Cytomegalovirus Hyperimmune Globulin Research Articles

The critical role of plasmapheresis in ABO‐incompatible renal transplantation

Thousands of patients with chronic renal failure die yearly and are unable to have a kidney transplant due to the severe shortage of donors. Therapeutic plasma exchange (TPE) is performed to remove ABO antibodies and permit ABO-incompatible (ABO-I) kidney transplants, but there is only limited research within this area and a lack of standardized protocols for TPE. This article reviews the literature to provide a historical perspective of TPE for ABO-I kidney transplantation and also provides the Johns Hopkins Hospital protocol with a focus on both titers and TPE. The TPE treatment plan is based on ABO titers with the goal of a titer of 16 or less at the anti-human globulin (AHG) phase before surgery. Pretransplant therapy consists of every-other-day TPE followed immediately by cytomegalovirus hyperimmune globulin. ABO antibody titers are closely monitored before and after transplantation. After transplantation, TPE therapy is performed for all patients to prevent rebound of anti-A and anti-B titers until tolerance or accommodation occurs. TPE is discontinued and reinstituted based on the clinical criteria of creatinine levels, biopsy results, and ABO titer. Fifty-three ABO-I kidney transplants have been completed with no episodes of hyperacute antibody-mediated rejection (AMR) and only three episodes of AMR. One-year death-censored graft survival is 100 percent and patient survival is 97.6 percent. While randomized clinical trials are needed to evaluate the optimal method and protocol to remove ABO antibodies, the current literature and our results indicate a critical role for TPE in ABO-I renal transplantation.

Immunizations and infectious diseases in pediatric liver transplantation

Liver transplantation (LTx) is an established and effective treatment for children with end-stage and metabolic liver disease. Improved surgical techniques and immunosuppressive regimens have led to enhanced short-term and long-term survival rates, which now approach or exceed 90%. Consequently, more children are being referred for LTx, and an increasing numbers of pediatric centers routinely perform this procedure. Infectious complications are an important cause of morbidity and mortality in children undergoing LTx. However, improvements in immune suppression management along with the availability of new antimicrobial agents and diagnostic tools have resulted in improved treatment and preventative regimens, thus reducing the impact of infectious complications on these children. This review provides an overview of the infectious complications and prevention strategies for children undergoing LTx.

High Incidence of Cytomegalovirus Disease in D +/R − Heart Transplant Recipients Shortly After Completion of 3 Months of Valganciclovir Prophylaxis

Cytomegalovirus (CMV) infection remains a serious problem after heart transplantation. Recipients with D(+)/R(-) CMV serostatus often receive prophylaxis with valganciclovir, but the optimal duration of such therapy after heart transplant is unknown. We retrospectively reviewed the clinical course of all adult cardiac transplant recipients with D(+)/R(-) CMV serostatus at the UT Southwestern Medical Center between January 2003 and December 2006. Standard immunosuppression included basiliximab induction therapy and the CMV prophylaxis included CMV hyperimmune globulin, 2 weeks of intravenous ganciclovir and 3 months of oral valganciclovir. Seven patients met the study criteria. Six of the 7 patients (86%) developed CMV disease. Five of these 6 patients presented with CMV disease within 3 months of the cessation of valganciclovir prophylaxis. There was a high incidence of CMV disease in D(+)/R(-) heart transplant recipients despite CMV hyperimmune globulin, 2 weeks of intravenous ganciclovir and 3 months of valganciclovir prophylaxis. CMV infection occurred consistently within 2 to 3 months of cessation of valganciclovir. Alternative strategies for CMV prophylaxis, including an extension of valganciclovir prophylaxis to 6 months after heart transplantation, needs to be investigated.

