Yalniz Fevzi F, Hefazi Mehrdad, McCullough Kristen, Litzow Mark R, Hogan William J, Wolf Robert, Alkhateeb Hassan, Kansagra Ankit, Damlaj Moussab, Patnaik Mrinal M
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Department of Pharmacy, Mayo Clinic, Rochester, Minnesota.
Biol Blood Marrow Transplant. 2017 Sep;23(9):1478-1484. doi: 10.1016/j.bbmt.2017.05.001. Epub 2017 May 8.
Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first-line treatment; however, less than one-half of patients achieve durable remission. Studies suggest that TNF-α, a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-α therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD. Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17% complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14% PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had infectious complications within 12 weeks of initiation of infliximab. These infections included 40 bacterial infections, 6 invasive fungal infections, and 5 viral reactivations. Twelve patients (34%) died secondary to infections. Overall survival at 12 weeks and 6 months from the start of infliximab therapy was 37% (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to complications from GVHD and infections. In conclusion; the use of infliximab therapy in patients with SR-aGVHD is associated with a modest poorly sustained response along with a heightened risk of severe infections. Future studies with more effective and less toxic therapies are needed for these patients.
急性移植物抗宿主病（aGVHD）是异基因造血细胞移植（HCT）后发病和死亡的主要原因。糖皮质激素是一线治疗药物；然而，不到一半的患者能实现持久缓解。研究表明，肿瘤坏死因子-α（TNF-α）是预处理期间从骨髓释放的一种细胞因子，参与了aGVHD的发病机制。我们回顾性评估了英夫利昔单抗治疗35例类固醇难治性（SR）aGVHD患者的疗效。英夫利昔单抗以10 mg/kg的剂量静脉给药，每周给药一次，中位给药4剂（范围为1至6剂）。4周时的总缓解率为40%（完全缓解[CR]为17%，部分缓解[PR]为23%），8周时为23%（CR为9%，PR为14%），12周时为17%（均为CR）。29例（83%）患者在开始使用英夫利昔单抗后的12周内出现感染并发症。这些感染包括40例细菌感染、6例侵袭性真菌感染和5例病毒再激活。12例患者（34%）死于感染。从开始使用英夫利昔单抗治疗起，12周和6个月时的总生存率分别为37%（35例中的13例）和17%（35例中的6例）；大多数死亡继发于GVHD和感染并发症。总之，在SR-aGVHD患者中使用英夫利昔单抗治疗与适度且维持不佳的缓解相关，同时严重感染风险增加。这些患者需要未来开展更有效且毒性更低的治疗研究。
