Hyperimmune Globulin Research Articles

Preparation and development of equine hyperimmune globulin F(ab')2 against severe acute respiratory syndrome coronavirus1

Aim: The resurgence of severe acute respiratory syndrome (SARS) is still a threat because the causative agent remaining in animal reservoirs is not fully understood, and sporadic cases continue to be reported. Developing high titers of anti‐SARS hyperimmune globulin to provide an alternative pathway for emergent future prevention and treatment of SARS. Methods: SARS coronavirus (CoV)F69 (AY313906) and Z2‐Y3 (AY394989) were isolated and identified from 2 different Cantonese onset SARS patients. Immunogen was prepared from SARS‐CoV F69 strain. Six health horses were immunized 4 times and serum was collected periodically to measure the profile of specific IgG and neutralizing antibodies using indirect enzyme‐linked immunosorbent assay and a microneutralization test. Sera were collected in large amounts at the peak, where IgG was precipitated using ammonium sulphate and subsequently digested with pepsin. The product was then purified using anion‐exchange chromatography to obtain F(ab′)2 fragments. Results: The specific IgG and neutralizing antibody titers peaked at approximately week 7 after the first immunization, with a maximum value of 1:14210. The sera collected at the peak were then purified. Fragment of approximately 15 g F(ab′)2 was obtained from 1 litre antiserum and the purity was above 90% with the titer of 1:5120, which could neutralize the other strain (SARS‐CoV Z2‐Y3) as well. Conclusion: This research provides a viable strategy for the prevention and treatment of SARS coronavirus infection with equine hyperimmune globulin, with the purpose of combating any resurgence of SARS.

Use of CMV Hyperimmune Globulin During Pregnancy

Congenital cytomegalovirus (CMV) infection can result in intrauterine growth retardation, organ malformation, and significant neurologic defects. Among

Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection

Currently, there is no effective intervention for a primary cytomegalovirus (CMV) infection during pregnancy. We studied pregnant women with a primary CMV infection. The therapy group comprised women whose amniotic fluid contained either CMV or CMV DNA and who were offered intravenous CMV hyperimmune globulin at a dose of 200 U per kilogram of maternal weight. A prevention group, consisting of women with a recent primary infection before 21 weeks' gestation or who declined amniocentesis, was offered monthly hyperimmune globulin (100 U per kilogram intravenously). In the therapy group, 31 women received hyperimmune globulin, only 1 (3 percent) of whom gave birth to an infant with CMV disease (symptomatic at birth and handicapped at two or more years of age), as compared with 7 of 14 women who did not receive hyperimmune globulin (50 percent). Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio, 0.02; 95 percent confidence interval, -infinity to 0.15; P<0.001). In the prevention group, 37 women received hyperimmune globulin, 6 (16 percent) of whom had infants with congenital CMV infection, as compared with 19 of 47 women (40 percent) who did not receive hyperimmune globulin. Thus, hyperimmune globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio, 0.32; 95 percent confidence interval, 0.10 to 0.94; P=0.04). Hyperimmune globulin therapy significantly (P<0.001) increased CMV-specific IgG concentrations and avidity and decreased natural killer cells and HLA-DR+ cells and had no adverse effects. Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate.

Purification of severe acute respiratory syndrome hyperimmune globulins for intravenous injection from convalescent plasma

BACKGROUND: Severe acute respiratory syndrome (SARS) is a new infectious disease caused by the SARS virus. Current first‐line treatments are experimental, and their effectiveness remains open to question. For more effective treatment and prevention of SARS, human SARS hyperimmune globulins for intravenous (IV) injection were purified in this study. STUDY DESIGN AND METHODS: A combination of cold ethanol precipitation and ion‐exchange chromatography was used to process pooled SARS convalescent plasma samples. Virus inactivation and removal approaches were taken to ensure safety. RESULTS: The purified hyperimmune globulins were formulated as a 5 percent solution, with an antibody titer specifically against the SARS virus of 1:83, 1:1600, and 1:200, as determined by enzyme‐linked immunosorbent assay, immunofluorescence assay, and neutralizing antibody test, respectively. The purity of the SARS hyperimmune globulins was 99.0 percent, and the monomer and dimer content was 100 percent. Other variables analyzed met the Chinese Requirements of Biologics for IV immune globulin. The SARS hyperimmune globulins prepared were subsequently approved for clinical evaluation by the Chinese National Institute for the Control of Pharmaceutical & Biological Products. CONCLUSION: IV‐injectable, purified, and concentrated human SARS hyperimmune globulins were prepared from pooled convalescent plasma samples, which are ready to be further evaluated.