Resolution of Hydrops Secondary to Cytomegalovirus After Maternal and Fetal Treatment With Human Cytomegalovirus Hyperimmune Globulin

Congenital cytomegalovirus (CMV) is a common infection with limited treatment options. Vertical transmission can lead to fetal death or long-term neurologic injury. We present a case wherein fetal hydrops resolved after maternal and fetal intravenous administration of CMV hyperimmune globulin. A 20-year-old gravida 3, para 0 was referred for Level II ultrasonography secondary to hydrops fetalis. Amniocentesis demonstrated in utero CMV infection. Resolution of hydrops occurred after the administration of CMV hyperimmune globulin to the patient and then to her fetus. Resolution of hydrops secondary to congenital CMV was temporally related to the administration of maternal and fetal hyperimmune globulin.

CMV‐hyperimmune globulin for preventing cytomegalovirus infection and disease in solid organ transplant recipients: a meta‐analysis

The goal of this meta-analysis was to investigate the impact of cytomegalovirus hyperimmune globulin (CMVIG) on cytomegalovirus (CMV) infection, CMV disease, and mid-term survival in solid organ transplant recipients. Medline, EMBASE, and the Cochrane databases were searched since their inceptions until 2006. Inclusion criteria comprised: prospective randomized trials, in solid organ transplantation which received CMV prophylaxis including CMVIG on one of the treatment arms. Random effects models were used to calculate pooled risk ratios (RR) and meta-regression was employed to explain study heterogeneity. Stratified analyses were conducted and Funnel plot was used to assess publication bias. Literature searches identified 11 randomized trials (698 patients; median follow-up: 12 months, range: 3-22 months) including six randomized trials (302 patients) after kidney transplantation. The analysis demonstrated a beneficial effect of the prophylactic use of CMVIG on total survival [RR (95% confidence interval; CI): 0.67 (0.47-0.95)] and prevention of CMV-associated death [RR (95% CI): 0.45 (0.24-0.84)] in solid organ transplant recipients but not kidney transplant recipients [RR (95% CI): 0.35 (0.12-1.04)]. CMV disease was significantly reduced in all recipients receiving prophylactic CMVIG [RR (95% CI): 0.697 (0.57-0.85)]. CMVIG had no impact on CMV-infections and clinically relevant rejections. Prophylactic administration of CMVIG after solid organ transplantation is associated with improved total survival, reduced CMV disease, and CMV-associated deaths.

Prevention of CMV disease in pediatric kidney transplant recipients: Evaluation of pp67 NASBA‐based pre‐emptive ganciclovir therapy combined with CMV hyperimmune globulin prophylaxis in high‐risk patients

A new prevention strategy for CMV infection was evaluated in our pediatric kidney transplant unit. This approach comprises a pre-emptive therapy, based upon the monitoring of CMV pp67 mRNA in whole blood by the qualitative NASBA, combined with prophylactic CMV-IG in high risk (R-/D+) children. Thirty-one kidney transplant children were followed for six months with serial measurements of CMV pp67 mRNA in the blood. The R-/D+ patients were given prophylactic CMV-IG for the first 16 wk after transplantation. I.v. ganciclovir was administered upon CMV detection by NASBA and was discontinued after two consecutive negative results. CMV infection, detected by NASBA, developed in 11 (35%) recipients: one (33%) of the R+/D- patients and 10 (72%) of the R-/D+ patients. CMV disease developed in 9.6% of the patients (3/31), exclusively in the R-/D+ group. These three patients presented concurrently with CMV viremia and disease. It is noteworthy that two of the three patients could not receive a complete course of CMV-IG, and one of the latter two subjects had been treated for acute rejection 15 days before CMV infection. Ganciclovir was given for the 11 cases of primary infection, and for three cases of relapsed CMV infection. pp67 NASBA-based pre-emptive ganciclovir therapy, combined with prophylactic CMV-IG in high-risk patients leads to a lower rate of CMV disease, as long as a complete course of CMV-IG has been administered and ganciclovir is given during the period of treatment for acute rejection in high-risk populations.

