Charité Universitätsmedizin Berlin, Berlin, Germany.
EBMT Statistical Unit, Paris, France.
Haematologica. 2020 Jul;105(7):1977-1983. doi: 10.3324/haematol.2019.228668. Epub 2019 Oct 10.
Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation (alloSCT) derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft--host disease (GvHD). In a clinical pilot trial, peri-transplant uric acid depletion reduced acute GvHD incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with alloSCT outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling alloSCT from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 alloSCT recipients. There were no significant differences in terms of baseline comorbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from the remaining in terms of acute GvHD grades II-IV incidence (Hazard ratio [HR] 1.5, 95% Confidence interval [CI]: 1.0-2.4, =0.08). However, they had significantly shorter overall survival (HR 2.8, 95% CI: 1.7-4.7, <0.0001) and progression free survival (HR 1.6, 95% CI: 1.1-2.4, =0.025). Non-relapse mortality was significantly increased in alloSCT recipients with high uric acid levels (HR 2.7, 95% CI: 1.4-5.0, =0.003). Finally, the incidence of relapse after alloSCT was increased in patients with higher uric acid levels (HR 1.6, 95% CI: 1.0-2.5, =0.04). We conclude that high uric acid levels before the start of conditioning correlate with increased mortality after alloSCT.
尿酸是导致炎症的危险信号。其与异基因造血干细胞移植（alloSCT）的相关性源自临床前模型，其中尿酸的耗竭导致存活率提高和移植物抗宿主病（GvHD）减少。在一项临床试点试验中，移植前尿酸耗竭降低了急性 GvHD 的发生率。这项前瞻性国际多中心研究旨在探讨预处理前尿酸血清水平与 alloSCT 结果的关系。我们纳入了接受来自外周血的首次匹配同胞 alloSCT 的急性白血病、淋巴瘤或骨髓增生异常综合征患者，无论其预处理情况如何。我们使用特定原因 Cox 模型进行单变量和多变量分析，比较高尿酸和低尿酸水平患者的结局。来自 10 个国家的 20 个中心报告了 366 例 alloSCT 受者的数据。高尿酸组和低尿酸组之间的基线合并症和疾病分期无显著差异。在预处理前测量的尿酸水平高于中位数的患者，在急性 GvHD Ⅱ-Ⅳ级发生率方面与其余患者无显著差异（危险比[HR] 1.5，95%置信区间[CI]：1.0-2.4，=0.08）。然而，他们的总生存（HR 2.8，95% CI：1.7-4.7，<0.0001）和无进展生存（HR 1.6，95% CI：1.1-2.4，=0.025）明显缩短。高尿酸水平的 alloSCT 受者的非复发死亡率显著增加（HR 2.7，95% CI：1.4-5.0，=0.003）。最后，高尿酸水平患者 alloSCT 后复发的发生率增加（HR 1.6，95% CI：1.0-2.5，=0.04）。我们得出结论，预处理前尿酸水平升高与 alloSCT 后死亡率增加相关。