Varicella zoster virus antibody titers after intravenous zoster immune globulin in neonates, and the safety of this preparation

1) To assess the safety of intravenous varicella zoster virus hyperimmune globulin G (IV-VZVIG) in neonates; 2) measure varicella zoster virus-specific IgG antibody (VZVIG) changes in newborn IV-VZVIG recipients. Eighteen neonatal intensive care unit (NICU) neonates with varicella exposure were given 1 ml/kg (43 International Units (IU)/kg) Varitect IV-VZVIG. Serum VZVIG titers were assayed in neonatal recipients 0, 1, 7, 14, 21, 28, and 35 d after IV-VZVIG. Also, serum samples for VZV-IgM antibody determinations were obtained at 4 wk post-infusion. No varicella developed in the 18 infants. Infusion of 1 ml/kg (43 IU/kg) IV-VZVIG was generally safe. The IV-VZVIG dose resulted in seroconversion of a non-immune newborn. Five infants had low basal VZVIG titers, and two of them had a 0.6-log10 increase at 24 h post-infusion. Neonatal VZVIG titers (mean+/-SEM in log(10)) before IV-VZVIG and after by 1, 7, 14, 21, 28, and 35 d were 2.22+/-0.15, 2.17+/-0.17, 2.02+/-0.12, 0.87+/-0.2, 1.09+/-0.19, 2.33+/-0.07, and 2.16+/-0.1, respectively. One ml/kg (43 IU/kg) IV-VZVIG was generally safe. Our neonatal mean VZV-immune status did not significantly increase after the 1 ml/kg (43 IU/kg) IV-VZVIG dose, although no varicella developed and it caused a VZV-specific seroconversion.

The challenge of progressive hepatitis C following liver transplantation

The challenge of progressive hepatitis C following liver transplantation

The CARI guidelines. CMV disease and kidney transplant: prophylaxis for cytomegalovirus infection in patients following renal transplantation.

The CARI guidelines. CMV disease and kidney transplant: prophylaxis for cytomegalovirus infection in patients following renal transplantation.

Plasmapheresis, CMV Hyperimmune Globulin, and Anti-CD20 Allow ABO-Incompatible Renal Transplantation Without Splenectomy

The majority of preconditioning protocols developed to allow ABO-incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful engraftment. Our center has developed a preconditioning protocol that includes plasmapheresis (PP), low-dose CMV hyperimmune globulin (CMVIg), and anti-CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy. Our initial experience has included treatment of six recipients and successful transplantation from blood group A1, A2, and group B living donors. Mean (± SD) serum creatinine was 1.3 ± 0.1 mg/dL among the six recipients and no episodes of antibody-mediated rejection (AMR) occurred at a median follow-up of 12 months. ABO antibody titers have remained below pretreatment levels. The absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation. The use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post-splenectomy infections.

Burdens of disease in southern Africa

20 Ross DJ, Moudgil A, Bagga A, et al. Lung allograft dysfunction correlates with gamma-interferon gene expression in bronchoalveolar lavage. J Heart Lung Transplant 1999; 18: 627–36. 21 Tsubouchi H, Niitani Y, Hirono S, et al. Levels of the human hepatocyte growth factor in serum of patients with various liver diseases determined by an enzyme-linked immunosorbent assay. Hepatology 1991; 13: 1–5. 22 Maeda J, Ueki N, Hada T, Higashino K. Elevated serum hepatocyte growth factor/scatter factor levels in inflammatory lung disease. Am J Respir Crit Care Med 1995; 152: 1587–91. 23 Valantine HA, Luikart H, Doyle R, et al. Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone. Transplantation 2001; 72: 1647–52. 24 Weill D, Lock BJ, Wewers DL, et al. Combination prophylaxis with ganciclovir and cytomegalovirus (CMV) immune globulin after lung transplantation: effective CMV prevention following daclizumab induction. Am J Transplant 2003; 3: 492–96. 25 Defrances MC, Wolf HK, Michalopoulos GK, Zarnegar R. The presence of hepatocyte growth factor in the developing rat. Development 1992; 116: 387–95. 26 Matsumoto K, Tajima H, Hamanoue M, Kohno S, Kinoshita T, Nakamura T. Identification and characterization of “injurin,” an inducer of expression of the gene for hepatocyte growth factor. Proc Natl Acad Sci USA 1992; 89: 3800–04. 27 Yanagita K, Nagaike M, Ishibashi H, Niho Y, Matsumoto K, Nakamura T. Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs. Biochem Biophys Res Commun 1992; 182: 802–09. 28 Hall SM, Odom N, McGregor CG, Haworth SG. Transient ultrastructural injury and repair of pulmonary capillaries in transplanted rat lung: effect of preservation and reperfusion. Am J Respir Cell Mol Biol 1992; 7: 49–57. ARTICLES

