Cytomegalovirus Antibody Status Research Articles

One Year of Preemptive Valganciclovir Administration in Children After Liver Transplantation

ObjectivesValganciclovir (VGCV) is used as prophylaxis against cytomegalovirus (CMV) infection after pediatric living donor liver transplantation (LDLT). The purpose of this study was to examine the efficacy of 1 year of preemptive VGCV administration compared with a shorter administration after pediatric LDLT. MethodsVGCV was administered to 56 children who underwent LDLT. CMV and Epstein-Barr virus (EBV) antibody status, pp65 antigenemia, and other laboratory data were assessed at 1 year after LDLT. Patients were divided into the 1-year group (n = 32) (patients who had 1 year of VGCV administration) and the <1-year group (n = 24) (patients who had less than 1 year of VGCV administration). ResultsStudy participants consisted of 34 females and 22 males, with a mean age of 4.2 years at transplant. Regarding pretransplant donor (D)/recipient (R) CMV antibody status, 13 were D positive (+)/R negative (-), 27 were D+/R+, 8 were D-/R+, and 8 were D-/R-. For EBV, 22 were D+/R+, 32 were D+/R-, and 2 were D-/R-. In the 1-year group, only 2 patients (6.5%) developed CMV infection, whereas 8 patients (33.3%) developed CMV infection in the <1-year group. The CMV pp65 antigenemia assay was positive in 2 patients. CMV IgM was positive in 7 patients. One year of preemptive VGCV administration was associated with a lower incidence of CMV infection (P = .008), but not EBV infection. No adverse effects were observed. ConclusionsOne year of preemptive VGCV administration after LDLT is safe and suppresses CMV infection. It was useful after pediatric LDLT.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids. We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses. During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group. High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Cytomegalovirus antibody status at 17–18 weeks of gestation and pre‐eclampsia: a case–control study of pregnant women in Norway

To assess the association between maternal cytomegalovirus (CMV) antibodies in mid-pregnancy and pre-eclampsia. Nested case-control study. Pregnancies registered in the Norwegian Mother and Child Cohort Study (MoBa): a large population-based pregnancy cohort (1999-2006). A cohort of 1500 women with pre-eclampsia and 1000 healthy pregnant women. Plasma samples and pregnancy-related information were provided by the MoBa. Antibody status (CMV IgG and CMV IgM) and levels (CMV IgG) at 17-18 weeks of gestation were determined by enzyme-linked immunosorbent assay (ELISA). A diagnosis of pre-eclampsia, as defined in the Medical Birth Registry of Norway. There was no evidence of an effect of CMV IgG seropositivity on the likelihood of developing pre-eclampsia, and CMV IgG antibody levels among women who were seropositive did not differ between groups. Adjusted for maternal age, parity and smoking, the odds ratio for pre-eclampsia in women seropositive for CMV IgG was 0.89 (95% CI 0.74-1.05; P = 0.17). The proportions of women who were seropositive for IgM did not differ between women with pre-eclampsia and women who were healthy (P = 0.98). Among nulliparous women, the proportion of women who were seropositive for CMV IgG was slightly lower among women with pre-eclampsia (53.5%) than among healthy women (59.8%) (P = 0.03). Subgroup analyses were performed for women with early or late onset pre-eclampsia, with preterm delivery and/or with neonates that were small for gestational age, but antibody status did not differ between pre-eclampsia subtypes and controls. The presence of maternal antibodies to CMV was not associated with pre-eclampsia in our study. The results suggest that CMV infection is unlikely to be a major cause of pre-eclampsia.

