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.     

Preemptive therapy with ganciclovir 5 mg/kg once daily for cytomegalovirus infection after unrelated cord blood transplantation

The efficacy and safety of preemptive therapy using ganciclovir (GCV) 5 mg/kg once daily for CMV infection after unrelated cord blood transplantation (CBT) were studied. The initial preemptive therapy with GCV 5 mg/kg once daily led to resolution of CMV antigenemia in 25 of 34 patients (74%). In the remaining 9 patients (26%), antigenemia resolved after dose-escalation of GCV or change to foscarnet therapy. Recurrence of antigenemia was seen in 18 patients (53%). A total of 12 patients received the second preemptive therapy with GCV 5 mg/kg once daily, which led to resolution of antigenemia in 11 of 12 patients (92%). The remaining 1 patient (8%) required change to foscarnet therapy. None of 34 patients developed CMV disease. Neutropenia with an absolute neutrophil number of less than 1 and 0.5 x 10(9) per liter after GCV therapy occurred in 12 (35%) and 1 (3%) patients, respectively, after the initial therapy, and in 2 (17%) and 0 (0%) patients, respectively, after the second therapy. No patients developed neutropenic fever or secondary graft failure after GCV therapy. There were no deaths directly attributable to GCV therapy. The present study suggests that antigenemia-based preemptive strategy using GCV 5 mg/kg once daily is feasible and effective for CBT recipients.     

Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection

Recovery of cytomegalovirus (CMV)-specific T-cell-mediated immunity after allogeneic hematopoietic stem cell transplantation (SCT) is critical for protection against CMV disease. The study used fluorochrome-conjugated tetrameric complexes of HLA-A2 molecules loaded with the immunodominant NLVPMVATV (NLV) peptide derived from the CMV protein pp65 to quantify A2-NLV-specific CD8+ T cells in partially T-cell-depleted grafts administered to 27 HLA-A*0201+ patients and to monitor recovery of these T cells during the first 12 months after SCT. None of the 9 CMV-seronegative patients became infected with CMV, whereas 14 of 18 CMV-seropositive patients developed CMV antigenemia after SCT. CMV-seropositive recipients of grafts from CMV-seronegative donors required more preemptive treatment with ganciclovir (GCV) than those of grafts from CMV-seropositive donors (3 [1-6] versus 1 [0-3] courses, respectively; P =.009). The number of A2-NLV-specific CD8+ T cells in the grafts correlated inversely with the number of preemptive GCV courses administered (r = -0.61; P =.01). None of the 9 CMV-seronegative patients mounted a CMV-specific immune response as measured by monitoring A2-NLV-specific CD8+ T cells after SCT. Thirteen of 14 CMV-seropositive patients without CMV disease recovered these T cells. In spite of preemptive GCV treatment, CMV disease developed in 4 patients, who all failed to recover A2-NLV-specific CD8+ T cells after SCT (P =.002). Thus, enumeration of HLA-restricted, CMV-specific CD8+ T cells in the grafts and monitoring of these T cells after SCT may constitute a rapid and sensitive tool to identify SCT recipients at risk for developing CMV disease.     

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   

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.     

Pancreatic Hyperamylasemia and Hyperlipasemia in Association with Cytomegalovirus Infection Following Unrelated Cord Blood Transplantation for Acute Myelogenous Leukemia

Cytomegalovirus (CMV)-associated pancreatitis is rare after allogeneic hematopoietic stem cell transplantation (SCT). We describe a patient who developed pancreatic hyperamylasemia and hyperlipasemia in association with CMV infection after cord blood transplantation (CBT). A 31-year-old man with acute myelogenous leukemia underwent CBT. A neutrophil count consistently greater than 500/microL was achieved on day +21. Positive results for CMV antigenemia on days +35 and +67 prompted 2 courses of preemptive therapy with ganciclovir or foscarnet. The CMV antigenemia value again became positive on day +134. On day +141, serum amylase and lipase activities markedly increased to 1221 IU/L and 894 IU/L, respectively. The patient had no abdominal symptoms. Ultrasonography and computed tomography results showed no abnormalities of the pancreas. A diagnosis of possible pancreatitis was made. After the initiation of foscarnet therapy, the CMV antigenemia results soon became negative, and serum amylase and lipase activities returned to normal. Therefore, CMV infection was considered to play a major role in the development of pancreatic hyperamylasemia and hyperlipasemia in our patient. The present report indicates that CMV infection should be included in the differential diagnosis for patients with pancreatic hyperamylasemia after SCT.     

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.     

High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection.

The impact of cytomegalovirus (CMV) serostatus (seropositive [(+)] or seronegative [(-)]) of the donor (D) and recipient (R) on mortality after allogeneic non-T cell-depleted stem cell transplantation (SCT) in the era of preemptive therapy was assessed among 1750 patients by means of multivariable Cox regression models. In an analysis that included only pre-SCT variables, D(+)/R(+) and D(+)/R(-) patients had the highest risk for mortality. After neutropenia or the occurrence of CMV disease was controlled for, only D(+)/R(-) patients remained at a significantly higher risk for mortality. Mortality due to bacteremia or invasive fungal infection was higher among D(+)/R(-) (18.3%) than D(-)/R(-) (9.7%) patients (P <.001). Thus, CMV serostatus remains associated with mortality; neutropenia due to ganciclovir administration and CMV disease explain the association with mortality among seropositive recipients. However, in D(+)/R(-) subjects, mortality appears to be associated with bacterial and fungal infection, indicating a possible immunomodulatory effect of primary CMV infection that was undetected despite intensive monitoring.     

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.     

Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

A retrospective study was performed to collect information regarding efficacy and toxicity of cidofovir (CDV) in allogeneic stem cell transplant patients. Data were available on 82 patients. The indications for therapy were cytomegalovirus (CMV) disease in 20 patients, primary preemptive therapy in 24 patients, and secondary preemptive therapy in 38 patients. Of the patients, 47 had received previous antiviral therapy with ganciclovir, foscarnet, or both drugs. The dosage of CDV was 1 to 5 mg/kg per week followed by maintenance every other week in some patients. The duration of therapy ranged from 1 to 134 days (median, 22 days). All patients received probenecid and prehydration. Ten of 20 (50%) patients who were treated for CMV disease (9 of 16 with pneumonia) responded to CDV therapy, as did 25 of 38 (66%) patients who had failed or relapsed after previous preemptive therapy and 15 of 24 (62%) patients in whom CDV was used as the primary preemptive therapy. Of the patients, 21 (25.6%) developed renal toxicity that remained after cessation of therapy in 12 patients. Fifteen patients developed other toxicities that were potentially due to CDV or the concomitantly given probenecid. No toxicity was seen in 45 (61.6%) patients. Cidofovir can be considered as second-line therapy in patients with CMV disease failing previous antiviral therapy. However, additional studies are needed before CDV can be recommended for preemptive therapy.     

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.