Carnevale-Schianca Fabrizio, Caravelli Daniela, Gallo Susanna, Coha Valentina, D'Ambrosio Lorenzo, Vassallo Elena, Fizzotti Marco, Nesi Francesca, Gioeni Luisa, Berger Massimo, Polo Alessandra, Gammaitoni Loretta, Becco Paolo, Giraudo Lidia, Mangioni Monica, Sangiolo Dario, Grignani Giovanni, Rota-Scalabrini Delia, Sottile Antonino, Fagioli Franca, Aglietta Massimo
Medical Oncology, Hematopoietic Stem Cells Unit, Turin Metropolitan Transplant Center, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
Medical Oncology, Hematopoietic Stem Cells Unit, Turin Metropolitan Transplant Center, Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.
Biol Blood Marrow Transplant. 2017 Mar;23(3):459-466. doi: 10.1016/j.bbmt.2016.12.636. Epub 2016 Dec 27.
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.
异基因造血细胞移植（HCT）仍然是许多血液系统恶性肿瘤的唯一治愈性疗法，但它受到高非复发死亡率（NRM）的限制，主要源于对移植物抗宿主病（GVHD）的不可预测控制。最近，移植后环磷酰胺在异基因骨髓HCT中显示出对GVHD的控制有所改善。在此，我们探索环磷酰胺在异基因外周血干细胞移植（alloPBSCT）中的应用。高危血液系统恶性肿瘤患者接受来自HLA匹配的无关/相关供体的alloPBSCT。GVHD预防措施包括移植后环磷酰胺50mg/kg（第+3天和第+4天）与他克莫司/霉酚酸酯（T/MMF）联合使用（第+5天起）。主要目标是急性和慢性GVHD的累积发生率。在2011年3月至2015年5月期间，连续35例患者接受了所提议的方案。所有患者在第+28天停用MMF；他克莫司的中位停药时间为第+113天。急性和慢性GVHD的累积发生率分别为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，且无因GVHD导致的死亡。两年的NRM、总生存率、无事件生存率和慢性GVHD无事件生存率分别为3%、77%、54%和49%。移植物抗肿瘤效应得以维持，因为15例接受HCT且有疾病证据的患者中有5例（33%）经历了进一步的疾病缓解。移植后环磷酰胺+T/MMF联合策略有效预防了来自HLA匹配供体的alloPBSCT后的急性和慢性GVHD，并实现了前所未有的低NRM，同时在疾病控制方面不失疗效或不损害移植物抗肿瘤效应的发展。该试验在clinicaltrials.gov上注册为NCT02300571。
