Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan.
Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan.
Biol Blood Marrow Transplant. 2020 May;26(5):1005-1012. doi: 10.1016/j.bbmt.2020.01.025. Epub 2020 Feb 5.
Permanent impairment (PI) of vital organs is one of the transplantation-related health problems affecting the quality of life and morbidity even in patients who do not develop graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HCT), but no data are available on PI of multiple organs. This retrospective study aimed to estimate a novel composite endpoint of PI-free, relapse-free survival (PIRFS) in 164 allo-HCT recipients. We defined PI as >26% to 30% impairment of the whole person in 6 vital organs using the whole person impairment rating. Conventional GVHD-free/relapse-free survival (GRFS) and PIRFS at 5 years were 33.8% (95% confidence interval [CI], 26.5% to 41.3%) and 40.6% (95% CI, 32.6% to 48.4%), respectively. In the whole cohort, PIRFS was higher than GRFS at any time after allo-HCT. However, PIRFS was lower than GRFS after day 397 post-transplantation in patients who underwent umbilical cord blood transplantation (UCBT). In UCBT recipients, 5-year GRFS and PIRFS were 47.6% (95% CI, 34.3% to 59.7%) and 39.2% (95% CI, 26.6% to 51.5%), respectively. The cumulative incidence of PI after 5 years was 20.9% (95% CI, 13.7% to 29.0%) in patients surviving for ≥6 months without relapse. The multivariate analysis revealed that high disease risk (hazard ratio [HR], 1.91; 95% CI, 1.26 to 2.88; P < .01) and Karnofsky Performance Status score ≤90% at transplantation (HR, 1.73; 95% CI, 1.14 to 2.63; P = .01) were correlated with the lower PIRFS, whereas UCBT (HR, 2.35; 95% CI, 1.11 to 4.99; P = .03), grade III-IV acute GVHD by day 180 (HR, 3.59; 95% CI, 1.04 to 12.4; P = .04), and thrombotic microangiopathy by day 180 (HR, 2.74; 95% CI, 1.10 to 6.87; P = .03) were significantly correlated with a higher incidence of PI. More than 20% of long-term survivors had PI. Our data suggest that PIRFS is a useful endpoint for assessing long-term transplantation success from a different perspective than has been established previously.
永久性器官损伤 (PI) 是与异体造血干细胞移植 (allo-HCT) 后移植物抗宿主病 (GVHD) 无关的影响生活质量和发病率的移植相关健康问题之一，但目前尚无关于多器官 PI 的数据。这项回顾性研究旨在估计 164 例 allo-HCT 受者中新型多器官 PI 无、无复发生存 (PIRFS) 的复合终点。我们使用全人损伤评分将 6 个重要器官的全人损伤率 >26%至 30%定义为 PI。5 年时，常规 GVHD 无/无复发生存 (GRFS) 和 PIRFS 分别为 33.8%（95%CI，26.5%至 41.3%）和 40.6%（95%CI，32.6%至 48.4%）。在整个队列中，allo-HCT 后任何时间的 PIRFS 均高于 GRFS。然而，在接受脐带血移植 (UCBT) 的患者中，移植后第 397 天之后，PIRFS 低于 GRFS。在 UCBT 受者中，5 年 GRFS 和 PIRFS 分别为 47.6%（95%CI，34.3%至 59.7%）和 39.2%（95%CI，26.6%至 51.5%）。在≥6 个月无复发且存活的患者中，5 年后 PI 的累积发生率为 20.9%（95%CI，13.7%至 29.0%）。多变量分析显示，高疾病风险（风险比 [HR]，1.91；95%CI，1.26 至 2.88；P<.01）和移植时 Karnofsky 表现状态评分≤90%（HR，1.73；95%CI，1.14 至 2.63；P=.01）与较低的 PIRFS 相关，而 UCBT（HR，2.35；95%CI，1.11 至 4.99；P=.03）、第 180 天出现 III-IV 级急性 GVHD（HR，3.59；95%CI，1.04 至 12.4；P=.04）和第 180 天发生血栓性微血管病（HR，2.74；95%CI，1.10 至 6.87；P=.03）与更高的 PI 发生率显著相关。超过 20%的长期幸存者存在 PI。我们的数据表明，与之前建立的观点不同，PIRFS 是评估长期移植成功的一个有用的终点。
