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第 4 天采集粒细胞集落刺激因子动员的 HLA 匹配同胞供体外周血移植物,并未显示慢性移植物抗宿主病或复发率的长期增加。

Day 4 collection of granulocyte colony-stimulating factor-mobilized HLA-matched sibling donor peripheral blood allografts demonstrates no long-term increase in chronic graft-versus-host disease or relapse rates.

机构信息

Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.

Biostatistics Shared Resources, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.

出版信息

Cytotherapy. 2023 Apr;25(4):423-431. doi: 10.1016/j.jcyt.2022.11.004. Epub 2023 Jan 21.

Abstract

BACKGROUND AIMS

In a previous pilot study of HLA-matched sibling donor hematopoietic cell transplantation (HCT), the authors determined the feasibility of day 4 versus day 5 granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) collection compared with a historical cohort. Given identified differences in the PBSC product (day 4 cohort with significantly lower infused total nucleated, mononuclear and CD3 cells compared with other collection cohorts), the authors performed a follow-up study to determine long-term post-HCT outcomes, including detailed characterization of chronic graft-versus-host disease (GVHD).

METHODS

This was a prospective observational study, and the authors collected data on chronic GVHD, staging, sites of involvement and treatments. Performance status, incidence of relapse, overall survival and duration of immunosuppressive therapy (IST) were also evaluated. Data were examined retrospectively. To account for differences in length of follow-up among cohorts, the authors also determined performance status and chronic GVHD staging, sites and treatment at 2 years post-HCT.

RESULTS

At 2 years post-HCT, the overall survival rate was 71.7% in the day 4 cohort compared with 61.5%, 52% and 56% in the day 5, 2-day and historical cohorts, respectively (P = 0.283). The cumulative incidence of chronic GVHD was 65.2% in the day 4 cohort versus 46.4% in the day 5 cohort, 51.1% in the 2-day cohort and 65% in the historical cohort (P = 0.26). There was no significant difference in the maximum overall stage of chronic GVHD (P = 0.513), median number of sites involved (P = 0.401) or cumulative incidence of discontinuation of IST (P = 0.32). Death from chronic GVHD was less common in the day 4 and day 5 cohorts compared with the 2-day and historical cohorts, though this did not reach statistical significance.

CONCLUSIONS

The authors' preliminary results demonstrated that collection of allogeneic matched sibling donor PBSCs on day 4 of G-CSF was feasible, reduced donor exposure to growth factor and was associated with an initial cost savings. Importantly, the authors now demonstrate that transplantation of day 4 mobilized PBSCs is not associated with any adverse outcomes post-HCT, including late effects such as chronic GVHD. Further investigation of donor G-CSF collection algorithms is merited in other HCT settings, including unrelated and mismatched related donors.

摘要

背景目的

在之前一项关于 HLA 匹配的同胞供者造血细胞移植(HCT)的试点研究中,作者确定了与历史队列相比,第 4 天与第 5 天粒细胞集落刺激因子(G-CSF)动员外周血干细胞(PBSC)采集的可行性。鉴于 PBSC 产物中存在差异(第 4 天采集组与其他采集组相比,输注的总核细胞、单核细胞和 CD3 细胞明显较低),作者进行了一项后续研究,以确定 HCT 后的长期结果,包括慢性移植物抗宿主病(GVHD)的详细特征。

方法

这是一项前瞻性观察性研究,作者收集了慢性 GVHD、分期、受累部位和治疗的数据。还评估了表现状态、复发率、总生存率和免疫抑制治疗(IST)的持续时间。数据是回顾性检查的。为了考虑队列之间随访时间的差异,作者还确定了 HCT 后 2 年时的表现状态和慢性 GVHD 分期、受累部位和治疗。

结果

HCT 后 2 年时,第 4 天采集组的总生存率为 71.7%,而第 5 天、2 天和历史队列分别为 61.5%、52%和 56%(P=0.283)。第 4 天采集组慢性 GVHD 的累积发生率为 65.2%,第 5 天采集组为 46.4%,2 天采集组为 51.1%,历史队列为 65%(P=0.26)。慢性 GVHD 的最大总体分期无显著差异(P=0.513),受累部位中位数无显著差异(P=0.401),IST 停药的累积发生率无显著差异(P=0.32)。与 2 天和历史队列相比,第 4 天和第 5 天采集组死于慢性 GVHD 的情况较少,但这并未达到统计学意义。

结论

作者的初步结果表明,在 G-CSF 的第 4 天采集异基因匹配的同胞供者 PBSC 是可行的,减少了供者接触生长因子的机会,并与初始成本节约相关。重要的是,作者现在证明,HCT 后第 4 天采集的 PBSC 移植与任何不良后果无关,包括慢性 GVHD 等晚期影响。在其他 HCT 环境中,包括无关和不匹配的亲缘供者,进一步研究供者 G-CSF 采集算法是值得的。

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