Maternal antibodies against cytomegalovirus in pregnancy and the risk of fetal death and low birth weight

The aim of this study was to assess the impact of maternal cytomegalovirus (CMV) antibody status in pregnancy on the risk of fetal death and of low birth weight. The study of fetal death risk was a nested case-control study. Cases were all women within a cohort of 35,940 pregnant women in Norway 1992--94, who experienced fetal death after 16th week of gestation (n=281). Controls were 957 randomly selected women with live born children. Both groups were identified through linkage to the Norwegian Medical Birth Registry. The risk of low birth weight was studied in the live born children. Seventy-two percent (203/281) of the cases and 69% (662/957) of the controls had CMV immunoglobulin G (IgG) antibodies in the first trimester (P=0.3). 0.4% (1/281) of the cases and 0.7% (7/957) had CMV IgM antibodies in the first trimester (P=0.7). Among 322 initially CMV antibody-negative women, 11% (6/55) of the cases and 9% (24/267) of the controls had occurrence of CMV IgG and/or IgM antibodies (P=0.7) during pregnancy. Also, after control for maternal age, parity, and follow-up time, no association between CMV antibodies and fetal death was found. CMV antibody status was not associated with low birth weight. This study does not support a causal relation between CMV infection in pregnancy and fetal death or low birth weight.

A comparative randomised study of valacyclovir vs. oral ganciclovir for cytomegalovirus prophylaxis in renal transplant recipients

An open, prospective, randomised study was conducted to compare the safety and efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. Eighty-three renal transplant recipients were assigned randomly to receive valacyclovir (n=43) or oral ganciclovir (n=40) for the first 3 months after transplantation. Both groups were similar in terms of demographics, primary renal disease, graft source, HLA matching, immunosuppressive therapy and donor-recipient CMV antibody status. CMV infection was diagnosed by detection of virus DNA in plasma with the Amplicor CMV Test. CMV disease was observed in only one patient belonging to the ganciclovir group, who developed enterocolitis 6 months post-transplantation. No difference was observed between the two treatment groups with respect to detection of CMV DNA, virus infections other than CMV, acute rejection episodes, and serum creatinine levels at 3 and 6 months following transplantation. An increased number of bacterial infections was noted in the ganciclovir group (p 0.003). No adverse reactions with either treatment were reported. The estimated cost of valacyclovir treatment was 20% higher than that of ganciclovir treatment. Overall, both valacyclovir and oral ganciclovir were found to be effective and safe for CMV prophylaxis in renal transplant recipients. Decisions regarding prophylactic regimens should include additional criteria, such as cost or possible development of resistance.

Decreased Incidence of Cytomegalovirus Infection in Thymoglobulin-Treated Transplant Patients with 6 Months of Valganciclovir Prophylaxis

