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经部分 T 细胞清除 PBSC 移植的儿童具有有利的免疫恢复和低 GvHD 发生率。

Favorable immune recovery and low rate of GvHD in children transplanted with partially T cell-depleted PBSC grafts.

机构信息

Department of General Pediatrics, Hematology/Oncology, University Children's Hospital, Tuebingen, 72076, Germany.

Department of Hematology, Oncology and Stem Cell- Transplantation, University Children's Hospital, Wuerzburg, 97080, Germany.

出版信息

Bone Marrow Transplant. 2019 Jan;54(1):53-62. doi: 10.1038/s41409-018-0212-7. Epub 2018 May 24.


DOI:10.1038/s41409-018-0212-7
PMID:29795418
Abstract

Transplantation of peripheral blood stem cells (PBSC) from matched unrelated donors (MUD) is still associated with a significant risk for graft vs. host disease (GvHD), especially in pediatric patients receiving grafts from adult donors containing high amounts of T cells. Here, we present long-term follow-up results on 25 pediatric patients, (acute leukemia n = 15, NHL n = 3, CML n = 3, MDS n = 5), transplanted with CD34 or CD133 positively selected PBSC from MUDs supplemented with an add-back of 1 × 10/kg body weight (kgBW) unselected T cells resulting in a median T-cell depletion (TCD) of 1.97 log. A total of 24/25 (96%) patients had primary engraftment. Early T-cell recovery was significantly improved compared to patients receiving CD34-selected grafts without T-cell add-back and similar to patients receiving unmanipulated bone marrow. GvHD incidence was low with 8/4% aGvHD grade II/III, no grade IV and 13% limited cGvHD. In total, 16/25 (64%) patients are alive after a median follow-up of 10 years. Five-year event-free survival (EFS) was 68%, relapse probability 24% and transplantation-related mortality (TRM) 12%. Thus, in PBSC allotransplants from MUD, partial TCD with serotherapy and CSA/MTX prophylaxis, can effectively reduce GvHD without hampering engraftment and immune reconstitution.

摘要

异基因外周血造血干细胞(PBSC)移植来自匹配的非亲缘供体(MUD)仍然与移植物抗宿主病(GvHD)的风险显著相关,尤其是在接受来自含有大量 T 细胞的成人供体的移植物的儿科患者中。在这里,我们报告了 25 例儿科患者的长期随访结果,(急性白血病 n=15,NHL n=3,CML n=3,MDS n=5),接受来自 MUD 的 CD34 或 CD133 阳性选择 PBSC 移植,补充 1×10/kg 体重(kgBW)未经选择的 T 细胞,导致中位 T 细胞耗竭(TCD)为 1.97 对数。25/25(96%)例患者获得原发性植入。与未进行 T 细胞添加的 CD34 选择移植物的患者相比,早期 T 细胞恢复明显改善,与接受未处理骨髓的患者相似。GVHD 发生率低,8/4%为 aGVHD Ⅱ/Ⅲ级,无 4 级,13%为局限性 cGVHD。在中位随访 10 年后,25/25(64%)例患者存活。5 年无事件生存(EFS)为 68%,复发率为 24%,移植相关死亡率(TRM)为 12%。因此,在来自 MUD 的 PBSC 同种异体移植中,使用血清疗法和 CSA/MTX 预防进行部分 TCD 可有效降低 GvHD 的发生,而不会影响植入和免疫重建。

相似文献

[1]
Favorable immune recovery and low rate of GvHD in children transplanted with partially T cell-depleted PBSC grafts.

Bone Marrow Transplant. 2018-5-24

[2]
CD34+ Stem Cell Selection and CD3+ T Cell Add-Back from Matched Unrelated Adult Donors in Children with Primary Immunodeficiencies and Hematological Diseases.

Transplant Cell Ther. 2021-5

[3]
Alemtuzumab, Dual Graft-versus-Host Disease Prophylaxis, and Lower CD3 T Cell Doses Equalize Rates of Acute and Chronic Graft-versus-Host Disease in Pediatric Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation with Matched Unrelated Donor Peripheral Blood Stem Cells or Bone Marrow Grafts.

Transplant Cell Ther. 2024-3

[4]
Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation.

Biol Blood Marrow Transplant. 2019-5-11

[5]
Superior GVHD-free, relapse-free survival for G-BM to G-PBSC grafts is associated with higher MDSCs content in allografting for patients with acute leukemia.

J Hematol Oncol. 2017-7-4

[6]
T cell depletion utilizing CD34(+) stem cell selection and CD3(+) addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients.

Br J Haematol. 2012-2-8

[7]
Unrelated donor peripheral blood stem cell transplants incorporating pre-transplant in-vivo alemtuzumab are not associated with any increased risk of significant acute or chronic graft-versus-host disease.

Br J Haematol. 2011-3-8

[8]
Clinical separation of cGvHD and GvL and better GvHD-free/relapse-free survival (GRFS) after unrelated cord blood transplantation for AML.

Bone Marrow Transplant. 2017-1

[9]
Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts.

J Clin Invest. 2015-7-1

[10]
Allogeneic transplantation of G-CSF mobilized peripheral blood stem cells from unrelated donors: a retrospective analysis.

Haematologica. 2000-8

引用本文的文献

[1]
Immunomonitoring of Stage IV Relapsed Neuroblastoma Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation and Subsequent GD2 (ch14.18/CHO) Antibody Treatment.

Front Immunol. 2021

[2]
Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis.

Blood Adv. 2020-5-12

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