Foell Juergen, Kleinschmidt Katharina, Jakob Marcus, Troeger Anja, Corbacioglu Selim
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Regensburg, Regensburg, Germany.
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital of Regensburg, Regensburg, Germany.
Hematol Oncol Stem Cell Ther. 2020 Jun;13(2):98-105. doi: 10.1016/j.hemonc.2019.12.006. Epub 2020 Mar 12.
Sickle cell disease (SCD) is an inherited disorder; despite significant improvements in supportive care, SCD continues to cause substantial morbidity, mortality, and reduced life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only widely available curative therapy for SCD, which is offered as a standard of care for patients with a matched sibling donor (MSD). Donor availability is limited to a minority of patients. Thus, αβ/CD3-depleted haploidentical HSCT, as an efficient means for depletion of graft-versus-host disease (GvHD)-mediating T cells, can be offered as an alternative curative therapy, particularly for nonmalignant diseases such as SCD. Out of 38 patients with advanced stage SCD, 25 were transplanted with CD3/CD19- or T-cell receptor αβ/CD19 T-cell-depleted peripheral stem cell grafts (T-haplo-HSCT group), whereas 13 transplanted from MSD (MSD group); both groups received an almost identical conditioning regimen. Engraftment was achieved in all. However, in the T-haplo-HSCT group, three patients succumbed to an uncontrolled cytomegalovirus pneumonitis, a macrophage activation syndrome, and a major blood group incompatibility with a late graft failure and multiorgan failure. The overall survival was 88% and 100% in T-haplo-HSCT and MSD groups, respectively. None of our patients developed a Glucksberg Grade III-IV acute GvHD. Four patients (16%) in the T-haplo-HSCT group and two patients (15%) in the MSD group developed a steroid-sensitive, mild-to-moderate chronic GvHD that resolved within 18 months posttransplant. These results are encouraging and demonstrate the feasibility, safety, and efficacy of T-haplo-HSCT in advanced stage SCD in children and adults, thus offering a curative alternative to majority of patients.
镰状细胞病（SCD）是一种遗传性疾病；尽管支持性治疗有了显著改善，但SCD仍继续导致大量发病、死亡，并缩短预期寿命。异基因造血干细胞移植（HSCT）是目前唯一广泛可用的SCD治愈性疗法，对于有匹配同胞供体（MSD）的患者，这是一种标准治疗方案。供体的可及性仅限于少数患者。因此，αβ/CD3 去除的单倍体相合HSCT，作为一种有效去除移植物抗宿主病（GvHD）介导性T细胞的方法，可以作为一种替代性治愈性疗法提供，特别是对于SCD等非恶性疾病。在38例晚期SCD患者中，25例接受了CD3/CD19或T细胞受体αβ/CD19 T细胞去除的外周干细胞移植（单倍体相合HSCT组），而13例接受了MSD移植（MSD组）；两组接受了几乎相同的预处理方案。所有患者均实现植入。然而，在单倍体相合HSCT组中，3例患者死于无法控制的巨细胞病毒肺炎、巨噬细胞活化综合征以及严重血型不相容伴晚期移植物失败和多器官衰竭。单倍体相合HSCT组和MSD组的总生存率分别为88%和100%。我们的患者均未发生Glucksberg III-IV级急性GvHD。单倍体相合HSCT组4例患者（16%）和MSD组2例患者（15%）发生了对类固醇敏感的轻至中度慢性GvHD，在移植后18个月内缓解。这些结果令人鼓舞，并证明了单倍体相合HSCT在儿童和成人晚期SCD中的可行性、安全性和有效性，从而为大多数患者提供了一种治愈性选择。