Acute rejection episodes in pediatric renal transplant recipients with cytomegalovirus infection

CMV infection is the most important opportunistic virus infection after renal transplantation leading to increased patient mortality, graft loss, risk for acute rejection episodes and impaired renal function. The potential impact of prophylactic anti-viral therapy on long-term graft outcome is relevant. The aim of this study was to evaluate the incidence of CMV infection, its risk factors and long-term outcome in children after renal transplantation. 103 children (mean age 10.6 +/- 5.3, range 1.6-22.0 yr) were monitored weekly for pp65 for the first 6-8 wk after renal transplantation, followed by a monthly monitoring for the first year. CMV infection occurred in 23/103 children (21.1%) with 10 patients (9.7%) developing CMV disease characterized by positive pp65 in the presence of organ involvement. The CMV R-/D+ and R+/D+ serostatus was significantly associated with an increased risk of CMV infection (p < 0.0001 and p = 0.009). 14/28 R-/D+ patients developed CMV infection despite prophylactic treatment with CMV hyperimmune globulin. The incidence of acute rejection episodes after or during CMV infection was significantly increased (p = 0.003) and the D+ serostatus was significantly associated with acute rejection episodes within the first year after transplantation (p = 0.006). In summary the overall incidence of CMV infection in this single center experience is 21.1%. The D+ serostatus represents a serious risk factor for both CMV infection and acute rejection episodes. In future the potential impact of different modalities of prophylactic anti-viral therapy on the prevention of acute rejection should be considered.

Predictors for persistent cytomegalovirus reactivation after T‐cell‐depleted allogeneic hematopoietic stem cell transplantation

Cytomegalovirus (CMV) reactivation occurs in up to 60% of CMV-seropositive recipients after allogeneic hematopoietic stem cell transplantation (HSCT). The incidence of CMV disease among T-cell-depleted HSCT patients has been reported from 5-15%. The incidence of reactivation refractory to antivirals in this population is not well studied. In this retrospective study we characterized the outcome of CMV reactivation in a cohort of 255 adult and pediatric patients who underwent T-cell-depleted HSCT at Memorial Sloan-Kettering Cancer Center from September 1999 through August 2004. CMV infection was monitored by the pp65 antigenemia assay (CMV Ag). Persistent reactivation was defined as antigenemia positivity >21 days on antiviral therapy. Of 118 CMV-seropositive recipients, 69 (58.4%) had reactivated CMV. Twenty of 69 (29%) developed persistent reactivation at first episode of reactivation, and 7 (10%) in subsequent episode. All patients with persistent reactivation received >/=2 antivirals and CMV hyperimmune globulin; 45% received combination antiviral therapy. The median duration of persistent reactivation was 98 days, range 31-256 days. In multivariate analysis, maximum CMV Ag >25 cells/slide was associated with persistent reactivation (odds ratio 16.2%, 95% confidence interval 4-64, P<0.0001). CMV disease occurred in 6/27 (22%) patients with persistent reactivation. Patients with persistent reactivation had lower CD4(+) and CD8(+) lymphocyte counts compared with those with non-persistent reactivation at day +90 post HSCT (P=0.01 and 0.02, respectively). Persistent reactivation occurred in 39% of T-cell-depleted HSCT despite treatment with currently available antivirals. Maximum CMV Ag >25 cells/slide was associated with persistent CMV reactivation. More effective treatment modalities are needed for this high-risk population to reduce CMV-associated morbidity and mortality.

243: Meta-analysis of CMV-hyperimmune globulin studies for the prevention of CMV infection and disease in solid organ transplant recipients

243: Meta-analysis of CMV-hyperimmune globulin studies for the prevention of CMV infection and disease in solid organ transplant recipients

Meta-analysis of CMV-hyperimmune globulin studies for the prevention of CMV infection and disease in solid organ transplant recipients

Objective: Despite numerous studies comparing CMV-immunoglobulins and antiviral agents the optimal prophylaxis of CMV disease after solid organ transplantation remains debated. We conducted a meta-analysis to study the early and mid-term outcomes of CMV-prophylaxis following solid organ transplantation

Placental Enlargement in Women with Primary Maternal Cytomegalovirus Infection Is Associated with Fetal and Neonatal Disease