To the Editor: Cytomegalovirus (CMV) infection is still the most common opportunistic infection following solid organ transplantation despite the introduction of newer anti-viral medications for prophylaxis, such as ganciclovir, valacyclovir, and valganciclovir (1). We recently reported that the overall incidence of CMV disease at 1 year post transplant was 14% (4% tissue-invasive, 10% non-invasive) in 129 kidney or pancreas transplant recipients with 3 months of ganciclovir or valganciclovir prophylaxis (2). However, of the 18 patients who developed CMV disease, 83% (n = 15) had received thymoglobulin induction treatment, and 25% of all thymoglobulin-treated patients developed CMV disease. Four of 15 (27%) patients had tissue-invasive CMV disease (two CMV colitis, one CMV gastritis, and one CMV nephritis). In light of these findings, we extended CMV prophylaxis with valganciclovir to 6 months in thymoglobulin-treated patients and prospectively investigated the incidence, time-course, and clinical patterns of CMV disease. Thirty-seven consecutive thymoglobulin-treated patients, transplanted between February and December 2002, received 6 months of CMV prophylaxis with valganciclovir 450 mg p.o. q.d. There were 20 males and 17 females; 29 of them were Caucasian or Hispanic, and 8 African-American; ages were 29–67 years. Thirty-two patients received kidney-, and five pancreas transplantation. Median follow-up is 13 months (range 8–19 months). In terms of CMV antibody status, 21 were Donor (D)+/Recipient (R)+, eight were D–/R+, four were D+/R–, and four were D–/R–. All patients received quadruple immunosuppression with thymoglobulin 1.5 mg/kg for 5 days after transplantation, corticosteroids, mycophenolate mofetil (MMF), and microemulsion cyclosporin or tacrolimus. All patients received valganciclovir prophylaxis regardless of donor/recipient CMV antibody status. No patient developed tissue-invasive CMV disease. Only three patients (8%) developed non-invasive CMV disease, characterized by fever, leukopenia (less than 3000) and CMV viremia, as detected by qualitative blood PCR (with Southern blot confirmation). CMV-PCR titers were 4590, 21 900, and over 100 000 in those three patients by quantitative CMV-PCR (Cobas amplicor CMV monitor). Two were D+/R+ and one D–/R–. Patients developed CMV viremia 5–6 weeks after completion of 6 months of CMV prophylaxis. All three patients responded to valganciclovir treatment, and the control CMV-PCR titers were undetectable. A recent phase III clinical trial in D+/R– solid-organ recipients, using valganciclovir at 900 mg daily, demonstrated similar incidences of CMV disease in valganciclovir- or oral ganciclovir-treated patients (3). We preferred to extend the course of valganciclovir treatment to 6 months instead of increasing the dose to 900 mg daily for 3 reasons: A 450-mg dose of prophylactic valganciclovir prevented CMV viremia in all but one of the patients during prophylaxis. Half of our valganciclovir-treated patients required the MMF and/or valganciclovir doses to be decreased or held due to neutropenia at our previous experience (2). Two of them had prolonged neutropenia requiring granulocyte colony stimulating factor. Using higher doses of valganciclovir might have further increased the incidence of neutropenia. Patients with creatinine clearance of less than 60 mL/min are recommended to take 450 mg daily (3, 4). It is unlikely that a kidney transplant recipient will have a better creatinine clearance early after transplantation. These results indicate that 6 months of valganciclovir prophylaxis significantly decreases CMV incidence (from 25% to 8%) in thymoglobulin-treated patients, and abrogates the development of tissue-invasive CMV disease. The expected number of patients with CMV disease in 37 thymoglobulin-treated patients with 3 months of valganciclovir prophylaxis would be nine (three tissue-invasive, six non-invasive). Six months of valganciclovir prophylaxis prevented the development of CMV disease in six patients. To extend the prophylaxis to 6 months is cost effective by decreasing the incidence of CMV disease, to avoid not only the cost of CMV treatment but also the indirect effects of CMV disease, such as chronic rejection, thrombotic microangiopathy, and decreased graft survival.

Does cytomegalovirus status influence acute and chronic rejection in heart transplantation during the ganciclovir prophylaxis era?

Background: The effect of cytomegalovirus (CMV) status on acute rejection in heart transplantation is not well understood. Furthermore, there is some evidence to suggest that CMV antibody positivity is associated with cardiac allograft vasculopathy (CAV). Methods: This study compared the effect of CMV antibody status in heart transplant donors (D) and recipients (R) on acute and chronic rejection episodes during the ganciclovir prophylaxis era. Results: All heart transplant recipients at Papworth Hospital during the ganciclovir prophylaxis era were included ( n = 374). They were grouped according to recipients and their respective donor CMV serology: R −/D − ( n = 82); R +/D − ( n = 114); R −/D + ( n = 73); and R +/D + ( n = 105). Ganciclovir prophylaxis was administered to the R −/D + group. The mean (SD) recipient and donor ages were 46 (11), 51 (9), 47 (11) and 52 (8) years ( p < 0.001), and 32 (11), 33 (14), 36 (12) and 38 (14) years ( p = 0.01), respectively, for the CMV groups. The mean number of acute rejection episodes (as confirmed by cardiac biopsy) per 100 patient-days was 0.13 (0.36), 0.11 (0.34), 0.12 (0.34) and 0.12 (0.34), respectively ( p > 0.05) There was no statistical difference in the development of CAV as assessed by angiography ( p = 0.92). At 2 years, the “freedom from CAV” rates were 96%, 97%, 97% and 98%, respectively. The 5-year post-operative survival rates were 83%, 79%, 67% and 73% ( p = 0.08 overall). Conclusions: CMV status of heart transplant recipients and their respective donors does not influence acute or chronic rejection in terms of cardiac allograft vasculopathy.

