Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Biol Blood Marrow Transplant. 2018 Feb;24(2):343-352. doi: 10.1016/j.bbmt.2017.10.023. Epub 2017 Oct 18.
Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30% (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%), respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to 13%). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%) and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with grade II aGVHD (P = .05 and P = .009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was .78 (95% CI, .54 to 1.13; P = .19) and .69 (95% CI, .48 to .98; P = .04). Higher nucleated cell graft dose was also associated with improved OS (HR, .88; 95% CI, .78 to 1.00; P = .05) and PFS (HR, .89; 95% CI, .79 to 1.0; P = .05) and decreased risk of grades III to IV aGVHD (subdistribution HR, .66; 95% CI, .46 to .96; P = .03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy.
与标准的移植物抗宿主病（GVHD）预防方案相比，T 细胞耗尽 HLA 单倍体（haplo）骨髓移植（BMT）后使用环磷酰胺（PTCy）可降低 III 至 IV 级急性（a）和慢性（c）GVHD 的风险，但维持相似的 II 级 aGVHD 发生率。鉴于轻度 GVHD 与 HLA 匹配 BMT 中的治疗失败减少相关，我们评估了 340 例血液恶性肿瘤患者在接受非清髓性haplo-BMT 后使用 PTCy、霉酚酸酯和他克莫司的 GVHD 对生存的风险因素和影响。第 100 天 II 级和 III 至 IV 级 aGVHD 的累积发生率分别为 30%（95%置信区间 [CI]，25%至 35%）和 2%（95%CI，1%至 4%）。cGVHD 的 1 年累积发生率为 10%（95%CI，7%至 13%）。在第 100 天的里程碑分析中，无 II 至 IV 级 aGVHD 的患者 4 年的总生存率（OS）和无进展生存率（PFS）的概率分别为 48%（95%CI，41%至 56%）和 39%（95%CI，32%至 47%），而有 II 级 aGVHD 的患者分别为 63%（95%CI，53%至 73%）和 59%（95%CI，50%至 71%）（P =.05 和 P =.009）。在多变量建模中，与从未经历过 GVHD 的患者相比，II 级 aGVHD 患者的 OS 和 PFS 风险比（HR）分别为.78（95%CI，.54 至 1.13；P =.19）和.69（95%CI，.48 至.98；P =.04）。更高的有核细胞移植物剂量也与 OS（HR，.88；95%CI，.78 至 1.00；P =.05）和 PFS（HR，.89；95%CI，.79 至 1.0；P =.05）的改善和 III 至 IV 级 aGVHD 风险的降低相关（亚分布 HR，.66；95%CI，.46 至.96；P =.03）。PTCy 可降低 III 至 IV 级 aGVHD 和 cGVHD，但保留相似的 II 级 aGVHD 发生率，后者的发展可改善 PFS。更高的有核细胞移植物剂量目标也可能改善 PTCy 非清髓性 haplo-BMT 后的生存。
