***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Varicella-zoster virus ( VZV ) disease occurs in 30 % of allogeneic hematopoietic cell transplant recipients who had a history of VZV infection . A safe and effective prevention strategy has not been established . In a double-blind controlled trial , 77 hematopoietic cell transplant recipients at risk for VZV reactivation were r and omized to acyclovir 800 mg twice daily or placebo given from 1 to 2 months until 1 year after transplantation .  VZV disease at 1 year was the primary end point ; VZV disease after discontinuation of prophylaxis , VZV-specific T-cell immunity , herpes simplex virus ( HSV ) infection , cytomegalovirus ( CMV ) disease , survival , and safety were secondary end points . Acyclovir significantly reduced VZV infections at 1 year after transplantation ( HR , 0.16 ; 95 % CI , 0.035 - 0.74 ; P = .006 ) . In the post-intervention observation period , this difference was not statistically significant ( 2 years : HR , 0.52 ; 95 % CI , 0.21 - 1.3 ; 5 years : HR , 0.76 ; 95 % CI , 0.36 - 1.6 ) . There was no statistically significant difference in reconstitution of VZV-specific T-helper cell responses , HSV infections , CMV disease , chronic graft-versus-host disease , and overall survival between the groups . Acyclovir was well tolerated . Post- study VZV disease predominantly occurred in patients with continued need for systemic immunosuppression . In conclusion , acyclovir  effectively and safely prevents VZV disease during the first year after hematopoietic cell transplantation . Periods of prophylaxis longer than 12 months may be beneficial for those hematopoietic cell transplant recipients on continued immune suppression Protection from cytomegalovirus ( CMV ) disease in immunocompromised hosts has been shown to correlate with recovery of the host virus-specific CD8 + T-cell response . The administration of ganciclovir to immunosuppressed transplant recipients as antiviral prophylaxis has reduced the early risk of CMV disease , but late disease is observed with increased frequency , suggesting that recovery of the CMV-specific T-cell responses necessary for protective immunity may be delayed in these patients . Therefore , we evaluated reconstitution of CMV-specific T-cell responses in 47 bone marrow transplant ( BMT ) recipients entered on a r and omized placebo-controlled study of ganciclovir .  The study drug was initiated at a mean of 24 days after BMT . At day 30 to 40 , a minority of patients had recovery of T-cell immunity to CMV and the frequency of reconstitution was equivalent in patients r and omized to ganciclovir or placebo . The failure of ganciclovir to effect early reconstitution may reflect the short duration of treatment . Early recovery was associated with the infusion of BM from a CMV seropositive donor ( P = .07 for CD8 + cytotoxic T cell ( CTL ) , P = .04 for CD4 + Th ) . Between day 40 and day 90 , recovery of deficient CD8 + and CD4 + CMV-specific T-cell responses occurred in the majority of individuals that received placebo , but in a minority of ganciclovir recipients . Two cases of late-onset CMV disease occurred in ganciclovir recipients . In all patients , the presence of a CTL response to CMV conferred protection from subsequent CMV disease ( P = .005 ) , and these protective CTL responses are shown to be specific for structural virion proteins similar to the responses in immunocompetent CMV seropositive individuals . These data confirm the importance of CMV-specific T-cell responses and suggest that a delay in recovery of these responses as a result of ganciclovir prophylaxis may contribute to the occurrence of late CMV disease Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased  patient and allograft survival .  We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation , and that a short- duration ganciclovir (GCV)-based regimen would obviate the need for long-term antiviral agent administration , perhaps serving to interdict CMV infection and disease as well as , or perhaps even more effectively than , a more prolonged , oral acyclovir (ACV)-based form of prophylaxis . A total of 311 patients were stratified according to allograft type , age , and presence or absence or diabetes mellitus , and were then r and omized to receive either long- duration ACV prophylaxis ( 800 mg orally or 400 mg i.v . q.i.d . for 12 weeks after transplantation or 6 weeks after any antirejection therapy ) versus short- duration GCV ( 5 mg/kg/12 hr i.v . for 7 days after transplant or after any antirejection therapy ) plus human immune globulin ( HIg ; S and oglobulin or Minnesota CMV immune globulin ) 100 mg/kg i.v . administered on days 1 , 4 , and 7 after transplant or after any antirejection therapy . A total of 266 patients ( ACV , n = 133 ; GCV+HIg , n = 133 ) completed the protocol and were available for follow-up . CMV disease occurred in fewer patients ( n = 28 , 21.0 % ) in the ACV group , while significantly more patients ( n = 42 , 31.6 % ) in the GCV + HIg group developed group developed CMV disease slightly later ( 2.83 + /- 0.70 months ) than those who received GCV/HIg ( 2.15 + /- 0.21 months , P > 0.01 ) . Multivariate analysis demonstrated ( 2.15 + /- 0.21 months , P > 0.1 ) . Multivariate analysis demonstrated that receiving antirejection therapy , a liver transplant , or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease ( P < 0.001 ) , while the difference between ACV versus GCV + HIg prophylaxis was also significant ( P = 0.054 ) . No differences in actuarial patient or allograft survival , however , were noted between the 2 prophylaxis groups . Overall , ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease , although this effect was diminished in high-risk groups of patients . Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration , and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short- duration GCV + HIg prophylaxis is used in this patient population Cytomegalovirus ( CMV ) disease has been an important source of morbidity and mortality during allogeneic marrow transplant [ 1 , 2 ] . Patients who are CMV seropositive , regardless of the donor status , have an incidence of 69 % infection with CMV [ 2 ] . Despite recent advances in antiviral therapy , established CMV disease is difficult to treat . Cytomegalovirus interstitial pneumonia remains a disease with a mortality rate of between 30 % and 55 % [ 3 - 5 ] . Adequate therapy for CMV gastrointestinal disease in patients with marrow transplant has not been well defined [ 6 ] . Ganciclovir , an acyclic nucleoside analog , has been shown to have activity against CMV in the treatment of CMV infection in immunocompromised hosts [ 7 - 9 ] . In a recent attempt to prevent CMV disease , ganciclovir was given to marrow transplant recipients excreting CMV after transplant but before CMV disease was diagnosed [ 10 , 11 ] . Both early treatment studies showed a significant clinical and statistical reduction in CMV pneumonia , gastrointestinal disease , and death after marrow transplantation but failed to identify patients diagnosed with CMV disease without previous positive surveillance cultures . An alternative approach to early treatment strategies is to give ganciclovir at the time of engraftment to all patients who are CMV seropositive . The advantage of this prophylaxis strategy , compared with early treatment strategies , is the inclusion of all patients at risk for developing CMV disease . The concern with ganciclovir prophylaxis is myelosuppression . Therefore , we have performed a r and omized placebo-controlled trial of ganciclovir given to CMV-seropositive allogeneic marrow transplant recipients at the time of engraftment and before CMV excretion or disease . Methods Patients Patients who were CMV seropositive before transplant and were to receive an allogeneic marrow transplant for hematologic malignancy requiring total body irradiation or busulfan-cyclophosphamide at the Fred Hutchinson Cancer Research Center were eligible for study entry . Signed informed consent was obtained according to Food and Drug Administration and institutional guidelines . Protocol Design Patients were entered into this double-blind study before transplant and were followed with weekly viral cultures . Patients were assigned r and omly to receive ganciclovir or placebo at the time of engraftment , which was defined as an absolute neutrophil count of 0.750 109/L or greater for 2 consecutive days . Ganciclovir was given at a dose of 5 mg/kg body weight , administered intravenously twice daily for 5 days and then once daily until day 100 after transplant . Patients were excluded from the study if they received a T-cell-depleted transplant , were younger than 2 years of age , had a serum creatinine level greater than 220 mol/L , were allergic to acyclovir or ganciclovir , had received a marrow transplant in the previous 6 months , or had documented CMV excretion before r and omization . Patients received high-dose acyclovir prophylaxis from the time of conditioning until engraftment [ 12 ] . Virus cultures were obtained from urine , blood , and throat on a weekly basis through day 100 or until leaving Seattle , whichever was longer . All patients who began to excrete virus were removed from the study and treated with ganciclovir [ 11 ] . Viral infection was defined as recovery of virus from the throat , urine , or blood . Disease caused by CMV was defined as recovery of virus from a visceral site ( lung , gastrointestinal tissue ) or by bronchoalveolar lavage in patients who had associated signs ( pulmonary infiltrate ) and symptoms consistent with CMV infection . Marrow toxicity was defined as an absolute neutrophil count of less than 0.750 109/L for 2 consecutive days . Bacterial or fungal infection was defined as the recovery of the organism from a blood culture or other normally sterile site . Laboratory Procedures Virus cultures included both centrifugation culture [ 13 ] and conventional culture . Conventional cultures were maintained for 5 weeks . Statistical Design Study end points were the development of CMV infection and marrow toxicity . Development of CMV disease and death were secondary end points . The analysis of infection , disease , toxicity , and mortality was evaluated from start of the study drug to day 100 after transplant . Mortality and disease were analyzed at 180 days after transplant . Comparison of time to specific events was done according to the method of Kaplan-Meier [ 14 ] with analysis by log-rank test [ 15 ] . Other comparisons were done using the chi-square test , Fisher exact test , Student t-test , or the Wilcoxon test , as appropriate . Fifty patients were entered into the study at which point a scheduled interim analysis was performed . A difference in the incidence of CMV infection between study arms at P = 0.005 was required to stop the study . At the completion of the interim analysis , a statistically significant difference between the study arms for CMV infection was found at the P = 0.005 level , and the study was terminated . Seventy patients had been enrolled in the study by the time the interim analysis had been completed . Sixty-four patients were included in the final analysis . Results From November 1990 to August 1991 , 114 consecutive CMV-seropositive patients were eligible for the study . Twenty-one patients were not enrolled , with three refusing study entry and three receiving T-cell-depleted marrow transplants . The other 15 patients were enrolled in protocol s that precluded ganciclovir administration or conflicted with the blinded design of our study . Ninety-three patients were entered into the study before transplant . Between transplant and engraftment , 23 patients became ineligible for study before r and omization with acute renal failure ( eight patients ) , hematologic relapse ( eight patients ) , refusal ( three patients ) , failure to engraft ( two patients ) , and positive culture for CMV ( two patients ) . Seventy patients were r and omized at engraftment and received the study drug . When the interim analysis showed a difference between the ganciclovir and placebo arms , the study was stopped . Five of the 70 patients had not reached an end point when the result of the interim analysis became available . All five of these patients had been enrolled in the study less than 2 weeks and are not included in the final analysis but were treated with ganciclovir during the remainder of their transplant course . None of these five patients developed CMV excretion or disease during the first 100 days after transplant . One additional patient was excreting CMV the day before study entry and received two doses of study drug before culture results became available . This patient was withdrawn from 
    Output:
    
CONCLUSIONS Antiviral prophylaxis reduced mortality with a small NNT in the post-engraftment setting of allogeneic HSCT .
In the pre-engraftment phase and during chemotherapy only viral-related morbidity was reduced