Oral valganciclovir as preemptive therapy for cytomegalovirus infection post allogeneic stem cell transplantation

Antiviral compounds including ganciclovir, foscarnet, and cidofovir are routinely used in the treatment of cytomegalovirus (CMV) infection and disease; however, these agents have a poor oral bioavailability and have the inconvenience and expense of intravenous administration. AIM OF THE STUDY: To evaluate the safety and efficacy of oral valganciclovir (VGCV) for preemptive treatment of CMV reactivation in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: We treated 15 patients receiving allogeneic HSCT from related (n=9) or unrelated (n=6) donors. In all patients, either the donor, host, or both were CMV Ig G positive pretransplant. Indication for therapy was preemptive treatment of CMV infection defined as one or two consecutive positive tests of pp65 antigenemia assay or CMV-polymerase chain reaction (PCR). VGCV was administered orally in a dosage of 900 mg b.i.d. for 2 weeks, followed by 450 mg b.i.d. for 2 additional weeks. RESULTS: Patients developed a positive CMV-PCR after a median of 52 days (range 37-427) post HSCT and a positive pp65 antigenemia after a median time of 74 days (range 37-427) post HSCT. Preemptive treatment with VGCV was started a median time of 56 days (range 37-429) after transplant. In all, 11 patients (73%) completed the 28 days of therapy with VGCV. All patients showed a complete clearance of the virus. The median time to achieve a negative CMV-PCR was 6 days (range 4-18). A relapse of CMV infection after VGCV preemptive therapy occurred in 6 patients (40%). No patient developed early or late CMV disease. Six patients (40%) presented hematological toxicity including neutropenia and/or thrombocytopenia that required drug discontinuation in 4 cases. CONCLUSION: VGCV administered as preemptive therapy for CMV infection in patients receiving an allogeneic HSCT showed promise for treating this frequent complication. Prospective randomized studies in this setting are mandatory to yield more definitive results.     

A randomized trial of preemptive therapy for prevention of cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation

We studied the efficacy of two different doses of ganciclovir to prevent cytomegalovirus (CMV) disease in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. We randomly assigned allogeneic HSCT recipients who had CMV infection to receive preemptive ganciclovir therapy with or without induction phase (5 mg/kg twice daily for 1 week). Thirty-two and thirty-six patients were randomized to the standard and the low-dose therapy group, respectively. The median time to CMV antigenemia or viremia clearance was 7 days (3–25 days) in the standard therapy group versus 11 days (3–69 days) in the low-dose therapy group (P = 0.540). The incidence of CMV disease was similar between the two groups (P = 0.366). The Kaplan–Meier estimate of event-free survival by day 180 after HSCT was 76.2% in the standard therapy group versus 66.7% in the low-dose therapy group (P = 0.590). Severe neutropenia (<0.5 × 10⁹/L) was observed in four (12.5%) patients in the standard therapy group versus two (5.6%) patients in the low-dose therapy group (P = 0.314). This study suggests that a low-dose ganciclovir preemptive therapy can be as effective as the standard-dose ganciclovir preemptive therapy for the prevention of CMV disease in allogeneic HSCT recipients.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

抢先治疗异基因造血干细胞移植后巨细胞病毒感染的临床分析

目的 回顾性分析抢先治疗异基因造血干细胞移植(allo-HSCT)后巨细胞病毒(CMV)感染的临床意义.方法 allo-HSCT治疗的患者103例,采用荧光定量PCR法监测CMV-DNA,并根据其结果抢先治疗CMV相关疾病,分析抢先治疗对于阻止CMV血症发展为CMV相关疾病的意义.结果 103例患者中检测出63例次(51例)CMV-DNA阳性,CMV血症发生率为49.5%,经抢先治疗19例发生CMV相关疾病,发生率为18.4%.60例次CMV血症经更昔洛韦和(或)膦甲酸治疗转阴,1例不可评价疗效,治疗的总有效率为96.8%(60/62).CMV相关疾病的治疗总有效率为89.5%(17/19),2例患者因CMV相关肺炎伴急性GVHD而死亡,CMV相关疾病的直接死亡率为1.9%(2/103).结论 在不进行预防性治疗的前提下,CMV血症和CMV相关疾病发生率未见升高.抢先治疗能有效阻止大部分CMV血症患者发病,并能有效控制CMV相关疾病的进展.     

Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation

Cytomegalovirus (CMV) disease remains a major cause of morbidity following allogeneic stem cell transplantation (SCT). In a prospective randomized trial, we tested prophylactic therapy with ganciclovir or acyclovir for patients at high risk of disease. Ninety-one CMV seropositive recipients of related (n = 53) and unrelated (n = 38) donor transplants were enrolled. All patients received intravenous (i.v.) ganciclovir 5 mg/kg every 12 h days -7 to -2, followed by acyclovir 10 mg/kg i.v. every 8 h from day -1 until neutrophil engraftment. Patients were then randomly assigned to either ganciclovir (n = 45) or acyclovir (n = 46) until day 100 post transplant. Any degree of antigenemia was treated with ganciclovir 5 mg/kg i.v. twice a day for 2 weeks, followed by 5 mg/kg i.v. each weekday for 6 weeks. At day 100, the cumulative incidence of antigenemia was 31% (95% CI 17-45%) for ganciclovir and 41% (95% CI 26-56%) (P = 0.22) for acyclovir prophylaxis, respectively. The assigned prophylaxis cohort did not predict for CMV antigenemia. The cumulative incidence of CMV disease at 12 months was 13% (95% CI 3-23%) and 17% (95% CI 6-28%) (P = 0.59) for the ganciclovir- and acyclovir-treated groups, respectively. An absolute neutrophil count (ANC) 相似文献   

Dose-adjusted preemptive therapy for cytomegalovirus disease based on real-time polymerase chain reaction after allogeneic hematopoietic stem cell transplantation

We have prospectively evaluated the efficacy of real-time PCR-guided preemptive therapy for CMV diseases in allogeneic hematopoietic stem cell transplant recipients with grades II-IV acute GVHD. The dose of ganciclovir was adjusted according to the viral load determined by real-time polymerase chain reaction (PCR). On detecting CMV reactivation in the plasma, ganciclovir was initiated at a dose of 5 mg/kg body weight once daily, and the dose was increased to twice daily if viral load continued to increase after initiating ganciclovir. In 39 evaluable patients, CMV reactivation assessed by real-time PCR became positive in 30 (77%). One developed CMV gastroenteritis before PCR became positive. Thus the remaining 29 patients were treated preemptively with ganciclovir. The dose of ganciclovir was increased in 12 patients (41%) of preemptively treated patients for increasing viral load. CMV diseases were diagnosed in two patients (one gastroenteritis and one retinitis), and late CMV disease was diagnosed in one patient (gastritis). The treatment was generally well-tolerated, but three patients (10%) developed neutropenia (neutrophil count less than 1.0 x 10(9)/l). In conclusion, real-time PCR-guided preemptive therapy with decreased dose of ganciclovir is feasible and does not increase the frequency of CMV diseases if the dose is adjusted according to the viral load.     

Reduced dose of foscarnet as preemptive therapy for cytomegalovirus infection following reduced-intensity cord blood transplantation

