In vivo infusion of anti-CD11a/LFA-1 antibody for prevention and treatment of severe GVHD in HLA-nonidentical bone marrow transplantation : Its serum concentrations and biological effects.

同种异体骨髓移植（BMT）仍然是患者唯一的治疗方法，但hla相同的供体不能提供的唯一可能。在这种情况下，严重的移植物抗宿主病（GVHD）的情况下，未经治疗的骨髓移植和移植排斥的情况下，t细胞枯竭的BMT是主要障碍。为了克服这些障碍，使用了抗cd11a /LFA-1单克隆抗体（mAb），并取得了良好的结果。在这项研究中，一名范可尼贫血患者接受了hla不相同，t细胞耗尽的BMT和抗cd11a /LFA-1单抗（25.3）来预防移植排斥，但没有成功重建造血。在另一名接受hla相同BMT但患有类固醇抵抗的严重急性GVHD的患者中，给予CD11a/LFA-1单抗治疗该疾病。连续注射抗体7 d后，严重胃肠道疾病得到改善，但皮肤出疹没有太大变化。采用本研究建立的酶联免疫吸附法（ELASA）检测血清单抗浓度。单次注射6小时后，血清抗体水平在8小时达到峰值，然后下降，估计半衰期为40小时。每日注射导致血清mAb浓度累积增加，在第5天达到最大值。停药后血清mAb水平迅速下降。在治疗期间，白细胞减少和中性粒细胞减少逐渐发生，但淋巴细胞计数基本保持不变。CD4+ t细胞群减少，导致CD4/CD8比值异常低。淋巴细胞对裂丝原（PHA, con A， PWM）的成母反应在治疗期间存在缺陷，但在停止输注后完全恢复。结果表明，输注抗cd11a /LFA-1单抗是控制抗甾体抵抗性GVHD的另一种策略。

HLA-nonidentical bone marrow transplantation (BMT) remains the only possiblility for patients for whom allogeneic BMT in the only curative approach but a HLA-identical donor can not be offered. In this context, severe graft-versus-host disease (GVHD) in case of untreated marrow transplant and graft rejection in case of T-cell depleted BMT are major obstracles. To overcome these obstrucles an anti-CD11a/LFA-1 monoclonal antibody (mAb) has been used with promising results. In this study, a patient with Fanconi's anemia underwent HLA-nonidentical, T-cell depleted BMT and an anti-CD11a/LFA-1 mAb (25.3) was used to prevent graft rejection without success to reconstitute hematopoiesis. In another patient who underwent HLA-identical BMT but suffered from steroid-resistant severe acute GVHD, the CD11a/LFA-1 mAb was given to treat the illness. With 7-day successive infusions of the antibody severe gastrointestinal illness was improved, but skin eruption was not much changed. Serum concentrations of the mAb were assayed by enzyme-linked immunosorbent assay (ELASA) established in this study. With a single 6-h infusion the serum antibody level reached a peak at 8h and then declined with an estimated half-life of 40 h. Daily infusion caused a cumulative increase of serum mAb concentration reaching a maximum at the 5th day. After discontinuation the serum mAb levels droped rapidly. During the treatment leukopenia and neutropenia developed gradually but lylmpyocyte counts remained unchanged much. CD4+ T-cell population decreased resulting in abnormally low CD4/CD8 ratios. Blastogenic responses of lymphocytes to mitogens (PHA, con A, PWM) were defective during the treatment but completely restored after stopping the infusion. The results obtained suggest that infusion of anti-CD11a/LFA-1 mAb is an alternative strategy in controlling stroid-resistant GVHD.