Department of Hematology-BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece.
BReMeL Βiopharmaceutical and Regenerative Medicine Laboratories, Thessaloniki, Greece.
Biol Blood Marrow Transplant. 2020 Aug;26(8):e183-e191. doi: 10.1016/j.bbmt.2020.04.003. Epub 2020 Apr 15.
Patients with refractory or relapsed (R/R) B cell acute lymphoblastic leukemia (B-ALL) and highly aggressive B cell non-Hodgkin lymphoma (B-NHL) have a very dismal prognosis and limited treatment options. The advent of chimeric antigen receptor (CAR) T cell therapy constitutes a milestone in current cell and gene therapies, covering the unmet need of treatment of high-risk patients and bringing immunotherapies one step closer toward cancer therapeutics, including hematologic malignancies. CAR T cells targeting CD19 antigen have shown startling remission rates in heavily pretreated B-ALL and B-NHL patients, in whom CAR T cell therapy may sometimes be their last-resort treatment. However, a high proportion of these patients evade immune surveillance by CAR T cells losing their initial deep responses, which leads to disease recurrence as either CD19-positive or CD19-negative relapse. As a result, many investigators have questioned the need for consolidative allogeneic hematopoietic stem cell transplantation (allo-HCT) after CAR T cell therapy, once a patient has achieved remission. There remains much controversy regarding whether CAR T cells should be a bridge therapy to allo-HCT or a definitive treatment, owing to the paucity of strong evidence-based data. In this context, here we review the existing data regarding the necessity, safety, and outcomes of allo-HCT performed after autologous anti-CD19 CAR T cell therapy in B-ALL and B-NHL patients.
对于难治性或复发性(R/R)B 细胞急性淋巴细胞白血病(B-ALL)和侵袭性高 B 细胞非霍奇金淋巴瘤(B-NHL)患者,其预后极差,治疗选择有限。嵌合抗原受体(CAR)T 细胞疗法的出现是当前细胞和基因治疗的一个里程碑,满足了高危患者的治疗需求,并使免疫疗法在癌症治疗方面更进一步,包括血液系统恶性肿瘤。针对 CD19 抗原的 CAR T 细胞在经过大量预处理的 B-ALL 和 B-NHL 患者中显示出惊人的缓解率,在这些患者中,CAR T 细胞疗法有时可能是他们的最后治疗选择。然而,相当一部分患者通过 CAR T 细胞逃避免疫监视,失去初始的深度反应,从而导致疾病复发,无论是 CD19 阳性还是 CD19 阴性复发。因此,许多研究人员质疑在 CAR T 细胞治疗后是否需要进行巩固性同种异体造血干细胞移植(allo-HCT),一旦患者达到缓解。由于缺乏强有力的循证数据,CAR T 细胞是否应作为 allo-HCT 的桥接治疗或确定性治疗,仍存在很大争议。在这种情况下,我们在此回顾了关于自体抗 CD19 CAR T 细胞治疗后在 B-ALL 和 B-NHL 患者中进行 allo-HCT 的必要性、安全性和结果的现有数据。
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