供者淋巴细胞输注治疗异基因造血干细胞移植后EB病毒相关的淋巴细胞增殖性疾病的疗效和安全性

目的 采用控制数量的供者淋巴细胞输注(DLI)治疗EB病毒(EBV)相关的淋巴细胞增殖性疾病(PTLD),观察其有效性和安全性.方法 2006年11月到2009年11月移植的患者,临床或病理诊断EBV相关的PTLD采用DLI治疗者纳入研究.采用COBE血球分离机应用淋巴细胞程序采集白细胞,首选原供者,次选直系亲缘供者,冻存外周血采集物(G-PB)与移植时输入的外周血干细胞(PBSC)组分相同.控制输入的单个核细胞(PBMC)在(0.5～1.0)×108/kg.原基础免疫抑制剂预防移植物抗宿主病(GVHD),观察疗效及其副作用.结果 PTLD患者9例,输注13例次,输入外周血PBMC 0.8(0.16～1.03)× 108/kg,CD3+T淋巴细胞4.2(1.6～5.7)×107/kg.7例半相合移植患者采用了原供者,有效率为7/7,完全缓解率为6/7,退热中位时间2(1～5)d,淋巴结缩小中位时间6(1～14)d;7例中6例发生GVHD,均为轻中度,得到控制.至今无病存活3例.2例非亲缘HSCT采用了半相合供者的外周血白细胞,仅获得短暂部分疗效.结论 在配型不合/半相合移植中,采用原供者控制细胞数量的DLI并免疫抑制剂预防GVHD治疗EBV相关的PTLD安全有效.最佳方案尚需进一步研究.

The efficacy and safety of donor lymphocyte infusion to treat Epstein-Barr virus associated lymphoproliferative diseases after allogeneic hematopoietic stem cell transplantation

Objective To analyse our series patients' data to assess its efficacy and safety of donor lymphocyte infusion (DLI) for Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) after allogeneic hematopoietic stem cell transplantation (HSCT). Methods Patients received HSCT from November 2006 to November 2009 and diagnosed as EBV associated PTLD by pathological or clinical methods were enrolled in this study. Lymphocyte was prepared by COBE collector.Related haplo-donors were the alternative if the original donors was unavailable. A range of mononuclear cell (MNC) dose of (0.5-1.0) × 108/kg was designed and the expected number of T lymphocyte included was at level of 107/kg. Cyclosporine (CsA) trough concentration was kept in a therapeutic level. Results Nine patients with PTLD received DLI 13 times, the median number of PBMC infused was 0.8 (0.16-1.03) ×108/kg, CD3+T cell number was 4.2 (1.6-5.7) × 107/kg. Seven patients received peripheral blood mononuclear cells (PBMC) from original haplo-identical donors, with 7 response and 6 complete remission.Defervescence occurred after 2 ( 1-5 ) d, and adenopathy began to recover in 6 ( 1-14 ) d after the initial infusion of leukocytes. Graft versus host diseases (GVHD) occurred in 6 recipients out of 7 evaluable patients, and all were controlled successfully. Three patients survived for 38, 23 and 3 months after PTLD.Conclusion In this small series cases, infusion of controlled dose of lymphocyte from primary donor is an effective and safe therapy for EBV associated PTLD after mismatched/haploidentical HSCT while the optimal regimen needs to be further studied.