以上的患者；86例患者接受了标准强度预处理（SI组），采用BEAM或TEAM方案（卡莫司汀或塞替派、依托泊苷、阿糖胞苷、美法仑）。60例患者接受了降低强度的大剂量预处理（RI组），采用BM方案（卡莫司汀、美法仑，43.3%）、TM方案（塞替派、美法仑，16.7%）、卡莫司汀或白消安塞替派方案（38.4%）或苯达莫司汀美法仑方案（1.7%）。中位随访时间为62.4个月。我们在SI组和RI组中观察到了相当的毒性。RI组3年时的累积复发率更高（30.8%对23.4%，p = 0.034）。非复发死亡率（NRM）没有差异。在单因素分析中，SI与RI预处理导致了更好的无进展生存期（PFS）（风险比[HR] 1.80，置信区间[CI] 1.11 - 2.92，p = 0.017），但总体生存期（OS）没有更好（HR 1.48，CI 0.86 - 2.56，p = 0.152）。在多因素分析中，我们观察到PFS没有差异（HR 0.74，CI 0.40 - 1.38），p = 0.345），并且RI预处理有OS更好的趋势（HR 0.45，CI 0.22 - 0.94，p = 0.032）。60 - 69岁与≥70岁以及ASCT前缓解是预测更好PFS的唯一因素。与更好OS相关的因素是RI预处理、60 - 69岁与≥70岁、东部肿瘤协作组（ECOG）0与≥1的体能状态、大块病灶以及之前1线与≥2线治疗。总之，ASCT前的RI预处理在老年患者中可能是可行的，并且在校正了几个显著的混杂因素后导致了相当结果。
