Oakhill A, Pamphilon D H, Potter M N, Steward C G, Goodman S, Green A, Goulden P, Goulden N J, Hale G, Waldmann H, Cornish J M
Royal Hospital for Sick Children, Bristol.
Br J Haematol. 1996 Sep;94(3):574-8. doi: 10.1046/j.1365-2141.1996.d01-1834.x.
Allogeneic sibling bone marrow transplantation (BMT) is the recommended treatment for relapsed childhood acute lymphoblastic leukaemia (ALL), but appropriate donors are only available in 30% of cases. Unfortunately, BMT from unrelated donors (UD) has been associated with high rates of severe graft-versus-host disease (GvHD) and transplant-related mortality (TRM). In an attempt to improve outcome in UD-BMT we have assessed the impact of T-cell depletion using CAMPATH-1 (anti-CD52) monoclonal antibodies in 50 consecutively referred patients with relapsed ALL in second remission. All were previously treated according to MRC protocols UKALL X and XI, and then given chemotherapy on MRC R1 from relapse until UD-BMT, 19 patients had relapsed on and 31 off therapy. Patients and donors were fully matched at HLA-A, -B, -DR and -DQ loci in 29 cases and mismatched in 21 (four mismatched for more than one antigen). Pre-transplant conditioning comprised CAMPATH-1G, cyclophosphamide and total body irradiation. Bone marrow was T-cell depleted in vitro using CAMPATH-1 antibodies. Additional GvHD prophylaxis consisted of cyclosporin A (42 cases), cyclosporin plus methotrexate (four) or none (four). 47 patients engrafted. The incidence of acute GvHD was very low: two patients with grade II disease in the matched group, four with grade II-IV in the mismatched group. Only four patients have chronic GvHD. The actuarial event-free survival (EFS) at 2 years is 53%, with no significant difference between the matched and mismatched group. Further leukaemic relapse was the most important cause of failure. These results are similar to the most favourable published reports for HLA-matched sibling BMT in relapsed ALL.
异基因同胞骨髓移植（BMT）是复发性儿童急性淋巴细胞白血病（ALL）的推荐治疗方法，但仅30%的病例能获得合适供者。不幸的是，无关供者（UD）骨髓移植与严重移植物抗宿主病（GvHD）和移植相关死亡率（TRM）的高发生率相关。为改善UD-BMT的疗效，我们评估了使用CAMPATH-1（抗CD52）单克隆抗体清除T细胞对50例连续转诊的处于第二次缓解期的复发性ALL患者的影响。所有患者此前均按照英国医学研究委员会（MRC）UKALL X和XI方案进行治疗，然后在复发后至UD-BMT期间接受MRC R1方案化疗，19例患者在治疗期间复发，31例在治疗期外复发。29例患者的患者与供者在HLA-A、-B、-DR和-DQ位点完全匹配，21例不匹配（4例多个抗原不匹配）。移植前预处理包括CAMPATH-1G、环磷酰胺和全身照射。使用CAMPATH-1抗体在体外对骨髓进行T细胞清除。额外的GvHD预防措施包括环孢素A（42例）、环孢素加甲氨蝶呤（4例）或不采取预防措施（4例）。47例患者植入成功。急性GvHD的发生率非常低：匹配组2例患者发生Ⅱ级疾病，不匹配组4例发生Ⅱ - Ⅳ级疾病。仅4例患者发生慢性GvHD。2年时的无事件生存率（EFS）为53%，匹配组和不匹配组之间无显著差异。白血病进一步复发是失败的最重要原因。这些结果与已发表的关于复发性ALL中HLA匹配同胞BMT的最有利报告相似。