Prevention and treatment of HCV recurrence after liver transplantation

Prevention and treatment of HCV recurrence after liver transplantation

Comparison of intravenous ganciclovir and cytomegalovirus hyperimmune globulin pre-emptive treatment in cytomegalovirus-positive heart transplant recipients

Background We compared the use of intravenous ganciclovir and cytomegalovirus hyperimmune globulin (CMVIG) as a pre-emptive treatment for cytomegalovirus (CMV)-positive heart transplant recipients. Methods Of 59 CMV-seropositive adult heart transplant recipients enrolled in Group 1, 37 tested positive for pp65 antigen within 12 weeks post-transplantation. These patients were randomized to receive either intravenous ganciclovir ( n = 23) or CMVIG ( n = 14). Group 2 included 133 CMV-seropositive heart transplant recipients who were not tested for CMV antigenemia and who received no anti-CMV therapy. Results CMV disease developed in 0 of 59 patients from Group 1, and in 27 of 133 patients (20%) in Group 2 ( p = 0.0001). The incidence of superinfections was lower in Group 1 (0.28 ± 0.46) than in Group 2 (1.10 ± 1.33) ( p = 0.01). The 2 groups did not differ with regard to incidence of rejection (0.7 ± 0.9 in Group 1 vs 1.0 ± 1.2 in Group 2; p = NS), transplant coronary artery disease at 1 year (14% in Group 1 vs 16% in Group 2; p = NS) or post-transplant lymphoproliferative disease (0% in Group 1 vs 2% in Group 2; p = NS). Ganciclovir and CMVIG therapies were associated with similar rates of rejection (0.52 ± 0.6 with ganciclovir vs 0.50 ± 0.60 with CMVIG; p = NS), superinfection (0.30 ± 0.48 with ganciclovir vs 0.25 ± 0.46 with CMVIG; p = NS), and transplant coronary artery disease at 1 year (13% with ganciclovir vs 14% with CMVIG, p = NS). Conclusions The pre-emptive anti-CMV approach is superior to prophylaxis in CMV-seropositive heart transplant recipients. Both ganciclovir and CMVIG are equally effective.

Successful Renal Transplantation across Simultaneous ABO Incompatible and Positive Crossmatch Barriers

ABO incompatibility and human leukocyte antigen (HLA) sensitization remain the two largest barriers to optimal utilization of kidneys from live donors. Here we describe the first successful transplantation of patients who were both ABO incompatible and crossmatch positive with their only available donor. A preconditioning regimen of plasmapheresis (PP) and low-dose CMV hyperimmune globulin (CMVIg) was delivered every other day until donor-specific antibody (DSA) titers were reduced to a safe level and isoagglutinin titers were ≤16. Each patient received quadruple sequential immunosuppression, splenectomy and three protocol post-transplant PP/CMVIg treatments. There was no hyperacute rejection. Two of the three patients had a persistent positive cytotoxic crossmatch on the day of transplant and eliminated their DSA subsequently. Antibody-mediated rejection (AMR) in one patient was reversed by reinitiating PP/CMVIg and anti-CD20. The patients are more than 9 months post-transplant with excellent graft function. Preconditioning with PP/CMVIg results in a durable suppression of DSA and permits accommodation of the allograft to a discordant blood type. The ability to cross these two barriers simultaneously is clinically important as sensitized patients have often exhausted their blood type compatible living donors during previous transplants.

Delay of CMV infection in high-risk CMV mismatch lung transplant recipients due to prophylaxis with oral ganciclovir.

