接受移植后环磷酰胺治疗的HLA匹配和HLA单倍型相同移植后的可比复合终点。
Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide.
作者信息
McCurdy Shannon R, Kasamon Yvette L, Kanakry Christopher G, Bolaños-Meade Javier, Tsai Hua-Ling, Showel Margaret M, Kanakry Jennifer A, Symons Heather J, Gojo Ivana, Smith B Douglas, Bettinotti Maria P, Matsui William H, Dezern Amy E, Huff Carol Ann, Borrello Ivan, Pratz Keith W, Gladstone Douglas E, Swinnen Lode J, Brodsky Robert A, Levis Mark J, Ambinder Richard F, Fuchs Ephraim J, Rosner Gary L, Jones Richard J, Luznik Leo
机构信息
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Biostatistics & Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
出版信息
Haematologica. 2017 Feb;102(2):391-400. doi: 10.3324/haematol.2016.144139. Epub 2016 Oct 20.
Composite endpoints that not only encompass mortality and relapse, but other critical post-transplant events such as graft-versus-host disease, are being increasingly utilized to quantify survival without significant morbidity after allogeneic blood or marrow transplantation. High-dose, post-transplantation cyclophosphamide reduces severe graft-versus-host disease with allogeneic marrow transplantation, making composite endpoints after this management particularly interesting. We retrospectively analyzed 684 adults with hematologic malignancies who received T-cell-replete bone marrow grafts and cyclophosphamide after myeloablative HLA-matched related (n=192) or unrelated (n=120), or non-myeloablative HLA-haploidentical (n=372) donor transplantation. The median follow up was 4 (range, 0.02-11.4) years. Graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without grade III-IV acute graft-versus-host disease, chronic graft-versus-host disease requiring systemic treatment, relapse, or death. Chronic graft-versus-host disease-free, relapse-free survival was defined as the time after transplantation without moderate or severe chronic graft-versus-host disease, relapse, or death. One-year graft-versus-host disease-free, relapse-free survival and chronic graft-versus-host disease-free, relapse-free survival estimates were, respectively, 47% (95% CI: 41-55%) and 53% (95% CI: 46-61%) after myeloablative HLA-matched related, 42% (95% CI: 34-52%) and 52% (95% CI: 44-62%) after myeloablative HLA-matched unrelated, and 45% (95% CI: 40-50%) and 50% (95% CI: 45-55%) after non-myeloablative HLA-haploidentical donor transplantation. In multivariable models, there were no differences in graft-versus-host disease-free, or chronic graft-versus-host disease-free, relapse-free survival after either myeloablative HLA-matched unrelated or non-myeloablative HLA-haploidentical, compared with myeloablative HLA-matched related donor transplantation. Although limited by inclusion of dissimilar cohorts, we found that post-transplantation cyclophosphamide-based platforms yield comparable composite endpoints across conditioning intensity, donor type, and HLA match.
复合终点不仅包括死亡率和复发率，还涵盖其他移植后关键事件，如移植物抗宿主病，目前越来越多地用于量化异基因血液或骨髓移植后无显著发病情况下的生存率。高剂量移植后环磷酰胺可降低异基因骨髓移植后的严重移植物抗宿主病，使得这种治疗方式后的复合终点特别值得关注。我们回顾性分析了684例患有血液系统恶性肿瘤的成年人，他们在接受清髓性 HLA 匹配的相关供者（n = 192）或无关供者（n = 120）移植，或非清髓性 HLA 单倍型相合供者（n = 372）移植后接受了富含 T 细胞的骨髓移植及环磷酰胺治疗。中位随访时间为4（范围：0.02 - 11.4）年。无移植物抗宿主病、无复发生存期定义为移植后无 III - IV 级急性移植物抗宿主病、无需全身治疗的慢性移植物抗宿主病、复发或死亡的时间。无慢性移植物抗宿主病、无复发生存期定义为移植后无中度或重度慢性移植物抗宿主病、复发或死亡的时间。清髓性 HLA 匹配的相关供者移植后1年无移植物抗宿主病、无复发生存率及无慢性移植物抗宿主病、无复发生存率估计值分别为47%（95%CI：41 - 55%）和53%（95%CI：46 - 61%），清髓性 HLA 匹配的无关供者移植后分别为42%（95%CI：34 - 52%）和52%（95%CI：44 - 62%），非清髓性 HLA 单倍型相合供者移植后分别为45%（95%CI：40 - 50%）和50%（95%CI：45 - 55%）。在多变量模型中，与清髓性 HLA 匹配的相关供者移植相比，清髓性 HLA 匹配的无关供者移植或非清髓性 HLA 单倍型相合供者移植后的无移植物抗宿主病或无慢性移植物抗宿主病、无复发生存率并无差异。尽管因纳入不同队列而存在局限性，但我们发现基于移植后环磷酰胺的治疗方案在预处理强度、供者类型和 HLA 匹配方面产生了可比的复合终点。
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