Background Recent ECIL-guidelines recommend a quantitative PCR (qPCR) guided pre-emptive treatment approach to toxoplasmosis in seropositive recipients of allogeneic hematopoietic cell transplantation (allo-HCT). While qPCR might serve as a sensitive tool for early Toxoplasma detection, its role in treatment follow-up remains unknown. Methods We analyzed the qPCR kinetics of allo-HCT recipients experiencing either Toxoplasma infection (TI, n=71) or disease (TD, n=14) in relation to different parameters. We included 85 patients with available qPCR values expressed as quantitative cycle (Cq) from four large hematological centers from 2009 to 2023, and kinetic analysis was performed in a selection of 74 patients screened at least weekly with blood qPCR. Day 0 (D0) was the day of anti-Toxoplasma treatment start or (when untreated) day of diagnosis. Results Time to qPCR negativity was inversely proportional to the Cq value at D0 (p=0.0063). Not reaching negativity at D10 was associated with a significantly higher mortality at D30 (p=0.023). Patients with a high D0-parasitic load and patients with TD showed slower clearance (p<0.001, p=0.032). Time to negativity was not significantly different for patients started on prophylactic vs curative doses as first-line treatment regimen (p=0.16). Conclusions This study underscores the predictive value of qPCR kinetics monitoring in allo-HCT patients with toxoplasmosis. With the aforementioned risk factors, clinicians can identify patients at high-risk for worse outcome. Our results support to consider a therapeutic change or reinforcement if the parasitic load does not decrease after 10 days, supplementing existing clinical guidelines.

中文翻译：

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弓形虫 qPCR 动力学指导同种异体造血干细胞移植后弓形虫病的抢先治疗


背景 最近的 ECIL 指南推荐了对同种异体造血细胞移植 （allo-HCT） 血清阳性受者的弓形虫病采用定量 PCR （qPCR） 指导的先发制人治疗方法。虽然 qPCR 可能作为早期弓形虫检测的敏感工具，但其在治疗随访中的作用仍然未知。方法 我们分析了与不同参数相关的经历弓形虫感染 （TI， n=71） 或疾病 （TD， n=14） 的同种异体 HCT 受体的 qPCR 动力学。我们纳入了 2009 年至 2023 年来自四个大型血液学中心的 85 名具有可用 qPCR 值（以定量循环 （Cq） 表示）的患者，并在至少每周使用血液 qPCR 筛查的 74 名患者中进行了动力学分析。第 0 天 （D0） 是抗弓形虫治疗开始的日期或（未经治疗时）诊断的日期。结果 qPCR 阴性时间与 D0 的 Cq 值成反比 （p=0.0063）。在 D10 时未达到阴性与 D30 时死亡率显着升高相关 （p=0.023）。高 D0 寄生负荷患者和 TD 患者清除速度较慢 （p<0.001，p=0.032）。对于开始以预防剂量与治愈剂量作为一线治疗方案的患者，阴性时间没有显著差异 （p=0.16）。结论 本研究强调了 qPCR 动力学监测对同种异体 HCT 弓形虫病患者的预测价值。通过上述风险因素，临床医生可以识别出预后更差的高风险患者。如果寄生负荷在 10 天后没有减少，我们的结果支持考虑治疗改变或加强治疗，以补充现有的临床指南。