Cytomegalovirus antibody status of donor/recipient does not influence the incidence of bronchiolitis obliterans syndrome in lung transplantation

Background: We have previously reported that prophylaxis for cytomegalovirus (CMV) infection does not influence the incidence of bronchiolitis obliterans syndrome (BOS) at 2 years. The effect of CMV infection (without evidence of disease) on BOS is still not well understood. Moreover, the incidence and risk factors for development of BOS in CMV-antibody-negative donor/recipient matches in lung transplantation have not been described. The aim of this study is to determine the incidence of BOS in lung transplant patients with CMV-antibody-negative (−) donors (D) and recipients (R), and to evaluate the risk factors that predispose to BOS in this sub-group. Method: A retrospective study of data from the transplant database of our center was performed. All single-lung (SL), double-lung (DL) and heart–lung block (HL) transplant patients who survived >2 years post-transplant were included in the study group. They were grouped as follows: D −/R −, n = 102; D −/R +, n = 70; D +/R −, n = 33, and D +/R +, n = 92. Results: The 3-year BOS-free survival rates were 65%, 56%, 58% and 67%, respectively, and the incidence rates of BOS at 5 years post-transplant in the different groups were 57%, 62%, 78% and 55% ( p > 0.05). In the D −/R − group, the significant risk factor for developing BOS was three or more episodes of acute rejection ( p = 0.02). The mean numbers of acute rejection episodes per 100 patients-days within the first 6 months were 1.28, 1.06, 0.50 and 1.11 ( p < 0.001 overall) for the four groups, respectively. Conclusion: Although CMV is believed to be a risk factor for BOS, its absence did not affect the occurrence or incidence of BOS in lung transplant patients. The main risk factor for BOS in the CMV-antibody-negative population remains the number of acute rejection episodes within the first 6 months after transplantation.

Short-term angiopeptin therapy and the incidence of graft vessel disease after heart transplantation

Background Graft vessel disease, the major limitation for long-term success after heart transplantation, is triggered by injury to the graft vessel endothelium, resulting in the expression of adhesion molecules, the migration of leukocytes into the graft, and the release of growth factors. Angiopeptin, a stable analog of somatostatin, is a growth-hormone inhibitor with additional anti-proliferative effects. We evaluated angiopeptin for prevention of graft vasculopathy after cardiac transplantation in the first prospective, randomized, double-blind, clinical trial. Methods Thirty-one patients received treatment with either angiopeptin ( n = 13) or placebo ( n = 18). Patients were randomized according to the presence of hypercholesterolemia, recipient cytomegalovirus-antibody status, and donor age. All patients received standard triple-drug immunosuppression. Angiopeptin 1.5 mg or placebo was given subcutaneously immediately before surgery and twice a day after transplantation from Day 1 to Day 14. Furthermore, 1.5 mg was added to each liter of cardioplegic solution, 1.5 mg was given intravenously during surgery, and another 3 mg was given during the first 6 post-operative hours. During the first post-operative year, angiopeptin 1.5 mg or placebo was added to each treatment for acute rejection (twice a day subcutaneously). Baseline angiography was performed within the first 4 post-operative weeks and annually thereafter. Twenty-three patients each underwent an additional intracoronary ultrasound. Results One- and 4-year survival rates were comparable: 85% and 85% for the group receiving angiopeptin, and 89% and 78% for the placebo group, respectively. One patient in the control group died of myocardial infarction caused by graft vessel disease. Although the mean number of rejection and infection episodes was similar, the overall incidence of newly occurring graft vessel disease after 2 and 4 years was greater in the control cohort: 9% vs 38% after 2 years and 27% vs 44% after 4 years ( p = 0.183, 0.448). Comparison of the results of intracoronary ultrasound performed in a sub-group of patients confirmed that trend: the modified Stanford score, the mean intimal thickness, and the mean intimal index were lower in the angiopeptin group. Again, because of the relatively small number of patients available for evaluation, the difference did not reach statistical significance. Conclusions Short-term peri-operative angiopeptin treatment along with additional injections during rejection episodes within the first year resulted in a marked decrease in graft vessel disease 2 and 4 years after heart transplantation. Based on our results, continuous, long-term application of slow-release angiopeptin could significantly decrease or even prevent graft vessel disease.

