Masetti Riccardo, Leardini Davide, Gottardi Francesca, Baccelli Francesco, Ottaviano Giorgio Antonio Maria, Vendemini Francesca, Saglio Francesco, Pierri Filomena, Algeri Mattia, Del Bufalo Francesca, Merli Pietro, Prete Arcangelo, Cesaro Simone, Ussowicz Marek, Faraci Maura, Zecca Marco, Fagioli Franca, Balduzzi Adriana, Dalle Jean-Hugues, Locatelli Franco, Pagliara Daria
Pediatric Hematology and Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Science (DIMEC), University of Bologna, Bologna, Italy.
Br J Haematol. 2025 Sep;207(3):929-937. doi: 10.1111/bjh.70004. Epub 2025 Jul 21.
Human leukocyte antigen (HLA)-haploidentical haematopoietic cell transplantation (haplo-HCT) is a suitable salvage strategy in children with haematological malignancies experiencing either relapse or graft failure (GF) after the first HCT. Data comparing outcomes of transplant strategies using either TCRαβ/CD19 depletion (TCRαβ) or post-transplant cyclophosphamide (PTCy) are currently lacking. This retrospective, multicentre study included children with haematological malignancies who received a second haplo-HCT, in which either TCRαβ depletion or PTCy was used as the graft-versus-host disease (GvHD) prophylaxis strategy. Primary outcomes included overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). Overall, 123 patients were analysed, 56 receiving PTCy and 67 receiving TCRαβ. Median age at transplant was 9.1 years (range, 1.0-24.7 years). Relapse and GF were the transplant indications in 96 and 27 patients respectively. The 24-month OS [56.8% (95% CI: 42.5%-71.1%) vs. 43.2% (95% CI: 31.4%-55.1%)] and EFS [44.1% (95% CI: 30.3%-57.8%) vs. 35.8% (95% CI: 24.3%-47.3%)] did not differ between PTCy or TCRαβ cohorts. The CIR [34.0% (95% CI: 23.1%-50.1%) vs. 37.3% (95% CI: 27.3%-50.8%), p = 0.28] and NRM [18.9% (95% CI: 10.7%-33.4%) vs. 25.3% (95% CI: 16.8%-38.2%), p = 0.48] were comparable. Cumulative incidence of 100-day of any-grade acute GvHD was higher in the PTCy cohort [55.3% (95% CI: 43.7%-70.4%) vs. 32.8% (95% CI: 23.3%-46.2%), p = 0.02], with non-statistically significant differences for grade II-IV and grade III-IV. The 24-month cumulative incidence of chronic GvHD was higher in the PTCy cohort [38.8% (95% CI: 27.6%-54.6%) vs. 11.9% (95% CI: 6.2%-22.8%), p < 0.01], including moderate-severe forms [15.3% (95% CI: 8.1%-29.1%) vs. 1.4% (95% CI: 0.2%-10.4%), p < 0.01]. Infectious complications were comparable except for a higher adenovirus reactivation rate in the TCRαβ group (14.3% vs. 29.9%, p = 0.04). PTCy and TCRαβ offer comparable clinical outcomes in the setting of second haplo-HCT, although PTCy is associated with a higher incidence of GvHD and lower adenovirus reactivation.
人类白细胞抗原（HLA）半相合造血细胞移植（haplo-HCT）是血液系统恶性肿瘤患儿首次HCT后出现复发或移植物失败（GF）时合适的挽救策略。目前缺乏比较使用TCRαβ/CD19清除（TCRαβ）或移植后环磷酰胺（PTCy）的移植策略结果的数据。这项回顾性多中心研究纳入了接受第二次haplo-HCT的血液系统恶性肿瘤患儿，其中TCRαβ清除或PTCy被用作移植物抗宿主病（GvHD）预防策略。主要结局包括总生存期（OS）、无事件生存期（EFS）、复发累积发生率（CIR）和非复发死亡率（NRM）。总体而言，分析了123例患者，56例接受PTCy，67例接受TCRαβ。移植时的中位年龄为9.1岁（范围1.0 - 24.7岁）。复发和GF分别是96例和27例患者的移植指征。PTCy组和TCRαβ组的24个月OS[56.8%（95%CI：42.5% - 71.1%）对43.2%（95%CI：31.4% - 55.1%）]和EFS[44.1%（95%CI：30.3% - 57.8%）对35.8%（95%CI：24.3% - 47.3%）]无差异。CIR[34.0%（95%CI：23.1% - 50.1%）对37.3%（95%CI：27.3% - 50.8%），p = 0.28]和NRM[18.9%（95%CI：10.7% - 33.4%）对25.3%（95%CI：16.8% - 38.2%），p = 0.48]相当。PTCy组任何级别急性GvHD的100天累积发生率更高[55.3%（95%CI：43.7% - 70.4%）对32.8%（95%CI：23.3% - 46.2%），p = 0.02]，II - IV级和III - IV级差异无统计学意义。PTCy组慢性GvHD的24个月累积发生率更高[38.8%（95%CI：27.6% - 54.6%）对11.9%（95%CI：6.2% - 22.8%），p < 0.01]，包括中重度形式[15.3%（95%CI：8.1% - 29.1%）对1.4%（95%CI：0.2% - 10.4%），p < 0.01]。除TCRαβ组腺病毒再激活率较高（14.3%对29.9%，p = 0.04）外，感染并发症相当。在第二次haplo-HCT中，PTCy和TCRαβ提供了相当的临床结局，尽管PTCy与更高的GvHD发生率和更低的腺病毒再激活相关。
