Bedi A, Miller C B, Hanson J L, Goodman S, Ambinder R F, Charache P, Arthur R R, Jones R J
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Clin Oncol. 1995 May;13(5):1103-9. doi: 10.1200/JCO.1995.13.5.1103.
Hemorrhagic cystitis (HC) after bone marrow transplantation (BMT) has been ascribed to cyclophosphamide metabolites. HC has also been associated with excretion of the BK type of polyomavirus. The relative contributions of cyclophosphamide metabolites and BK virus in the development of HC following BMT are unknown.
We conducted a randomized trial to compare mesna with forced diuresis for prophylaxis against HC in 147 BMT recipients. We studied the association of BK virus with HC in 95 consecutive BMT recipients by prospectively monitoring urinary excretion of BK virus using polymerase chain reaction amplification of viral gene sequences.
HC occurred in 37 of 147 (25.2%) transplant recipients. The incidence of HC was similar in patients given mesna (26.8%, 19 of 71) or forced diuresis (23.7%, 18 of 76), and in recipients of allogeneic (27.2%, 18 of 64) or autologous marrow (22.9%, 19 of 83). The incidence of HC was unrelated to primary disease, preparative regimen, or occurrence of graft-versus-host disease (GVHD). Excretion of BK virus was demonstrated in 50 of 95 patients (52.6%); 38 patients (40%) had persistent BK viruria (> or = two consecutive positive samples). HC occurred in 19 of 38 patients (50%) with persistent BK viruria, in one of 12 (8.3%) with only a single urine sample positive for BK virus, and in none of 45 who did not excrete BK virus (P < .0001). Shedding of BK virus also had a strong temporal correlation with onset of HC (r = .95).
Mesna and forced diuresis are equally effective in abrogating the urothelial toxicity of preparative regimens for BMT. Since HC after BMT is virtually always associated with persistent BK viruria, strategies aimed at the prevention or elimination of viruria in BK seropositive recipients are warranted.
骨髓移植（BMT）后出血性膀胱炎（HC）被认为与环磷酰胺代谢产物有关。HC也与BK型多瘤病毒的排泄有关。环磷酰胺代谢产物和BK病毒在BMT后HC发生过程中的相对作用尚不清楚。
我们进行了一项随机试验，比较美司钠与强制利尿在147例BMT受者中预防HC的效果。我们通过使用病毒基因序列的聚合酶链反应扩增前瞻性监测BK病毒的尿排泄情况，研究了95例连续BMT受者中BK病毒与HC的关联。
147例移植受者中有37例（25.2%）发生HC。接受美司钠治疗的患者（26.8%，71例中的19例）或强制利尿治疗的患者（23.7%，76例中的18例），以及接受异基因（27.2%，64例中的18例）或自体骨髓移植的患者（22.9%，83例中的19例），HC的发生率相似。HC的发生率与原发疾病、预处理方案或移植物抗宿主病（GVHD）的发生无关。95例患者中有50例（52.6%）检测到BK病毒排泄；38例患者（40%）有持续性BK病毒尿（连续两个或更多阳性样本）。38例持续性BK病毒尿患者中有19例（50%）发生HC，12例仅一份尿样BK病毒阳性的患者中有1例（8.3%）发生HC，45例未排泄BK病毒的患者中无一例发生HC（P<0.0001）。BK病毒的排出与HC的发生也有很强的时间相关性（r=0.95）。
美司钠和强制利尿在消除BMT预处理方案对尿路上皮的毒性方面同样有效。由于BMT后的HC几乎总是与持续性BK病毒尿相关，因此有必要采取旨在预防或消除BK血清阳性受者病毒尿的策略。