Associations between HLA-DQB1 high risk alleles and type 1 diabetes do not depend on cytomegalovirus antibody status at onset: A case-parent study conducted in Chile.

Associations between HLA-DQB1 high risk alleles and type 1 diabetes do not depend on cytomegalovirus antibody status at onset: A case-parent study conducted in Chile.

Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study

Results from the previous times (Times 1–3) of the Swedish longitudinal OCTO immune study indicated that a combination of high CD8 and low CD4 percentages and poor T-cell proliferation in PBL was associated with a higher 2-year mortality in a sample of very old Swedish individuals. The combination of immune parameters was closely related to an inverted CD4/CD8 ratio. In the present study at Time 4 (T4) results are reported from the final follow-up of this longitudinal study, 8 years after it was initiated in 1989. An additional goal at this time point was to examine the immune system alterations in the very old in relation to evidence of lymphocyte activation and cytomegalovirus antibody status. In the present study immune system changes were identified that suggest a loss of T-cell homeostasis, as reflected by a decrease in the number of CD4 cells and a very significant increase in the number of CD8 cells in individuals with an inverted CD4/CD8 ratio. When considered over the duration of the OCTO study the inversion occurred in a high percentage (32%) of the individuals included in the original sample and was associated with non-survival. At T4 the changes were apparent in a number of the T-cell subsets, but particularly in the CD8 +CD28 − and CD57 + subsets. T-cell activation was significantly associated with the inversion of the CD4/CD8 ratio. In this very old sample the subset alterations were associated with evidence of cytomegalovirus (CMV) infection.

The impact of cytomegalovirus serology for 7-year graft survival in cadaveric kidney transplantation - the Newcastle experience

Abstract To analyse the contribution of cytomegalovirus (CMV) serology to long-term graft survival in cadaveric kidney transplantation, 404 transplants from a single centre were divided into four subgroups with respect to the combination of donor and recipient CMV antibody status. Graft survival was estimated according to Kaplan-Meier for 1, 3, 5 and 7 years post-transplantation. The single-centre results confirm a negative impact of CMV-positive donor organs for initial graft survival in CMV-negative recipients within the first 3 years after transplantation. However, when 5- and 7-year long-term graft survival was studied, Donor +/Recipient - pairs showed a favourable long-term result, whilst D +/R - pairs had surprisingly a poorer outcome. Therefore, the concept of avoiding transplantation in the D +/R + CMV serology group should be ignored whereas attempts could be made to improve the poor long-term outcome of D +/R + pairs or to reduce its size by organ allocation.

The impact of cytomegalovirus serology for 7-year graft survival in cadaveric kidney transplantation--the Newcastle experience.

