Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors
Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors
复制标题
DOI：
10.1016/j.bbmt.2016.12.636
复制
发表时间：
2017-03-01
影响因子：
4.3
通讯作者：
Aglietta, Massimo
中科院分区：
文献类型：
--
作者：
Carnevale-Schianca, Fabrizio;Caravelli, Daniela;Aglietta, Massimo
异基因造血细胞移植(HCT)仍然是治疗许多恶性血液病的唯一方法，但它受到高无复发死亡率(NRM)的限制，主要是由于移植物抗宿主病(GVHD)的不可预测的控制。最近，移植后的环磷酰胺在异基因骨髓移植中显示出改善了GVHD的控制。在这里，我们探讨了环磷酰胺在异基因外周血干细胞移植中的应用。高危恶性血液病患者接受了人类白细胞抗原相合的无关/亲缘供者的异基因PBSCT。GVHD的预防包括HCT后环磷酰胺50 mg/kg(+3天和+4天)和他克莫司/霉酚酸酯(T/MMF)(+5天前)。主要目标是急性和慢性移植物抗宿主病的累积发病率。在2011年3月至2015年5月期间，连续35名患者接受了建议的方案。所有患者在+28天停止使用MMF；他克莫司的中位停用时间为+113天。急性和慢性GVHD累积发生率分别为17%和7%，无IV级GVHD事件，仅2例患者需要慢性GVHD免疫抑制控制，无GVHD死亡。2年NRM、总存活率、无事件存活率和慢性移植物抗宿主病无事件存活率分别为3%、77%、54%和49%。移植物抗肿瘤效应得以维持，15名接受HCT且有疾病证据的患者中有5名(33%)有进一步的疾病反应。移植后的环磷酰胺+T/MMF联合策略有效地预防了HLA相合供者异基因PBSCT后的急性和慢性GVHD，并在不失去疾病控制效果或损害移植物抗肿瘤效应的情况下实现了前所未有的低NRM。这项试验在Clinicaltrials.gov上注册为NCT02300571。(C)2017年美国血液和骨髓移植学会。
Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. (C) 2017 American Society for Blood and Marrow Transplantation.