Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia
Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia
复制标题
DOI：
10.1182/bloodadvances.2020003739
复制
发表时间：
2021-03-02
期刊：
影响因子：
7.5
通讯作者：
Velardi, Andrea
中科院分区：
文献类型：
--
作者：
Pierini, Antonio;Ruggeri, Loredana;Velardi, Andrea
异基因造血干细胞移植（HSCT）是根除高危急性髓细胞白血病（AML）的最有效治疗方法。在这里，我们提供了一种新的HLA半相合HSCT方案的数据，该方案解决了剩下的两个主要未满足的医疗需求：白血病复发和慢性移植物抗宿主病（cGVHD）。50例AML患者入组研究。预处理方案包括年龄不超过50岁患者的全身照射和年龄51至65岁患者的全骨髓/淋巴照射。照射后进行噻替派、氟达拉滨和环磷酰胺。患者在第-4天接受2 × 106/kg供体调节性T细胞输注，随后在第-1天接受1 × 106/kg供体常规T细胞输注，在第0天接受平均10.7 × 106 +/- 3.4 × 106/kg纯化CD 34+造血祖细胞输注。移植后未给予药物GVHD预防。患者实现了完全供体型植入。15例患者发生了≥ 2级急性GVHD（aGVHD）。15例aGVHD患者中有12例存活，不再接受免疫抑制治疗。仅1例患者发生中/重度cGVHD。10例患者无复发死亡。仅2例患者复发。因此，在中位随访29个月时，中度/重度cGVHD/无复发生存率的概率为75%（95%置信区间，71%-78%）。一种新的HLA半相合HSCT策略，将年龄适应性清髓性预处理方案与调节性和常规T细胞过继免疫治疗相结合，在50例中位年龄为53岁的AML患者中实现了前所未有的cGVHD/无复发生存率。
Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment in eradicating high-risk acute myeloid leukemia (AML). Here, we present data from a novel HLA-haploidentical HSCT protocol that addressed the 2 remaining major unmet medical needs: leukemia relapse and chronic graft-versus-host disease (cGVHD). Fifty AML patients were enrolled in the study. The conditioning regimen included total body irradiation for patients up to age 50 years and total marrow/lymphoid irradiation for patients age 51 to 65 years. Irradiation was followed by thiotepa, fludarabine, and cyclophosphamide. Patients received an infusion of 2 x 10(6)/kg donor regulatory T cells on day -4 followed by 1 x 106/kg donor conventional T cells on day -1 and a mean of 10.7 x 10(6) +/- 3.4 x 10(6)/kgpurified CD34+ hematopoietic progenitor cells on day 0. No pharmacological GVHD prophylaxis was administered posttransplantation. Patients achieved full donor-type engraftment. Fifteen patients developed grade >= 2 acute GVHD (aGVHD). Twelve of the 15 patients with aGVHD were alive and no longer receiving immunosuppressive therapy. Moderate/severe cGVHD occurred in only 1 patient. Nonrelapse mortality occurred in 10 patients. Only 2 patients relapsed. Consequently, at a median follow-up of 29 months, the probability of moderate/severe cGVHD/relapse-free survival was 75% (95% confidence interval, 71%-78%). A novel HLA-haploidentical HSCT strategy that combines an age-adapted myeloablative conditioning regimen with regulatory and conventional T-cell adoptive immunotherapy resulted in an unprecedented cGVHD/relapse-free survival rate in 50 AML patients with a median age of 53 years.