Phase I-II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease.
Phase I-II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease.
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单克隆抗肿瘤坏死因子α抗体治疗难治性严重急性移植物抗宿主病的 I-II 期试验。
DOI：
10.1182/blood.v79.12.3362.3362
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发表时间：
1992
期刊：
影响因子：
20.3
通讯作者：
E. Holler
中科院分区：
文献类型：
--
作者：
P. Hervé;M. Flesch;P. Tiberghien;J. Wijdenes;E. Racadot;P. Bordigoni;E. Plouvier;J. Stéphan;H. Bourdeau;E. Holler
在一项多中心试点研究中，19 名患有严重急性移植物抗宿主病 (aGVHD) 且对常规疗法和单克隆抗白细胞介素 2 受体抗体血清疗法无效的患者通过体内输注单克隆抗肿瘤坏死因子 α (TNF α) 抗体 (B-C7) 进行治疗。 10 名患者来自基因型相同的兄弟姐妹，5 名来自 HLA 不匹配的家庭成员，4 名来自 HLA 匹配的无关捐赠者。 B-C7治疗前，15名患者患有IV级GVHD，4名患者患有III级GVHD。在所有病例中，患者均接受环孢素/甲氨蝶呤作为 aGVHD 预防。患者接受递增剂量的抗体（从 0.1 至 0.4 毫克/公斤）。抗体每天以推注方式输注，持续 4 天，然后每隔一天输注两次（6 剂）。无论使用何种剂量水平，在治疗期间均未观察到副作用。 19 名患者中有 8 名发生了外周血细胞计数的变化，并且似乎与 B-C7 无关。没有观察到真正完全的反应；八名患者取得了非常好的部分缓解（42.6%），六名患者取得了部分缓解（31.5%）。 5 名患者（26.4%）的治疗无效。如果存在，则响应会提前发生（不到 3 天）。在 14 名有反应的患者中，肠道病变反应最好 (100%)，其次是皮肤 (85%) 和肝脏 (35.7%) 病变。 11 名可评估患者中有 9 名 (81%) 在中位延迟 3 天（范围为 2 至 120 天）停止治疗时复发 GVHD。除一名外，其余所有人均死于 aGVHD。两名患者没有出现 GVHD 复发，并且在骨髓移植后 13 个月和 18 个月仍然存活。这项初步研究表明，单克隆抗 TNF α 抗体可能对某些患有严重难治性 aGVHD 的患者有益，但在大多数情况下无法有效预防 GVHD 复发。
In a multicenter pilot study, 19 patients with severe acute graft-versus-host disease (aGVHD) refractory to conventional therapy and serotherapy with a monoclonal anti-interleukin-2 receptor antibody were treated by in vivo infusion of a monoclonal anti-tumor necrosis factor alpha (TNF alpha) antibody (B-C7). Ten patients were grafted from a genotypically identical sibling, five from an HLA-mismatched family member, and four from an HLA-matched unrelated donor. Before B-C7 treatment, 15 patients had grade IV and four had grade III GVHD. In all cases, patients received cyclosporine/methotrexate as aGVHD prophylaxis. Patients were administered increasing doses of antibody (from 0.1 to 0.4 mg/kg). The antibody was infused in bolus daily for 4 days and then every other day twice (6 doses). No side effects were observed during treatment regardless of the dose level used. Changes in peripheral blood cell counts occurred in 8 of the 19 patients and appeared to be unrelated to B-C7. No truly complete response was observed; eight patients achieved a very good partial response (42.6%) and six a partial response (31.5%). The treatment was ineffective in five patients (26.4%). When present, the response occurred early (less than 3 days). In the 14 responding patients, gut lesions responded best (100%), followed by skin (85%) and liver (35.7%) lesions. In 9 of 11 evaluable patients (81%), GVHD recurred when treatment was discontinued in a median delay of 3 days (range, 2 to 120 days). All except one died from aGVHD. Two patients did not experience GVHD recurrence and are still alive 13 and 18 months post-bone marrow transplantation. This pilot study shows that a monoclonal anti-TNF alpha antibody may be of benefit to some patients with severe refractory aGVHD, but is ineffective to prevent GVHD recurrence in the majority of cases.
影响因子：
20.3
作者：
P. Martin;G. Schoch;L. D. Fisher;Vera Byers;C. Anasetti;F. Appelbaum;Patrick G. Beatty;K. Doney;George B. McDonald;J. Sanders;K. Sullivan;R. Storb;E. Thomas;R. Witherspoon;Pavel Lomen;John Hannigan;J. Hansen
通讯作者：
P. Martin;G. Schoch;L. D. Fisher;Vera Byers;C. Anasetti;F. Appelbaum;Patrick G. Beatty;K. Doney;George B. McDonald;J. Sanders;K. Sullivan;R. Storb;E. Thomas;R. Witherspoon;Pavel Lomen;John Hannigan;J. Hansen
血清肿瘤坏死因子α与人类急性移植物抗宿主病相关。
影响因子：
6.2
作者：
Symington,FW;Pepe,MS;Chen,AB;Deliganis,A
通讯作者：
Deliganis,A