Laberko Alexandra, Idarmacheva Aishat, Glushkova Svetlana, Pershin Dmitry, Shelikhova Larisa, Maschan Michael, Maschan Alexei, Balashov Dmitry
Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Translational and Clinical Research Institute, Newcastle University; Newcastle-upon-Tyne, United Kingdom.
Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Transplant Cell Ther. 2022 Mar;28(3):172.e1-172.e4. doi: 10.1016/j.jtct.2021.11.022. Epub 2021 Dec 4.
We recently demonstrated that TCRαβ+/CD19+ graft depletion successfully prevents severe acute and chronic graft-versus-host disease (GVHD) in pediatric patients with primary immunodeficiencies (PID) receiving transplants from both matched unrelated and mismatched related donors. However, in all patients, short-term post-hematopoietic stem cell transplantation (HSCT) immunosuppressive therapy (IST) was used. There are limited data on TCRαβ+/CD19+ graft depletion with no post-HSCT IST implementation. In the current study 74 PID patients who underwent first HSCT from matched unrelated (n=51) or mismatched related donors (n=23) with TCRαβ+/CD19+ graft depletion were included. All received as a conditioning regimen a combination of treosulfan with fludarabine and either melphalan or thiotepa. In all, thymoglobulin 5 mg/kg (days -5, -4, -3) and rituximab at day -1 were used. In 48 patients, various approaches to short-term post-transplantation IST were used, and 26 patients received no post-HSCT IST. The rates of engraftment, acute and chronic GVHD, survival, and mortality were similar in those who received and did not receive IST, with a slightly higher incidence of graft rejection in patients not receiving IST: 19% in the non-IST group against 13% in the IST group (P = .41). The incidence of cytomegalovirus reactivation was 50% and 39% (P = .50) and Epstein-Barr virus reactivation 10% and 0 (P = .20) in the IST and non-IST groups, respectively. No grade 4 adverse events were seen in both groups, although in 19 of 40 (47.5%) patients receiving calcineurin inhibitors, the therapy was discontinued before day 45. More robust immune recovery with both T- and B-lymphocytes was observed in the non-IST group. To conclude, TCRαβ+/CD19+ in combination with particular serotherapy effectively prevents severe acute and chronic GVHD in PID. Regarding remaining risks of infectious complications and additional drug-related toxicity, there are no benefits to post-HSCT IST use in these patients.
我们最近证明，TCRαβ⁺/CD19⁺移植物清除术成功预防了原发性免疫缺陷病（PID）儿科患者接受匹配无关供体和不匹配相关供体移植后的严重急性和慢性移植物抗宿主病（GVHD）。然而，所有患者在造血干细胞移植（HSCT）后均使用了短期免疫抑制治疗（IST）。关于未实施HSCT后IST的TCRαβ⁺/CD19⁺移植物清除的数据有限。在本研究中，纳入了74例接受TCRαβ⁺/CD19⁺移植物清除的PID患者，这些患者首次接受来自匹配无关供体（n = 51）或不匹配相关供体（n = 23）的HSCT。所有患者均接受白消安联合氟达拉滨以及美法仑或塞替派作为预处理方案。总共使用了胸腺球蛋白5mg/kg（第-5、-4、-3天）和利妥昔单抗在第-1天。48例患者采用了各种短期移植后IST方法治疗，26例患者未接受HSCT后IST。接受和未接受IST的患者在植入率、急性和慢性GVHD、生存率及死亡率方面相似，未接受IST的患者移植排斥发生率略高：非IST组为19%，而IST组为13%（P = 0.41）。巨细胞病毒再激活发生率在IST组和非IST组分别为50%和39%（P = 0.50），EB病毒再激活发生率分别为10%和0（P = 0.20）。两组均未出现4级不良事件，尽管在40例接受钙调神经磷酸酶抑制剂治疗的患者中有19例（47.5%）在第45天前停止了治疗。在非IST组观察到T淋巴细胞和B淋巴细胞的免疫恢复更强。总之，TCRαβ⁺/CD19⁺联合特定的血清疗法可有效预防PID患者的严重急性和慢性GVHD。关于感染并发症的剩余风险和额外的药物相关毒性，这些患者使用HSCT后IST并无益处。
