Ueda Oshima Masumi, Storer Barry E, Qiu Huiying, Chauncey Thomas, Asch Julie, Boyer Michael W, Giaccone Luisa, Flowers Mary, Mielcarek Marco, Storb Rainer, Maloney David G, Sandmaier Brenda M
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Washington.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Transplant Cell Ther. 2021 Feb;27(2):163.e1-163.e7. doi: 10.1016/j.jtct.2020.10.016. Epub 2020 Dec 11.
Nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) from HLA-identical related donors using cyclosporine (CSP) and mycophenolate mofetil (MMF) for postgrafting immunosuppression is effective therapy for hematologic cancers. However, graft-versus-host-disease (GVHD) remains a major cause of morbidity and mortality. Pilot data suggested lower acute GVHD incidence with tacrolimus/MMF compared to historical experience using CSP/MMF after nonmyeloablative HCT. In a phase II multicenter trial, we evaluated the effect of tacrolimus/MMF for GVHD prophylaxis after HLA-identical related donor peripheral blood HCT in patients with hematologic malignancies (n = 150) using conditioning with 2 Gy total body irradiation (TBI) for patients with a preceding (within 6 months) planned autologous HCT (n = 50) or combined with 90 mg/m fludarabine for those without recent autologous HCT (n = 100). Oral tacrolimus was given from days -3 to 56 (tapered by day +180 if no GVHD). Oral MMF was given from days 0 to 27. Patient median age was 57 (range, 20 to 74) years. The cumulative incidences (CI) of day 100 grade II to IV and III to IV acute GVHD were 27% and 4%, respectively. With median follow-up of 10.3 (range, 3.1 to 14.5) years, the 5-year CI of chronic extensive GVHD was 48%. One-year and 5-year estimates of nonrelapse mortality, relapse/progression, survival, and progression-free survival were 9% and 13%, 35% and 50%, 73% and 53%, and 56% and 37%, respectively. GVHD prophylaxis with tacrolimus/MMF resulted in a low risk of acute GVHD and compared favorably with results from a concurrent trial using CSP/MMF. A randomized phase III trial to investigate tacrolimus/MMF versus CSP/MMF in nonmyeloablative HCT is warranted.
使用环孢素（CSP）和霉酚酸酯（MMF）进行移植后免疫抑制，对来自 HLA 相同的相关供者进行非清髓性异基因造血细胞移植（HCT），是治疗血液系统癌症的有效方法。然而，移植物抗宿主病（GVHD）仍然是发病和死亡的主要原因。初步数据表明，与非清髓性 HCT 后使用 CSP/MMF 的历史经验相比，他克莫司/MMF 的急性 GVHD 发病率更低。在一项 II 期多中心试验中，我们评估了他克莫司/MMF 对血液系统恶性肿瘤患者（n = 150）进行 HLA 相同的相关供者外周血 HCT 后预防 GVHD 的效果，对于之前（6 个月内）计划进行自体 HCT 的患者（n = 50），使用 2 Gy 全身照射（TBI）进行预处理，对于近期未进行自体 HCT 的患者（n = 100），则联合 90 mg/m²氟达拉滨进行预处理。口服他克莫司从第 -3 天至第 56 天给药（如果没有 GVHD，则在第 +180 天逐渐减量）。口服 MMF 从第 0 天至第 27 天给药。患者中位年龄为 57 岁（范围 20 至 74 岁）。第 100 天 II 至 IV 级和 III 至 IV 级急性 GVHD 的累积发生率（CI）分别为 27%和 4%。中位随访 10.3 年（范围 3.1 至 14.5 年），慢性广泛性 GVHD 的 5 年 CI 为 48%。非复发死亡率、复发/进展、生存率和无进展生存率的 1 年和 5 年估计值分别为 9%和 13%、35%和 50%、73%和 53%、56%和 37%。他克莫司/MMF 预防 GVHD 导致急性 GVHD 风险较低，与同期使用 CSP/MMF 的试验结果相比具有优势。有必要进行一项随机 III 期试验，以研究他克莫司/MMF 与 CSP/MMF 在非清髓性 HCT 中的疗效。
