Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Scientific Institute for Research and Healthcare (IRCCS) Bambino Gesù Children's Hospital, Rome, Italy.
Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Università degli Studi della Campania Luigi Vanvitelli, Caserta, Italy.
Blood Adv. 2021 Mar 9;5(5):1333-1339. doi: 10.1182/bloodadvances.2020003707.
We report on the outcome of 24 patients with Fanconi anemia (FA) lacking an HLA matched related or unrelated donor, given an HLA-haploidentical T-cell receptor αβ (TCRαβ+) and CD19+ cell-depleted hematopoietic stem cell transplantation (HSCT) in the context of a prospective, single-center phase 2 trial. Sustained primary engraftment was achieved in 22 (91.6%) of 24 patients, with median time to neutrophil recovery of 12 days (range, 9-15 days) and platelet recovery of 10 days (range, 7-14 days). Cumulative incidences of grade 1 to 2 acute graft-versus-host disease (GVHD) and chronic GVHD were 17.4% (95% confidence interval [CI], 5.5%-35.5%) and 5.5% (95% CI, 0.8%-33.4%), respectively. The conditioning regimen, which included fludarabine, low-dose cyclophosphamide and, in most patients, single-dose irradiation was well tolerated; no fatal transplant-related toxicity was observed. With a median follow-up of 5.2 years (range, 0.3-8.7 years), the overall and event-free survival probabilities were 100% and 86.3% (95% CI, 62.8%-95.4%), respectively (2 graft failures and 1 case of poor graft function were considered as events). The 2 patients who experienced primary graft failure underwent a subsequent successful HSCT from the other parent. This is the first report of FA patients given TCRαβ+/CD19+-depleted haplo-HSCT in the context of a prospective trial, and the largest series of T-cell-depleted haplo-HSCT in FA reported to date. This trial was registered at www.clinicaltrials.gov as #NCT01810120.
我们报告了 24 例范可尼贫血（FA）患者的结果，这些患者缺乏与 HLA 匹配的相关或无关供体，在一项前瞻性、单中心 2 期试验中，接受了 HLA 单倍体相容 T 细胞受体αβ（TCRαβ+）和 CD19+细胞耗竭的造血干细胞移植（HSCT）。24 例患者中有 22 例（91.6%）实现了持续的原发性植入，中性粒细胞恢复的中位时间为 12 天（范围，9-15 天），血小板恢复的中位时间为 10 天（范围，7-14 天）。1 至 2 级急性移植物抗宿主病（GVHD）和慢性 GVHD 的累积发生率分别为 17.4%（95%可信区间[CI]，5.5%-35.5%）和 5.5%（95% CI，0.8%-33.4%）。包括氟达拉滨、低剂量环磷酰胺和大多数患者单次照射的预处理方案耐受性良好；未观察到致命的移植相关毒性。中位随访 5.2 年（范围，0.3-8.7 年）后，总生存率和无事件生存率分别为 100%和 86.3%（95% CI，62.8%-95.4%）（2 例移植失败和 1 例移植物功能不良被视为事件）。2 例发生原发性移植失败的患者随后从另一位父母接受了成功的 HSCT。这是首例在前瞻性试验中接受 TCRαβ+/CD19+-耗竭单倍体 HSCT 的 FA 患者报告，也是迄今为止报告的 FA 患者中 T 细胞耗竭单倍体 HSCT 最大系列。该试验在 www.clinicaltrials.gov 上注册，编号为 #NCT01810120。
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