Serological testing for primary maternal cytomegalovirus (CMV) infection during pregnancy is not routine, but ultrasound studies are routine. Therefore, we evaluated placental thickening in women with primary CMV infection during pregnancy. The study included 92 women with primary CMV infection during pregnancy and 73 CMV-seropositive pregnant women without primary CMV infection. Neonatal CMV transmission was determined by CMV culture of urine samples. Thirty-two women were treated with CMV hyperimmune globulin to either prevent or treat intrauterine CMV infection. Maximal placental thickness was measured by longitudinal (nonoblique) scanning with the ultrasound beam perpendicular to the chorial dish. Programmed placental ultrasound evaluations were performed from 16 to 36 weeks of gestation. At each measurement between 16 and 36 weeks of gestation, women with primary CMV infection who had a fetus or newborn with CMV disease had placentas that were significantly thicker than those of women with primary CMV infection who did not have a diseased fetus or newborn (P<.0001); the latter group, in turn, had placentas that were significantly thicker than those of seropositive control subjects (P<.0001). For both women with and women without diseased fetuses or newborns, receipt of hyperimmune globulin after primary CMV infection was associated with statistically significant reductions in placental thickness (P<.001). Placental vertical thickness values, which are predictive of primary maternal infection, were observed at each measurement from 16 to 36 weeks of gestation, and cutoff values ranged from 22 mm to 35 mm, with the best sensitivity and specificity at 28 and 32 weeks of gestation. Primary maternal CMV infection and fetal or neonatal disease are associated with sonographically thickened placentas, which respond to administration of hyperimmune globulin. These observations suggest that many of the manifestations of fetal and neonatal disease are caused by placental insufficiency.

Acute Rejection and Cardiac Allograft Vascular Disease Is Reduced by Suppression of Subclinical Cytomegalovirus Infection

Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. We sought to determine whether CMV prophylaxis administered for three months after heart transplant would improve patient outcomes. This prospective cohort study of 66 heart transplant recipients compared aggressive CMV prophylaxis (n = 21, CMV hyperimmune globulin [CMVIG] plus four weeks of intravenous ganciclovir followed by two months of valganciclovir); with standard prophylaxis (n = 45, intravenous ganciclovir for four weeks). Prophylaxis was based on pretransplant donor (D) and recipient (R) CMV serology: R-/D+ received aggressive prophylaxis; R+ received standard prophylaxis. Outcome measures were: CMV infection assessed by DNA-polymerase chain reaction on peripheral blood polymorphonuclear leukocytes, acute rejection, and cardiac allograft vascular disease (CAV) assessed by intravascular ultrasound. All patients completed one year of follow-up. RESULTS.: CMV infection was subclinical in all but four patients (two in each group). Aggressively treated patients had a lower incidence of CMV infection (73 +/- 10% vs. 94 +/- 4%; P = 0.038), and an independent reduced relative risk for acute rejection graded > or =3A (relative risk [95% CI] = 0.55 [0.26-0.96]; P = 0.03), as compared with the standard prophylaxis group. Aggressively prophylaxed patients also showed a slower progression of CAV, in terms of coronary artery lumen loss (lumen volume change=-21 +/- 13% vs. -10+/-14%; P = 0.05); and vessel shrinkage (vessel volume change = -15 +/- 11% vs. -3 +/- 18%; P = 0.03). Prolonged (val)ganciclovir plus CMVIG reduces viral levels, acute rejection, and allograft vascular disease, suggesting a role for chronic subclinical infection in the pathophysiology of the most common diseases affecting heart transplant recipients.

