The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, Georgia.
Biol Blood Marrow Transplant. 2019 Nov;25(11):2211-2216. doi: 10.1016/j.bbmt.2019.06.017. Epub 2019 Jun 25.
Although myeloablative conditioning (MAC) before haploidentical donor transplant (HIDT) with post-transplant cyclophosphamide is being increasingly used, the optimal preparative regimen remains unclear. In our initial trial, the feasibility of HIDT following a MAC preparative regimen using fludarabine and 12 Gy of total-body irradiation was demonstrated in 30 patients. We now present long-term outcome results, including an additional 52 patients, now with 47 months (16 to 96) median follow-up. Median patient age was 42 (19 to 61) years. The most common diagnoses were acute myelogenous leukemia (51%) and acute lymphoblastic leukemia (33%), and 39% had a high/very high disease risk index (DRI). Engraftment was universal with no cases of primary or secondary graft failure. Grade 3 to 4 acute graft-versus-host disease (GVHD) and moderate to severe chronic GVHD occurred in 17% and 23%, respectively. Nonrelapse mortality (NRM) was 7% at 1 year and 13% at 4 years. Estimated 4-year overall survival (OS), disease-free survival, and cumulative incidence of relapse (CIR) were 67%, 60%, and 27%, respectively. CIR was significantly higher in patients with high/very high- versus low/intermediate-risk DRI (38% versus 20%, P= .032), which led to inferior 4-year OS (50% versus 77%, P = .001). Median time to systemic immunosuppressive therapy (IST) discontinuation was 7.8 months, with 84% of patients off IST at 2 years post-transplant. Current GHVD-free, relapse-free survival (CGRFS) at 2, 3, and 4 years was 60%, 57%, and 60%, respectively. This approach to MAC HIDT results in universal engraftment; low rates of NRM, infection, and clinically significant GVHD; and relatively rapid IST discontinuation, resulting in high rates of CGRFS and survival.
虽然在接受亲缘单倍体供者移植（HIDT）前采用清髓性预处理（MAC）方案并联合移植后环磷酰胺的治疗方案越来越多地被应用，但最佳的预处理方案仍不明确。在我们的初始试验中，在 30 例患者中证实了采用氟达拉滨和 12Gy 全身照射的 MAC 预处理方案进行 HIDT 的可行性。现在我们报告了长期结果，其中包括另外 52 例患者，目前中位随访时间为 47 个月（16 至 96 个月）。中位患者年龄为 42 岁（19 至 61 岁）。最常见的诊断是急性髓细胞性白血病（51%）和急性淋巴细胞性白血病（33%），39%的患者具有高/极高疾病风险指数（DRI）。所有患者均获得了普遍的移植物植入，无原发或继发移植物失败的病例。3 级至 4 级急性移植物抗宿主病（GVHD）和中重度慢性 GVHD 的发生率分别为 17%和 23%。1 年和 4 年时的非复发死亡率（NRM）分别为 7%和 13%。估计 4 年的总生存率（OS）、无病生存率和累积复发率（CIR）分别为 67%、60%和 27%。DRI 为高/极高风险与低/中风险的患者的 CIR 分别为 38%和 20%，差异具有统计学意义（P=.032），这导致了 4 年 OS 的降低（50%与 77%，P=.001）。停止全身免疫抑制治疗（IST）的中位时间为 7.8 个月，2 年后有 84%的患者停用 IST。2 年、3 年和 4 年时的无 GVHD、无复发生存率（CGRFS）分别为 60%、57%和 60%。这种 MAC-HIDT 治疗方法可实现普遍的移植物植入；NRM、感染和有临床意义的 GVHD 发生率低；以及 IST 快速停药，从而获得高 CGRFS 和生存率。
