Division of Hematology, AOU "Città della Salute e della Scienza di Torino", Torino, Italy.
Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy.
Sci Rep. 2024 Jul 23;14(1):16946. doi: 10.1038/s41598-024-67906-w.
In the frontline high-dose phase 3 FIL-MCL0208 trial (NCT02354313), 8% of enrolled mantle cell lymphoma (MCL) patients could not be randomised to receive lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) due to inadequate hematological recovery and 52% of those who started LEN, needed a dose reduction due to toxicity. We therefore focused on the role played by CD34 + hematopoietic stem cells (PBSC) harvesting and reinfusion on toxicity and outcome. Overall, 90% (n = 245) of enrolled patients who underwent the first leukapheresis collected ≥ 4 × 10 PBSC/kg, 2.6% (n = 7) mobilized < 4 × 10 PBSC/kg and 7.7% (n = 21) failed the collection. Similar results were obtained for the planned second leukapheresis, with only one patient failing both attempts. Median count of reinfused PBSC was 5 × 10/kg and median time to recovery from neutropenia G4 was 10 days from ASCT. No impact of mobilizing subtype or number of reinfused PBSC on hematological recovery and LEN dose reduction was noted. At a median follow-up of 75 months from ASCT, PFS and OS of transplanted patients were 50% and 73%, respectively. A long lasting G4 neutropenia after ASCT (> 10 days) was associated with a worse outcome, both in terms of PFS and OS. In conclusion, although the harvesting procedures proved feasible for younger MCL patients, long-lasting cytopenia following ASCT remains a significant issue: this can hinder the administration of effective maintenance therapies, potentially increasing the relapse rate and negatively affecting survival outcomes.
在前线高剂量 3 期 FIL-MCL0208 试验（NCT02354313）中，由于血液学恢复不足，8%的入组套细胞淋巴瘤（MCL）患者无法随机接受来那度胺（LEN）维持治疗与观察治疗，而在接受自体干细胞移植（ASCT）后；由于毒性，52%开始接受 LEN 治疗的患者需要减少剂量。因此，我们专注于 CD34+造血干细胞（PBSC）采集和回输对毒性和结果的作用。总体而言，90%（n=245）接受第一次白细胞分离术的入组患者采集的 PBSC 量≥4×10/kg，2.6%（n=7）动员的 PBSC 量<4×10/kg，7.7%（n=21）采集失败。计划的第二次白细胞分离术也获得了类似的结果，只有一名患者两次尝试都失败了。回输的 PBSC 的中位数计数为 5×10/kg，从 ASCT 中性粒细胞 4 级恢复的中位数时间为 10 天。动员亚型或回输的 PBSC 数量对血液学恢复和 LEN 剂量减少没有影响。从 ASCT 开始随访中位数为 75 个月时，移植患者的 PFS 和 OS 分别为 50%和 73%。ASCT 后持久的中性粒细胞 4 级中性粒细胞减少症（>10 天）与较差的预后相关，无论是在 PFS 还是 OS 方面。总之，尽管采集程序对年轻的 MCL 患者来说是可行的，但 ASCT 后长期的细胞减少仍然是一个重大问题：这可能会阻碍有效的维持治疗的给药，从而增加复发率，并对生存结果产生负面影响。