Combined CMV Prophylaxis Improves Outcome and Reduces the Risk for Bronchiolitis Obliterans Syndrome (BOS) after Lung Transplantation

The benefit of cytomegalovirus (CMV) hyperimmune globuline in preventing CMV infection after lung transplantation still remains unclear. The aim of this study was to investigate the effect of combined prophylaxis using ganciclovir (GAN) and CMV hyperimmune globulin (CMV-IG) on CMV infection, CMV disease, survival and its role in preventing Bronchiolitis obliterans syndrome (BOS). A consecutive series of 68 CMV high-risk lung transplant recipients (D+/R-, D+/R+), who had a minimum follow-up of 1 year posttransplant were analyzed. Thirty patients (44.1%) received single GAN prophylaxis for 3 months (control group) and 38 recipients (55.9%) received GAN together with CMV-IG 7 times during the first postoperative month (study group). Median follow-up was 16.5 months in the control and 23.8 months in the study group (P = 0.54). Five CMV-related deaths (16.7%) occurred in the control group (P = 0.014). Fifteen recipients suffered from CMV pneumonitis and three patients had CMV syndrome. In the control group, 13 recipients (43.3%) suffered from clinically manifested CMV disease compared to 5 (13.2%) in the study group (P = 0.007). Additionally, recipient survival was significantly better in the study group (P = 0.01). One year freedom from CMV affection was 52.1% in the control and 71.5% in the study group (P = 0.027). Three-year freedom from BOS was significantly higher in the study group (54.3% vs. 82%, P = 0.024). In CMV high risk patients, additional CMV-IG administration seems to be effective to reduce CMV-related morbidity and to avoid CMV-related mortality. Reduced incidence of BOS may result from improved CMV prevention, although randomized trials are warranted.

Staphylococcal Sepsis in Children

n engl j med 353;26 www.nejm.org december 29, 2005 2820 analyses, however, identified no selection bias, and they also indicated that treatment with CMV hyperimmune globulin was an independent predictor of fetal outcome. Furthermore, all relevant biologic data are consistent with our observations, which included the following findings: the CMV hyperimmune globulin contained high levels of neutralizing antibody; the rates of CMV transmission and disease that we observed were in line with those previously reported by others; preexisting maternal immunity is protective against CMV infection and disease; and in experiments in animals going back 25 years, passive immunization is effective.1 We encourage Dr. Revello and her colleagues to conduct confirmatory trials.

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.

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

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.

Long-term outcome of cytomegalovirus high-risk patients after heart transplantation: comparison between two prophylactic regimes – a single-center experience

BACKGROUND: Implantation of a cytomegalovirus (CMV)-positive graft (D+) into a CMV-negative recipient (R–) is a high-risk constellation after heart transplantation (HTX). CMV infection after HTX is associated with increased morbidity, mortality, raised incidence of acute rejection and possibly the development of transplant vasculopathy. In order to further reduce the incidence of CMV infections, a new, antiviral prohylaxis was established in 1997. METHODS: We retrospectively reviewed all mismatched cardiac transplant recipients (D+/R–) who were treated with oral acyclovir combined with CMV-hyperimmune globulin (group I, n = 8, 1995/1996) and compared them with CMV-mismatched (D+/R–) recipients who had postoperatively intravenous ganciclovir and subsequent oral ganciclovir for 90 days (group II, n = 18, 1997–2001). Demographic data of both groups were comparable. The same immunosuppressive regimen was used for the entire study period. RESULTS: Five patients (62.5%) of group I died after a mean of 6.7 ± 7.6 months, 3 patients (37.5%) remain alive for a mean of 80.7 ± 5.2 months after transplantation. In contrast, two patients of group II died (11.1%), whereas 16 patients (88.9%) remain alive for a mean of 41.6 ± 13.0 months (p = 0.004). CMV seroconversion occurred in 6 patients of group I (75%) 7.8 ± 1.9 weeks after HTX and in 9 patients of group II (50%) 44.5 ± 22.7 weeks after HTX (p = 0.01). There were more positive antigenemia tests in group I compared with group II (13.8% vs. 9%, p = NS). Significantly less rejection episodes grade IB or more (ISHLT classification) were noticed in group II (18 of 195 biopsies, 9.2%) than in group I (16 of 89 biopsies, 18.0%) (p = 0.036). CONCLUSIONS: Mortality was significantly lower in the ganciclovir group. Antiviral prophylaxis is able to reduce the incidence and to delay the onset of CMV infection in the high-risk CMV-mismatched population after HTX.