Di Ianni Mauro, Olioso Paola, Giancola Raffaella, Santarone Stella, Natale Annalisa, Papalinetti Gabriele, Villanova Ida, Baldoni Stefano, Di Tommaso Ambra, Bonfini Tiziana, Accorsi Patrizia, Di Bartolomeo Paolo
Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy.
Hematology Section, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Int J Hematol. 2017 Dec;106(6):860-864. doi: 10.1007/s12185-017-2292-3. Epub 2017 Jul 18.
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow). The patient received a first infusion of 2.5 × 10/kg Tregs derived from matched donor followed 7 days later by 5 × 10/kg Tcons. GvL effect was strongly evident as the percentage of leukemic cells decreased to 5%. A second infusion of Tregs (2.5 × 10/kg) and Tcons (2 × 10/kg) was performed. No GvHD was observed. Disease evaluation showed the absence of blastic cells at flow-cytometry, a normal caryotype and full donor chimerism. We also observed NOTCH1 down-regulation in peripheral blood. This new immunotherapy approach showed that Treg-protected DLI is effective in preventing GvHD and is associated with a strong GvL effect.
在接受单倍体造血干细胞移植（HSCT）的高危急性白血病患者中，采用调节性T细胞（Tregs）和常规T细胞（Tcons）进行过继性免疫治疗可预防急性和慢性移植物抗宿主病（GvHD），有利于移植后免疫重建，并伴有强大的移植物抗白血病（GvL）效应。通过一种特别创新的方法，我们为HSCT后早期复发的患者开发了一种受Treg保护的供体淋巴细胞输注（DLI）治疗方法，在此报告首例第二次全相合异基因HSCT后复发的急性早幼粒细胞白血病（APL，M3v）患者的治疗结果（骨髓中原始细胞占15%，供体细胞占75%）。该患者首先接受了一次来自匹配供体的2.5×10/kg Tregs输注，7天后又接受了5×10/kg Tcons输注。随着白血病细胞百分比降至5%，GvL效应明显显现。随后进行了第二次Tregs（2.5×10/kg）和Tcons（2×10/kg）输注。未观察到GvHD。疾病评估显示流式细胞术检测未发现原始细胞，核型正常且完全为供体嵌合型。我们还观察到外周血中NOTCH1下调。这种新的免疫治疗方法表明，受Treg保护的DLI在预防GvHD方面有效，并伴有强大的GvL效应。