To analyse the contribution of cytomegalovirus (CMV) serology to long-term graft survival in cadaveric kidney transplantation, 404 transplants from a single centre were divided into four subgroups with respect to the combination of donor and recipient CMV antibody status. Graft survival was estimated according to Kaplan-Meier for 1, 3, 5 and 7 years post-transplantation. The single-centre results confirm a negative impact of CMV-positive donor organs for initial graft survival in CMV-negative recipients within the first 3 years after transplantation. However, when 5- and 7-year long-term graft survival was studied, Donor +/Recipient - pairs showed a favourable long-term result, whilst D +/R - pairs had surprisingly a poorer outcome. Therefore, the concept of avoiding transplantation in the D +/R + CMV serology group should be ignored whereas attempts could be made to improve the poor long-term outcome of D +/R + pairs or to reduce its size by organ allocation.

Cytomegalovirus seroprevalence in French pregnant women: parity and place of birth as major predictive factors.

In this study we present data on cytomegalovirus (CMV) seroprevalence in pregnant women in France. One thousand and eighteen women were enrolled in a prospective study carried out in Grenoble. The overall rate of seropositivity, using a specific IgG ELISA test, was 51.5 % (95 % CI: 48.5-54.5). Among a homogeneous population of 873 women born in France with high or middle socioeconomic status, CMV seropositivity increased with age and parity. The seroprevalence according to age was found to depend on parity. It increased with age in women with no children or with only one; it was higher but no more age-dependent in women with two children or more. In addition, CMV seroprevalence was significantly higher in women born in southern France (51.6%) than in those born in northern France (37.4%), these findings being consistent with the existence, within France, of a gradient in seroprevalence rate, increasing from the North to the South. A logistic regression analysis reveals the place of birth in France as a major predictive factor of CMV antibody status (OR: 3.5) followed by age (OR: 2) and parity (OR: 1.7). In this study, we show an independent effect of parity on CMV seroprevalence, arguing for the importance of child-to-mother transmission; nevertheless, the latitude of the place of birth, even within a size-limited country such as France, appears to be a major predictive factor of CMV seroprevalence.

Cytomegalovirus as a cause of morbidity in heart transplantation. The experience of one center.

The accumulated data from 78 heart transplant recipients surviving for more than one month postoperatively were reviewed; the median duration of follow up was 16 months. Cytomegalovirus (CMV) disease was seen most frequently in recipients of hearts from CMV-seropositive donors, irrespective of the recipient CMV antibody status. CMV-related illness was detected in 13 patients; of the six who developed pneumonitis, five were CMV-seropositive recipients with seropositive donors. CMV was not a common cause of hepatitis or gastrointestinal symptoms.

Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients

SummaryDespite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients.At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p<0·0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0·8%) ganciclovir patients (p=0·002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p=0·001) and negative patients (42 vs 11%, p=0·06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p<0·0001) and disease (p=0·001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups.CMV can be eliminated almost completely as a significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe.

Results of single and bilateral lung transplantation in 131 consecutive recipients

We reviewed results of the first 131 recipients who received a single or bilateral sequential lung transplant at Barnes Hospital between July 1, 1988, and July 31, 1992. Follow-up data were complete as of January 1, 1993, for a minimum of 5 months' follow-up for all surviving recipients. There were 11 hospital deaths for an overall 92 % hospital survival. Thirteen late deaths occurred and 107 (81%) recipients remain alive with a median follow-up period of 19 months. One hundred nineteen recipients survived at least 3 months after transplantation, and for this group factors that might influence long-term results were evaluated. The prevalence of pathologically proved bronchiolitis obliterans was 18.5%. Functional deterioration, which may not correlate with pathologic findings, was evaluated with a recently developed bronchiolitis obliterans syndrome staging system. Factors not influencing longterm outcome included the number of early rejection episodes, matching donor and recipient cytomegalovirus antibody status, or underlying diagnosis. Patients undergoing single lung transplantation for primary pulmonary hypertension or Eisenmenger's syndrome had results similar to those of other diagnostic groups. Furthermore, the hemodynamic improvement previously reported for this group of patients after single lung transplantation has been maintained at long-term follow-up. The shortage of donor organs and the need for improved methods for diagnosis and management of chronic rejection remain the most challenging problems in lung transplantation.

