Hervé P, Flesch M, Tiberghien P, Wijdenes J, Racadot E, Bordigoni P, Plouvier E, Stephan J L, Bourdeau H, Holler E
Bone Marrow Transplant Unit, Besançon, France.
Blood. 1992 Jun 15;79(12):3362-8.
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.
在一项多中心试点研究中，19例对传统治疗和单克隆抗白细胞介素-2受体抗体血清疗法难治的重度急性移植物抗宿主病（aGVHD）患者接受了体内输注单克隆抗肿瘤坏死因子α（TNFα）抗体（B-C7）治疗。10例患者由基因型相同的同胞供体移植，5例由HLA不匹配的家庭成员供体移植，4例由HLA匹配的无关供体移植。在B-C7治疗前，15例患者为IV级GVHD，4例为III级GVHD。所有病例中，患者均接受环孢素/甲氨蝶呤作为aGVHD预防用药。患者接受递增剂量的抗体（从0.1至0.4mg/kg）。抗体每日一次大剂量输注，共4天，然后隔天输注两次（共6剂）。无论使用何种剂量水平，治疗期间均未观察到副作用。19例患者中有8例外周血细胞计数发生变化，且似乎与B-C7无关。未观察到真正的完全缓解；8例患者达到非常好的部分缓解（42.6%），6例达到部分缓解（31.5%）。5例患者（26.4%）治疗无效。如有缓解，缓解出现较早（少于3天）。在14例有反应的患者中，肠道病变反应最佳（100%），其次是皮肤（85%）和肝脏（35.7%）病变。在11例可评估患者中的9例（81%）中，治疗中断时GVHD复发，中位延迟时间为3天（范围为2至120天）。除1例患者外，所有患者均死于aGVHD。2例患者未发生GVHD复发，在骨髓移植后13个月和18个月时仍存活。这项试点研究表明，单克隆抗TNFα抗体可能对一些重度难治性aGVHD患者有益，但在大多数情况下对预防GVHD复发无效。
