Cavazzana-Calvo M, Bensoussan D, Jabado N, Haddad E, Yvon E, Moskwa M, Tachet des Combes A, Buisson M, Morand P, Virion J M, Le Deist F, Fischer A
Etablissement de Transfusion Sanguine-Hôpital Necker, Paris, France.
Br J Haematol. 1998 Nov;103(2):543-51. doi: 10.1046/j.1365-2141.1998.00972.x.
HLA-mismatched bone marrow transplantation (BMT) is hampered by three major complications: graft rejection, acute graft-versus-host disease (aGVHD) and delayed immune reconstitution. Infusion of anti-LFA1 plus anti-CD2 monoclonal antibodies (MAb), combined with ex-vivo T-cell depletion of the graft, was efficient in preventing graft rejection and aGVHD. Nevertheless, disease-free survival was limited by the high frequency of lethal infections, including EBV-induced lymphoproliferative disease (BLPD), which originates mostly from donor B cells, with an incidence of 5-30%. To decrease the rate of this complication, ex-vivo B-cell depletion was attempted. This study compares a group of 19 patients who received a T- and B-cell-depleted marrow from an HLA-mismatched related donor with a retrospective control group of 19 patients, who had received T-cell-depleted marrow by the same method. The level of T-cell depletion was similar in the two groups. For B-cell depletion, two different methods were compared. The median number of B cells infused in the study group was 0.46/kg. Engraftment and aGVHD incidence were similar in the two groups. No EBV donor-derived BPLD occurred in the study group, compared with seven in the control group, four of whom died because of EBV-BPLD. Event-free survival was significantly different between the two groups. We conclude that ex-vivo B-cell depletion of the graft may be a useful means of preventing EBV-BPLD, and warrants further study on a larger group of patients.
人类白细胞抗原（HLA）不匹配的骨髓移植（BMT）受到三种主要并发症的阻碍：移植物排斥、急性移植物抗宿主病（aGVHD）和免疫重建延迟。输注抗淋巴细胞功能相关抗原1（anti-LFA1）加抗CD2单克隆抗体（MAb），并结合对移植物进行体外T细胞清除，在预防移植物排斥和aGVHD方面是有效的。然而，无病生存期受到致死性感染高发生率的限制，包括由EB病毒（EBV）诱导的淋巴细胞增殖性疾病（BLPD），其大多起源于供体B细胞，发生率为5% - 30%。为降低这种并发症的发生率，尝试进行体外B细胞清除。本研究将一组19例接受来自HLA不匹配相关供体的T细胞和B细胞清除骨髓的患者与一组19例采用相同方法接受T细胞清除骨髓的回顾性对照组患者进行比较。两组的T细胞清除水平相似。对于B细胞清除，比较了两种不同的方法。研究组输注的B细胞中位数为0.46/kg。两组的植入率和aGVHD发生率相似。研究组未发生源自EBV供体的BPLD，而对照组有7例，其中4例因EBV - BPLD死亡。两组的无事件生存期有显著差异。我们得出结论，对移植物进行体外B细胞清除可能是预防EBV - BPLD的一种有用方法，值得在更大规模的患者群体中进一步研究。
