Division for Stem Cell Transplantation, Immunology and Intensive Care, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt, Germany.
Pediatric Hematology and Oncology, Muenster University Children's Hospital, Muenster, Germany.
Blood Adv. 2023 Jun 13;7(11):2436-2448. doi: 10.1182/bloodadvances.2022008981.
Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product. We performed a retrospective study inviting all CAR T-cell centers in Germany to participate. Eighty-one patients with pB-ALL were included. Twenty-eight days after CAR T-cell infusion, 71 patients (87.7%) were in complete response, and 8 (9.9%) were in nonremission. At 2 years, the probabilities of event-free survival (pEFS), relapse-free survival (pRFS), and overall survival (pOS) were 45.3%, 51.7%, and 53.2%, respectively. pEFS was not different in patients without (n = 16, 55.0%) vs with prior allo-HSCT (n = 65, 43.4%). In patients treated after allo-HSCT, the time to relapse after allo-HSCT was a strong predictor of outcome. Patients relapsing within 6 months of allo-HSCT had a disappointing pEFS of 18.4% (pOS = 16.0%); the pEFS for those relapsing later was 55.5% (pOS = 74.8%). Our study provides real-world experience in pediatric, adolescent, and young adult patients with ALL treated with Tisa-cel, where most patients were treated after having relapsed after allo-HSCT. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that patients with ALL after allo-HSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons.
患有前体 B 细胞急性淋巴细胞白血病 (pB-ALL) 的患者在异基因造血干细胞移植 (allo-HSCT) 后复发、多次复发或初始耐药的患者预后不良。靶向 CD19 的嵌合抗原受体 (CAR) T 细胞已成为有效的免疫疗法。Tisagenlecleucel (Tisa-cel) 是一种市售的自体 CD19 定向 CAR T 细胞产品。我们进行了一项回顾性研究,邀请德国所有的 CAR T 细胞中心参与。共纳入 81 例 pB-ALL 患者。CAR T 细胞输注后 28 天,71 例患者(87.7%)达到完全缓解,8 例患者(9.9%)未缓解。2 年时,无事件生存(pEFS)、无复发生存(pRFS)和总生存(pOS)的概率分别为 45.3%、51.7%和 53.2%。无既往 allo-HSCT(n=16,55.0%)与有既往 allo-HSCT(n=65,43.4%)的患者 pEFS 无差异。allo-HSCT 后治疗的患者,allo-HSCT 后复发时间是预后的强预测因素。allo-HSCT 后 6 个月内复发的患者 pEFS 较差,仅为 18.4%(pOS=16.0%);而晚于 6 个月复发的患者 pEFS 为 55.5%(pOS=74.8%)。本研究提供了使用 Tisa-cel 治疗儿童、青少年和年轻成人 ALL 患者的真实世界经验,大多数患者在 allo-HSCT 后复发后接受治疗。Tisa-cel 单次治疗的总缓解率为 45.3%。我们的新发现是,allo-HSCT 后发生 ALL 的患者,如果复发发生在 6 个月后,pEFS 要好得多,这可能有助于临床决策,并促使研究揭示原因。
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