Although foscarnet is a promising alternative for the treatment of cytomegalovirus (CMV) infection, its toxicity can be significant in patients with advanced age. We retrospectively reviewed medical records of 123 patients (median age of 55; range, 17-79) who received reduced-intensity cord blood transplantation (RI-CBT). Patients preemptively received reduced-dose foscarnet 30 mg/kg twice daily when CMV antigenemia exceeded 10/50,000. Sixty-three patients developed CMV antigenemia on a median of day 34, and 29 received foscarnet preemptively. The median level of CMV antigenemia at the initiation of foscarnet was 30. Median duration of foscarnet administration was 24 days. Adverse effects included electrolyte abnormalities (n=19), renal impairment (n=13), and skin eruption requiring discontinuation of foscarnet (n=1). Preemptive therapy of foscarnet was completed in 18 patients. Seven patients died during foscarnet use without developing CMV disease. The remaining 3 developed CMV enterocolitis 5, 14, and 17 days after initiation of foscarnet. All of them were successfully treated with ganciclovir or foscarnet. Reduced dose of foscarnet is beneficial to control CMV reactivation following RI-CBT; however, it has considerable toxicities in RI-CBT recipients with advanced age. Further studies are warranted to minimize toxicities and identify optimal dosages.     

A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir (5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log10 higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo.     

Ganciclovir预防异基因造血干细胞移植后巨细胞病毒感染

目的 :评价Ganciclovir在异基因造血干细胞移植 (allo HSCT)后预防巨细胞病毒 (CMV)感染的效果。方法 :观察allo HSCT患者 46例 ,全部病例均系移植前受者和 (或 )供者的CMV IgG阳性 ,分为预防组 2 4例 ,对照组 2 2例。allo HSCT后当患者血中性粒细胞 >1.0× 10 9/L时 ,预防组开始用GCV 10mg·kg-1·d-1,分两次静滴 ,连续 5d ;然后改为 5mg·kg-1·d-1,每周用 5d ,直至 +10 0d。对照组未预防性使用GCV。结果 :在 +10 0d内 ,预防组和对照组的CMV感染率分别为 8% (2 / 2 4)、32 % (7/ 2 2 ) ,P <0 .0 5 ;CMV病发病率分别为 0 %、18% (4 / 2 2 ) ,P <0 .0 5。两组患者在 +10 0d和 +180d内的死亡率分别为 4% (1/ 2 4)和 5 % (1/ 2 2 ) ,P >0 .0 5 ;12 .5 % (3/ 2 4)和 9% (2 / 2 2 ) ,P >0 .0 5。预防组的死因分别为并发细菌和真菌感染、CMV间质性肺炎或原发病复发 ;对照组的死因均是CMV间质性肺炎。结论 :allo HSCT后预防性使用GCV能明显抑制CMV感染 ,减少CMV病发病率。GCV的主要毒副作用是导致中性粒细胞减少 ,使患者继发感染甚至死亡的机率增加。GCV预防性使用的最佳剂量、用药方案及持续时间均有待进一步探讨     

Significance of qualitative PCR detection method for preemptive therapy of cytomegalovirus infection in patients after allogeneic hematopoietic stem cell transplantation -- single-centre experience

Both early cytomegalovirus (CMV) monitoring and prophylactic antiviral therapy can decrease clinical complications or can prevent them in patients after allogeneic hematopoietic stem cell transplantation (HSCT). Presented paper summarizes experiences with using regular monitoring of reactivation of CMV after allogeneic HSCT by qualitative polymerase chain reaction (PCR) method to prevent the development of symptomatic CMV disease. Samples of peripheral blood leukocytes (PBL) in 71 patients were monitored. Because of retransplantation in two patients, 73 transplantations, each followed by the monitoring, were performed. Patients were monitored weekly after the transplantation for CMV DNA-emia in PBL. An episode of CMV infection representing an indication for preemptive ganciclovir (GCV) or foscarnet (FOS) therapy was defined as two consecutive positive PCR results in 4-7 days. Median time of monitoring was 313 days. The CMV infection was found in 28/73 monitorings (38.4%) and always was followed by preemptive therapy. One recurrence of CMV infection was observed in 4/28 (14.3%) monitorings and two recurrences in 1/28 (3.6%) monitorings. Presented approach resulted in complete prevention of overt CMV disease and this study enable to show that qualitative PCR method for determination of incipient CMV infection followed by preemptive therapy is suitable for preventing patients after allogeneic transplantation from CMV disease.