Cytomegalovirus (CMV) is a common opportunistic infection in lung transplant recipients. Despite the use of early post-operative intravenous ganciclovir, most high-risk patients develop CMV infection. We conducted this retrospective study to determine the efficacy of extended CMV prophylaxis with oral ganciclovir in high-risk, donor-positive-recipient-negative, lung recipients. All patients initially received 3 months of intravenous ganciclovir and CMV hyperimmune globulin. Clinical outcomes in all CMV mismatch patients undergoing lung transplant surviving at least 3 months were included (n = 42). Since 1998, 14 patients received no oral ganciclovir prophylaxis (group 1) and 28 patients received indefinite oral ganciclovir after completion of intravenous therapy (group 2). In those patients receiving oral ganciclovir, the prevalence of post-transplant CMV infection was significantly reduced over the first 180 d post-transplant (50% in group 1 vs. 4% in group 2; p < 0.001). Although some CMV events were observed with additional follow-up in group 2, there remained a significantly greater freedom from CMV infection by Kaplan-Meier analysis in group 2 as compared with group 1, with over 30 months follow-up time in each group (log-rank, p = 0.02). A moderate rate of drug discontinuation was observed in group 2, and no severe drug-related events occurred. In high-risk lung transplant recipients, CMV prophylaxis with intravenous ganciclovir, followed by indefinite oral ganciclovir, significantly delays and reduces post-transplant CMV infections. A larger prospective randomized study is needed to confirm the benefits of oral ganciclovir on CMV prevention.

O antigen seroepidemiology of Klebsiella clinical isolates and implications for immunoprophylaxis of Klebsiella infections

Prevention of Klebsiella infections by passive immunotherapy has received more attention during the last decade. Both K antigen-and O antigen-specific antisera and monoclonal antibodies (mAbs) have been studied with respect to phagocytosis-enhancing and in vivo protective capacities. Our own work has focussed on the generation of O serogroup-specific rabbit antisera and O antigen specific murine antibodies. O-specific rabbit sera were absorbed extensively with heterologous O antigen strains in order to obtain highly specific typing reagents. Using these for typing a collection of 378 clinical strains, we found that 82% of them belonged to one of the four serogroups O1, O2ab, O3 and O5. Phagocytosis experiments using antisera and mAbs showed that O antigen specific antibodies were able to opsonize non-encapsulated strains, while fully encapsulated bacteria were rather resistant against the opsonizing effect. Nevertheless, in vivo experiments demonstrated a prophylactic effect on both Klebsiella septicemia and pneumonia in a mouse model of lethal infection. Given the limited number of O serogroups, O antigen-specific antibodies may be suited to supplement K antigen-specific hyperimmune globulins for passive immunoprophylaxis of Klebsiella infections.

Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients.

Donor-specific antibody (DSA) is the major barrier to success of kidney transplants. Attempts to deal with this problem have used plasmapheresis to remove antibodies or high-dose pooled immunoglobulin (IVIg) to down-regulate DSA. However, elimination of antibodies by these methods has been limited in duration or scope. We have confirmed the presence of immunoglobulin (Ig)G antibody to one or more donor HLA antigens in 49 patients treated with alternate-day, single-volume plasmapheresis followed by low-dose cytomegalovirus (CMV) hyperimmune globulin (CMV-Ig) combined with quadruple immunosuppression. We examined the effect of the treatment protocol on antibodies to donor HLA, third-party HLA, and nominal antigens. At the end of treatment, 63% of patients had lost antibody to donor HLA, whereas only 27% had lost antibody to third-party HLA (P<0.001). More strikingly, loss of antibody to donor and third-party HLA antigens occurred in 89% and 19%, respectively, of patients followed for 2 or more months after end of treatment (P<0.0001). No elimination of antiviral antibodies tested was seen. With one exception, elimination of DSA appeared to be independent of antibody titer or specificity, the number of different antibody specificities, or whether or not the target antigen was a repeat mismatch. The effect appears to be long lasting, with no return of DSA observed in patients followed for an average of 13 months. Plasmapheresis and low-dose CMV-Ig combined with traditional immunosuppression is effective in producing a specific and durable elimination of antibody to donor HLA.

Variability in standard care for cytomegalovirus prevention and detection in pediatric lung transplantation: survey of eight pediatric lung transplant programs.

