Soiffer R J, Murray C, Mauch P, Anderson K C, Freedman A S, Rabinowe S N, Takvorian T, Robertson M J, Spector N, Gonin R
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
J Clin Oncol. 1992 Jul;10(7):1191-200. doi: 10.1200/JCO.1992.10.7.1191.
Acute and chronic graft-versus-host disease (GVHD) continues to be the major causes of morbidity and mortality after allogeneic bone marrow transplantation (BMT). In this study, we have evaluated the clinical effects of selective in vitro T-cell depletion of donor allogeneic bone marrow by using a single monoclonal antibody ([MoAb] anti-T12, CD6) and rabbit complement. This antibody recognizes mature T cells, but not other cellular elements such as natural-killer (NK) cells, B cells, and myeloid precursors.
From August 1983 to April 1991, 112 consecutive adult patients with hematologic malignancies underwent BMT with bone marrow from HLA-identical sibling donors. Marrow was harvested and depleted of mature T lymphocytes ex vivo by the use of three rounds of incubation with an anti-T12 antibody and rabbit complement. The preparative regimen consisted of cyclophosphamide and fractionated total body irradiation (TBI) in 108 patients. No patients received prophylactic immune suppression post-BMT. Purgation by anti-T12 was used as the only method for the prevention of GVHD.
Twenty patients (18%) developed acute GVHD (grade 2 to 4); only eight patients developed chronic GVHD. The incidence of GVHD did not increase significantly with age. Only three of 112 patients (2.7%) exhibited acute graft failure. One patient developed late graft failure that was associated with cytomegalovirus (CMV) infection. Within the subset of 50 patients who had not previously undergone unsuccessful conventional therapy (acute leukemia in first remission or chronic myelogenous leukemia [CML] in stable phase), we estimated by the Kaplan-Meier method that the probability of disease-free survival was 50% at 3 years post-BMT, with a median follow-up of 44 months. The treatment-related mortality rate in this group was only 14% and was independent of patient age.
We conclude that selective in vitro T-cell depletion with an anti-T12 monoclonal antibody effectively reduces the incidence of both acute and chronic GVHD after allogeneic BMT without compromising engraftment. Moreover, depletion of CD6-positive cells from donor marrow obviates the need to administer immune suppressive medications to the majority of patients. This approach reduces the morbidity and mortality of allogeneic BMT and permits the BMT of older patients.
急慢性移植物抗宿主病（GVHD）仍然是异基因骨髓移植（BMT）后发病和死亡的主要原因。在本研究中，我们评估了使用单克隆抗体（[MoAb]抗-T12，CD6）和兔补体对供体异基因骨髓进行体外选择性T细胞清除的临床效果。该抗体识别成熟T细胞，但不识别其他细胞成分，如自然杀伤（NK）细胞、B细胞和髓系前体细胞。
1983年8月至1991年4月，112例连续的成年血液系统恶性肿瘤患者接受了来自 HLA 相同同胞供体的骨髓BMT。采集骨髓并通过与抗-T12抗体和兔补体进行三轮孵育在体外清除成熟T淋巴细胞。108例患者的预处理方案包括环磷酰胺和分次全身照射（TBI）。BMT后没有患者接受预防性免疫抑制。抗-T12清除作为预防GVHD的唯一方法。
20例患者（18%）发生急性GVHD（2至4级）；仅8例患者发生慢性GVHD。GVHD的发生率并未随年龄显著增加。112例患者中仅3例（2.7%）出现急性移植失败。1例患者发生与巨细胞病毒（CMV）感染相关的晚期移植失败。在50例此前未经历过传统治疗失败（首次缓解期急性白血病或稳定期慢性粒细胞白血病[CML]）的患者亚组中，通过Kaplan-Meier法估计，BMT后3年无病生存概率为50%，中位随访时间为44个月。该组的治疗相关死亡率仅为14%，且与患者年龄无关。
我们得出结论，用抗-T12单克隆抗体进行体外选择性T细胞清除可有效降低异基因BMT后急性和慢性GVHD的发生率，且不影响植入。此外，从供体骨髓中清除CD6阳性细胞使大多数患者无需使用免疫抑制药物。这种方法降低了异基因BMT的发病率和死亡率，并允许老年患者进行BMT。
