F/C + AIECy预处理方案在自体造血干细胞移植治疗侵袭性B细胞 NHL中的疗效观察

Effect of auto-HSCT using conditioning regimen F/C + AIECy for aggressive B cell NHL

  • 摘要:
    背景 自体造血干细胞移植(autologous hematopoietic stem cell transplantation,Auto-HSCT)在年轻高危险度分层的侵袭性B细胞非霍奇金淋巴瘤(B-cell non-Hodgkin’s lymphoma,B-NHL)患者治疗中作为一线巩固方案,逐渐成为国内外专家的共识。现行预处理方案下,依然有超过30%患者移植后复发,故预处理方案仍有改进空间。
    目的 探究预处理方案为氟达拉滨或克拉屈滨联合阿糖胞苷 + 伊达比星 + 依托泊苷 + 环磷酰胺(F/C + AIECy)的自体造血干细胞移植一线巩固治疗高危、中高危侵袭性B-NHL的安全性和有效性。
    方法 回顾性分析2015年1月—2020年1月我院应用本预处理方案的高危、中高危侵袭性B-NHL患者临床资料,分析干细胞采集情况、预处理相关不良反应、植入情况、患者疗效及生存与复发情况。
    结果 共纳入32例患者,男20例,女12例,中位年龄42(范围:15 ~ 60)岁。采集单个核细胞和CD34+ 细胞的中位数分别为11.55(范围:8.05 ~ 14.76) × 108/kg、4.56(范围:1.58 ~ 15.24) × 106/kg。所有患者均获得造血重建,植入率为 100%;白细胞植入的中位时间为10(范围:7 ~ 20) d,血小板植入的中位时间为14(范围:12 ~ 30) d。移植期间感染发生率为68.75%,其他2级及以上不良反应发生率:黏膜炎18.75%、呕吐或腹泻46.88%、肝损害15.63%、出血6.25%,无预处理相关脏器衰竭和死亡事件。移植后3个月评估总缓解率由移植前的56.25%提升至84.38%(P=0.027)。中位随访时间38.5(范围:10 ~ 83)个月,8例复发,4例死亡,3年复发率为21.87%,32例患者1年总生存(overall survival,OS)率和无进展生存(progression-free survival,PFS)率分别为93.8%、86.9%,3年OS率和PFS率分别为86.5%、75.6%,5年OS率和PFS率分别为78.6%、68.0%。
    结论 F/C + AIECy预处理方案的Auto-HSCT一线巩固治疗年轻高危险度分层侵袭性B细胞NHL安全有效,对提高缓解率、降低移植后复发及改善生存有益。

     

    Abstract:
    Background  Autologous hematopoietic stem cell transplantation (Auto-HSCT) is still a consolidation treatment choice for young patients with high-risk, high-intermediate-risk aggressive B-cell non-Hodgkin’s lymphoma (B-NHL) as frontline therapy. With the current pre-treatment plan, more than 30% of patients still experience recurrence after transplantation, so continuous improvement is still needed for the pre-treatment plan.
    Objective To investigate the safety and effectiveness of Auto-HSCT using tumor-ablative conditioning regimen F/C + AIECy (Fludarabine/Cladribine + Idarubicin + Cytarabine + Etoposide + Cytoxan) for patients with aggressive B cell non-Hodgkin's lymphoma (B-NHL).
    Methods Clinical data about 32 patients with high-risk, high-intermediate-risk aggressive B-NHL received above-mentioned therapeutic regimen from January 2015 to January 2020 were analyzed retrospectively, and conditioning-related toxicity, engraftment, survival and relapse rate were evaluated.
    Results A total of 32 patients were included, including 20 males and 12 females, with a median age of 42 (range: 15-60) years. The medians of collected mononuclear cells and CD34 + cells were 11.55 (range: 8.05-14.76) × 108/kg and 4.56 (range: 1.58-15.24) × 106/kg, respectively. All patients had successfully completed hematopoietic reconstruction with the implantation rate of 100%, and the median of neutrophil and platelet reconstitution time was 10 (range: 7-20) days and 14 (range: 12-30) days in these cases. The incidence of infection during transplantation was 68.75%, and during transplantation the incidence rates of adverse reaction in grade 2 or higher were as follows: mucositis accounting for 18.75%, nausea and vomiting for 46.88%, liver injury for 15.63%, bleeding for 6.25%. No conditioning-related organs' failure and mortality events were found. The complete remission (CR) rate of all patients was significantly higher at 3 months after transplantation compared with before transplantation (56.25% vs 84.38%, P=0.027). The median follow-up time was 38.5 (range: 10-83) months, during which disease progression occurred in 8 cases, death occurred in 4 cases, and the 3-year relapse rate of all patients was 21.87%. The 1-year overall survival (OS) rate and progression-free survival (PFS) rate was 93.8% and 86.9%, the 3-year OS rate and PFS rate was 86.5% and 75.6%, the 5-year OS rate and PFS rate was 78.6% and 68%. Conclusion Auto-HSCT using conditioning regimen F/C + AIECy is safe and effective for young patients with high-risk, high-intermediate-risk aggressive B- NHL, and it possess a certain effect for increasing CR rate after transplantation.

     

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