Cytomegalovirus (CMV) infection after pediatric lung transplantation is a significant risk factor for morbidity and mortality in the first year after transplantation. Multiple strategies have been reported for CMV prevention among adult lung transplant programs. In contrast, little information has been reported regarding protocols for prevention and detection of CMV from pediatric programs. We conducted a survey to better understand the range of practice patterns for CMV prevention and detection at pediatric lung transplant centers. A self-administered questionnaire was distributed to 11 pediatric lung transplant centers identified through the International Pediatric Lung Transplant Collaborative in September 2002. A member of the lung transplant team from each institution was asked to provide the methods of CMV prevention and surveillance. Eight of 11 centers surveyed responded to the questionnaire accounting for 45.6% (26 of 57) and 100% (three of three) of the pediatric lung transplants performed in the US and UK in 2001, respectively. All centers used prophylactic therapy against CMV with either ganciclovir or valganciclovir with duration ranging from 3.5 wk to indefinitely. Most centers (six of eight) prescribed a prophylactic regimen based on donor and recipient CMV serostatus. Half (four of eight) of the centers report using CMV hyperimmune globulin in addition to an antiviral agent. Method for CMV detection varied widely, including use of conventional viral culture (n = 1), antigenemia (n = 7), and polymerase chain reaction (n = 2). A wide range of strategies is used to prevent and detect CMV in pediatric lung transplant recipients with little empiric evidence demonstrating the optimal approach. A retrospective analysis among these centers is being conducted to evaluate the efficacy of these approaches.

Efficacy of combined lamivudine and adefovir dipivoxil treatment for severe HBV graft reinfection after living donor liver transplantation

Resistance to lamivudine and hyperimmune globulin (HBIG) may cause severe graft reinfection with progression to fulminant hepatic failure in liver transplant recipients. In this report, we describe the clinical course of a patient with perinatally acquired chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma who developed severe fibrosing cholestatic hepatitis after living donor liver transplantation because of the emergence of lamivudine and HBIG-resistant chronic hepatitis B. Immunohistochemistry demonstrated that more than 30% of hepatocytes stained positively for hepatitis B core antigen. Hepatitis B virus sequence analysis revealed several mutations in the polymerase gene (L528M, M552I, M552V) as well as in the surface gene region encoding the immunogenic major hydrophilic loop of the small surface protein (G130N, M133T, D144G). The amino acid exchange at codon 144 has already been described to escape neutralization by HBIG. Combined treatment with lamivudine and adefovir dipivoxil (ADV) was associated with a dramatic biochemical, virological and clinical response with resolution of jaundice, ascites, peripheral edema and pleural effusions. Serum bilirubin normalized, HBV DNA levels significantly decreased and liver biopsy was remarkable for the absence of viral protein. These results indicate that ADV may provide a sustained rescue treatment for aggressive courses of HBV graft reinfection in liver transplant recipients.

Palivizumab for children with congenital heart disease—good news for efficacy, good news for safety

The report by Feltes et al on the efficacy and safety of palivizumab prophylaxis on morbidity of respiratory syncytial virus (RSV) infections in children with hemodynamically significant congenital heart disease is as good as it gets. The current study of palivizumab is razor sharp—planned to avoid potential pitfalls of design, or to better understand unexpected events as found during the efficacy trial of hyperimmune RSV globulin (RSV-IGIV) a decade ago. Randomized, double-blinded, placebo-controlled, multicentered, multinationed, multistratified, adequately powered, objectively judged for multiple outcomes of efficacy and safety and with greater than 95% completing the 6-month protocol—this is a model for clinical research. Findings have been translated rapidly into recommendations for use in this patient population. Ironically, this was the original target population most likely to benefit from RSV prevention, but which was excluded from initial application of palivizumab use because of prior experience of adverse events that occurred during the RSV-IVIG trial. Approximately 50% relative reduction in RSV hospitalization and in total RSV hospital days per 100 children was documented after administration of palivizumab in the current study, with no related adverse events.