Use of immune globulin to prevent symptomatic cytomegalovirus disease in transplant recipients ‐ A meta‐analysis

The objective of this meta‐analysis was to review the evidence for the use of immune globulin in the prevention of symptomatic cytomegalovirus (CMV) disease in transplant recipients. A computerized search of Medline from 1980 to October 1991 was conducted using the textword “cytomegalo:” and the subheading “prevention and control” for studies in all languages. Reference lists, a manual search of relevant literature and communication with internationally recognized experts were used to locate additional studies. Of the studies identified, 18 met the inclusion criteria (population: transplant recipients; intervention: immune globulin; outcome: symptomatic cytomegalovirus disease; study design: randomized controlled trial). The meta‐analysis of the 18 studies showed a reduction in the incidence of symptomatic CMV disease in the group receiving immune globulin as compared to the untreated group. The common odds ratio was 0.58 (95% C.I. 0.42 to 0.77). Analyses of combining trials by subgroups of polyvalent immune globulin, hyperimmune globulin, bone marrow recipients and solid organ recipients resulted in common odds ratios comparable to the overall common odds ratio. Common odds ratios for the trials reporting cytomegalovirus interstitial pneumonia, cytomegalovirus death, overall death and graft loss ranged from 0.47 to 0.69. Common odds ratios for the effect of immune globulin prophylaxis analyzed by pre‐transplant patient/donor cytomegalovirus antibody status ranged from 0.32 to 0.50. In conclusion, the use of immune globulin as passive immunization for the prevention of symptomatic cytomegalovirus disease in the transplant population is supported by this meta‐analysis. The response is similar in both bone marrow and solid organ transplant recipients. There appears to be no significant clinical advantage in the use of hyperimmune globulin over polyvalent immune globulin.

Risk factors for survival following combined heart-lung transplantation. The first 100 patients.

As the numbers of heart and lung transplant recipients have increased it has become possible to identify major risk factors for early (within 3 months) and later (after 3 months) death after this procedure. For 100 patients receiving organs between April 1984 and February 1991, and followed up until February 1992, patient characteristics, operative details, and early morbidity were assessed for their effects on early and later deaths. Recipient age, sex, and preoperative diagnosis did not have a significant effect on early (within 3 months) or later death. Positive cytomegalovirus antibody status of donor or recipient conferred greater risk of death within 90 days (odds ratio [OR] = 3.24, P = 0.06). Greater than 2 L blood in the first 24 hr after operation (OR = 6.00, P = 0.05), and ventilation for greater than 24 hr (OR = 4.87, P = 0.006) were significant prognostic indicators of early death. After the first 3 months, the main risk factor for death was rejection in the first 3 months (OR = 1.38 per episode, P = 0.008). Early infection in general and CMV infection in particular were associated with a small increase in risk. This study confirms the importance of matching donor and recipient for CMV and shows that difficulties during operation, reflected in postoperative bleeding and ventilation times increased the chance of early death. Later death was associated with early acute rejection. A detrimental effect of infection, including CMV infection, either does not exist, or is too small to be detected in a study of this size.

HLA mismatching and cytomegalovirus infection as risk factors for transplant failure in cyclosporin-treated renal allograft recipients.

In a study of the effects on renal allograft survival of HLA mismatching, mismatching for cytomegalovirus (CMV) antibody status, and post-transplant CMV infection, 148 cyclosporin-treated renal transplant recipients were given kidneys optimally matched for HLA-A, -B, and -DR antigens but not matched for CMV antibody status. Mismatching for HLA-B and -DR antigens was associated with a greater number of rejection episodes and a lower graft survival, but mismatching for CMV antibody status and posttransplant primary or recurrent CMV infection exerted no effect on graft survival. The role of matching of renal transplant recipients and donors for CMV antibody status in preference to HLA matching (proposed as a means of reducing the mortality associated with primary CMV infection) is discussed.