Department of Hematology and Cellular Therapy, Saint Antoine Hospital, AP-HP, Paris, France; UMRS 938, Inserm, Paris, France; Université Pierre et Marie Curie Paris VI, Sorbonne University, Paris, France.
Department of Hematology, Henri Becquerel Center, Rouen, France.
Biol Blood Marrow Transplant. 2018 May;24(5):1013-1021. doi: 10.1016/j.bbmt.2018.01.005. Epub 2018 Jan 11.
The results of conventional allogeneic stem cell transplantation (SCT) in refractory hematologic malignancies are poor. Sequential strategies have shown promising results in refractory acute myelogenous leukemia (AML), but have not been validated in a haploidentical (Haplo) transplant setting. We have developed a new sequential approach combining chemotherapy with broad antitumor activity (thiotepa 10 mg/kg, etoposide 400 mg/m, and cyclophosphamide 1600 mg/m from day -15 to day -10), followed after 3 days of rest by a reduced-intensity conditioning regimen (fludarabine 150 mg/m, i.v. busulfan 6.4 mg/kg, and thymoglobulin 5 mg/kg from day -6 to day -2). High-dose post-transplantation cyclophosphamide was added in cases with Haplo donors. Seventy-two patients (median age, 54 years) with a refractory hematologic malignancy (44 with acute myelogenous leukemia, 7 with acute lymphoblastic leukemia, 15 with myelodysplastic syndrome/myeloproliferative neoplasms, and 6 with lymphomas) were included in this retrospective multicenter study. Donors were Haplo (n = 27), matched related (MRD; n = 16), and unrelated (UD; n = 29). With a median follow-up of 21 months, the 2-year overall survival (OS) and event-free survival (EFS) were 54.7% and 49.3%, respectively, in recipients of Haplo transplants, 49.2% and 43.8%, respectively, in recipients of MRD transplants, and 37.9% and 28%, respectively, in recipients of UD transplants. Compared with UD, the outcomes were improved in Haplo in terms of the incidences of acute grade II-IV graft-versus-host disease (GVHD) (11.1% versus 41.4%; P < .001) and GVHD-free, relapse-free survival (44.4 versus 10.3%; P = .022). These results support the safety and efficacy of a thiotepa-based sequential approach in allogeneic SCT with a Haplo donor with post-transplantation immune modulation. Thus, in patients with refractory hematologic malignancies, there seems to be no benefit in searching for a UD when a Haplo donor is readily available.
常规异基因造血干细胞移植（SCT）在难治性血液系统恶性肿瘤中的疗效较差。序贯策略在难治性急性髓系白血病（AML）中显示出良好的效果，但尚未在单倍体（Haplo）移植环境中得到验证。我们开发了一种新的序贯方法，在难治性血液系统恶性肿瘤患者中，采用具有广泛抗肿瘤活性的化疗（噻替哌 10mg/kg、依托泊苷 400mg/m2 和环磷酰胺 1600mg/m2，从第 -15 天至第 -10 天），在 3 天休息后进行低强度预处理方案（氟达拉滨 150mg/m2、静脉注射白消安 6.4mg/kg 和胸腺球蛋白 5mg/kg，从第 -6 天至第 -2 天）。在 Haplo 供者的情况下，添加高剂量移植后环磷酰胺。这项回顾性多中心研究纳入了 72 例难治性血液系统恶性肿瘤患者（中位年龄 54 岁）（44 例急性髓系白血病，7 例急性淋巴细胞白血病，15 例骨髓增生异常综合征/骨髓增殖性肿瘤，6 例淋巴瘤）。供者为 Haplo（n=27）、匹配相关（MRD；n=16）和无关（UD；n=29）。中位随访 21 个月后，Haplo 移植患者的 2 年总生存率（OS）和无事件生存率（EFS）分别为 54.7%和 49.3%，MRD 移植患者分别为 49.2%和 43.8%，UD 移植患者分别为 37.9%和 28%。与 UD 相比，Haplo 在急性 II-IV 级移植物抗宿主病（GVHD）的发生率（11.1%比 41.4%；P<0.001）和无 GVHD、无复发生存（44.4%比 10.3%；P=0.022）方面的结果得到改善。这些结果支持在 Haplo 供者的异基因 SCT 中使用基于噻替哌的序贯方法的安全性和有效性，并进行移植后免疫调节。因此，在难治性血液系统恶性肿瘤患者中，当 Haplo 供者易于获得时，似乎没有必要寻找 UD。