Study 1: characterization of acute rejection episodes after pre-emptive plasmapheresis and cytomegalovirus hyperimmune globulin to abrogate a positive crossmatch and allow live donor renal transplantation

P atients who undergo desensitization protocols to allow renal transplantation despite a positive crossmatch to their living donor remain at risk for acute rejection, specifically, antibody-mediated rejection. Our center uses plasmapheresis and cytomegalovirus hyperimmune globulin (PP-CMVIg) to precondition such patients. In this study, we seek to identify those patients at highest risk for antibodymediated rejection, allowing future modifications to decrease the incidence of acute rejection. All 33 patients treated with PP-CMVIg before live donor renal transplant (Feb 1998–Oct 2002) were analyzed. Episodes of acute rejection were confirmed by biopsy. Diagnostic criteria for antibody-mediated rejection included compatible histologic findings, positive C4d immunohistochemical results, and rising donor-specific antibody titer. Acute rejection occurred in 21 of 33 patients (64%), at a median of 9 days after transplantation, and 12 of 21 were diagnosed with antibody-mediated rejection. Antibody-mediated rejection was treated with steroids and additional PP-CMVIg treatments (mean, 4.3); steroids with or without antilymphocyte therapy were used to treat the 9 other cases of acute cellular rejection. Three patients sustained graft loss, as follows: 1 noncompliance, 1 hemolytic uremic syndrome, and 1 associated with patient death from surgical complications. Patients with an initially positive cytotoxic crossmatch (vs flow, P .007), a positive cytotoxic crossmatch at transplant (vs negative, P .032), and patients who required 6 pretransplant PP-CMVIg treatments (P 0.012) had a higher risk of acute rejection. Occurrence of acute rejection was associated with a longer length of stay (16 vs 5 days, P .0001) and lower 1-week creatinine clearance (43 vs 65 mL/min, P .01). Patients who had an episode of acute rejection had no significant change in their current creatinine clearance (75 vs 73 mL/min at 16 months’ mean follow-up, P .9). Patients with antibody-mediated rejection did not have significantly different outcomes compared with those with cellular rejection alone. Intensity of C4d and donor-specific antibody titer did not predict graft function. Donor-specific antibody remains undetectable in 28 of 30 patients with a functioning allograft. Conclusions: Patients receiving PP-CMVIg to abrogate a positive crossmatch are at risk for acute rejection, especially antibody-mediated rejection, but are responsive to additional PP-CMVIg. Acute rejection does not have an impact on graft function at 1 year. Patients with high levels of donor-specific antibody, as evidenced by an initially positive cytotoxic crossmatch, a positive cytotoxic crossmatch at the time of transplantation, and a requirement of more pretransplant PP-CMVIg treatments, are at highest risk for antibody-mediated rejection and require vigilant observation during the first 2 weeks after transplantation. From the Departments of Surgery, Medicine, and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.002

Impact of prophylaxis with cytogam alone on the incidence of CMV viremia in CMV-seropositive lung transplant recipients

Background: Cytomegalovirus (CMV) infection remains a serious problem after lung transplantation. The purpose of this study was to evaluate the efficacy of CytoGam, a CMV hyperimmune globulin (CMV-IGIV), as CMV prophylaxis after lung transplantation. Methods: This prospective, randomized, open-label study compared prophylaxis with CMV-IGIV and no prophylaxis in 44 CMV-seropositive lung transplant recipients. The primary end-point was development of CMV viremia during the first year after transplantation. Results: Cytomegalovirus viremia was detected in 13 of 22 recipients without prophylaxis and in 16 of 22 recipients with CMV-IGIV prophylaxis ( p = 0.19). Cytomegalovirus pneumonitis developed in 8 controls vs in 11 CMV-IGIV recipients ( p = 0.54). We found no significant difference between the groups in the incidence of positive shell vial assays (6.8% ± 6.5% without vs 11.2% ± 10.1% with prophylaxis, p = 0.09) or in the attack rate of CMV pneumonitis (0.41 ± 0.59 episodes/patient without vs 0.86 ± 0.99 episodes/patient with prophylaxis, p = 0.07). Similarly, no difference was apparent in the time to onset of CMV viremia, to detection of CMV DNA in peripheral blood leukocytes by polymerase chain reaction, or to development of CMV pneumonitis. The incidence of acute rejection and bronchiolitis obliterans syndrome and the survival rate during the first post-transplant year did not differ between the groups. Conclusions: Prophylaxis with CMV-IGIV alone did not decrease CMV viremia or pneumonitis, did not decrease the incidence of acute rejection or bronchiolitis obliterans syndrome, and did not affect 1-year survival of CMV-seropositive lung transplant recipients at our center.