Fred Hutchinson Cancer Research Center, Seattle, WA.
Department of Medicine, University of Washington, Seattle, WA.
Blood Adv. 2020 Feb 25;4(4):617-628. doi: 10.1182/bloodadvances.2019000802.
BK polyomavirus (BKPyV) has been associated with hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (HCT), but the natural history of HC and factors associated with the clinical course are incompletely understood. We retrospectively analyzed allogeneic HCT patients transplanted from 2007-2017 who presented after platelet engraftment or after day 28 post-HCT with BKPyV-associated HC (BKPyV-HC), which was defined as a positive urine BKPyV PCR, ≥1 plasma BKPyV viral load result, and macroscopic hematuria (Bedi grade ≥2). Factors associated with resolution of macroscopic hematuria and resolution of all cystitis symptoms within 90 days after HC diagnosis were investigated in multivariable models. In 128 patients with BKPyV-HC, the median times from diagnosis to resolution of all symptoms, macroscopic hematuria, and urinary clots (present in 55% [71/128]) were 24 days (15-44), 17 days (10-30), and 14 days (5-26), respectively. Ninety percent of patients had BKPyV viremia at the onset of HC with a median viral load of 1850 copies/mL (interquartile range, 240-8550). In multivariable models, high plasma viral load (≥10 000 copies/mL) and cytopenias at the beginning of BKPyV-HC were significantly associated with longer macroscopic hematuria and cystitis symptoms. Use of cidofovir was not associated with shorter duration of illness. In conclusion, BKPyV-HC after allogeneic HCT is characterized by prolonged and severe symptoms and requires improved management strategies. High-grade viremia and cytopenias were associated with a longer duration of BKPyV-associated HC. Accurate descriptions of disease and factors associated with prolonged recovery will inform end points of future clinical trials.
BK 多瘤病毒(BKPyV)与异基因造血细胞移植(HCT)后的出血性膀胱炎(HC)有关,但 HC 的自然病史和与临床病程相关的因素尚不完全清楚。我们回顾性分析了 2007 年至 2017 年间接受异基因 HCT 的患者,这些患者在血小板植入后或 HCT 后第 28 天出现 BKPyV 相关 HC(BKPyV-HC),其定义为尿 BKPyV PCR 阳性、≥1 次血浆 BKPyV 病毒载量结果和肉眼血尿(Bedi 分级≥2)。在多变量模型中,研究了与 HC 诊断后 90 天内肉眼血尿消退和所有膀胱炎症状消退相关的因素。在 128 例 BKPyV-HC 患者中,从诊断到所有症状、肉眼血尿和尿血块(55%[71/128]存在)消退的中位时间分别为 24 天(15-44)、17 天(10-30)和 14 天(5-26)。90%的患者在 HC 发病时存在 BKPyV 血症,中位病毒载量为 1850 拷贝/ml(四分位间距,240-8550)。在多变量模型中,高血浆病毒载量(≥10000 拷贝/ml)和 BKPyV-HC 开始时的细胞减少与肉眼血尿和膀胱炎症状持续时间较长显著相关。使用更昔洛韦与疾病持续时间缩短无关。总之,异基因 HCT 后的 BKPyV-HC 表现为症状延长和严重,需要改进管理策略。高病毒血症和细胞减少与 BKPyV 相关 HC 持续时间较长相关。准确描述疾病和与恢复时间延长相关的因素将为未来临床试验的终点提供信息。