Effect of oral acyclovir or ganciclovir therapy after preemptive intravenous ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus seropositive renal and liver transplant recipients receiving antilymphocyte antibody therapy

BACKGROUND: Organ transplant recipients who are seropositive for cytomegalovirus (CMV) and who are treated with antilymphocyte antibody (ALA) therapy have a high rate of symptomatic CMV disease. The intravenous administration of ganciclovir therapy once daily during ALA therapy decreased the incidence from 24% to 10% in patients receiving ALA as an induction therapy and from 64% to 22% in those treated for rejection. The present study was undertaken to determine whether a more intensive and sustained antiviral regimen could be more effective. METHODS: From April 1995 to December 1997, all CMV seropositive renal and liver transplant recipients who received ALA therapy were treated with intravenously administered ganciclovir (5 mg/kg/day with dose adjusted for renal dysfunction) for the length of ALA therapy and then with orally administered acyclovir (400 mg three times/day) or ganciclovir (1 gm twice/day) for 3 to 4 months. The incidence of CMV viremia and of CMV disease was determined during the 6 months after completion of ALA therapy. RESULTS: Forty-one patients (35 renal and 6 liver transplant recipients) were studied. CMV disease occurred in 2 patients (4.9%), both of whom were treated for rejection; it occurred in 1 of 21 patients (4.8%) treated with orally administered acyclovir, and in 1 of 20 patients (5%) treated with orally administered ganciclovir. The only patient who developed CMV disease in the ganciclovir group had received only 26 days of oral antiviral therapy. No CMV disease was documented in the group of patients receiving ALA therapy as induction therapy. CMV viremia occurred in three patients in the acyclovir group (14.3%) and in one patient in the ganciclovir group (5%). Among renal transplant recipients only, 1 of 35 patients developed CMV disease (2.9%) and no case of CMV disease was documented in patients treated with orally administered ganciclovir. All six patients receiving two courses of ALA therapy each were free of CMV disease. Toxicity of the regimen was minimal, and antiviral resistance did not develop. CONCLUSIONS: Preemptive antiviral therapy with intravenously administered ganciclovir during ALA therapy and then orally administered ganciclovir for 3 to 4 months provides virtually complete protection against the excessive rate of CMV disease that occurs in CMV seropositive allograft recipients receiving ALA therapy.     

Management of posttransplant lymphoproliferative disease in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) after pediatric liver transplantation has been associated with high mortality rates. METHODS: The present study examined 282 consecutive pediatric liver transplant recipients from October 1989 to June 1996 who received primary tacrolimus immunosuppression. The aim was to determine the incidence of PTLD, management strategies, and patient outcome. RESULTS: The incidence of PTLD was 13% (361282) with a mean age of 5.5+/-0.7 years (range 0.6 to 15) at diagnosis. The average time from transplantation to PTLD was 10.1+/-2.1 months. Initial treatment of PTLD consisted of reduction (3 patients) or discontinuation (33 patients) of tacrolimus and initiation of antiviral therapy (intravenous ganciclovir, 14 patients; intravenous acyclovir, 22 patients; or both, 5 patients). Alpha-interferon was used in four patients (two successfully). One patient also received gamma-interferon, chemotherapy, and radiation for a central nervous system lesion. Chemotherapy was also used in one patient with Burkitt's, whereas one patient with a pulmonary lesion received additional radiation therapy. Three patients received supportive surgery for gastrointestinal involvement, and one patient had a splenectomy for hemolysis. Overall mortality was 22% (8/36) with 5 (14%) PTLD-related deaths (disseminated disease, 4 patients; bowel perforation, 1 patient). Of 31 survivors, 23 had acute rejection at a median time of 24 days after PTLD, with 2 patients developing chronic rejection. One patient required retransplantation. Present immunosuppression consists of tacrolimus monotherapy in 14 patients, tacrolimus/prednisone in 8 patients, and none in 6 patients. CONCLUSION: In summary, PTLD can be successfully treated with reduction of immunosuppression and administration of antiviral agents in most patients. The management of rejection after PTLD requires reassessment of disease status and judicious reintroduction of immunosuppression therapy.     

Prevention and preemptive therapy of postransplant lymphoproliferative disease in pediatric liver recipients

BACKGROUND: We have previously reported a 10% incidence of posttransplant lymphoproliferative disease (PTLD) in pediatric patients receiving first liver grafts and primarily immunosuppressed with tacrolimus. To decrease the incidence of PTLD, we developed a protocol utilizing preemptive intravenous ganciclovir in high-risk recipients (i.e., donor (D)+, recipient (R)-), combined with serial monitoring of peripheral blood for Epstein Barr virus (EBV) by polymerase chain reaction (PCR). METHODS: Consecutive pediatric recipients of a first liver graft were immunosuppressed with oral tacrolimus (both induction and maintenance), and low-dose prednisone. EBV serologies were obtained at the time of orthotopic liver transplant in recipients and donors. Recipients were divided into groups: group 1, high-risk (D+R-), and group 2, low-risk (D+R+; D-R-; D-R+). In group 1 (high-risk), all patients received a minimum of 100 days of intravenous ganciclovir (6-10 mg/kg/day), while, in group 2 (low-risk), patients received intravenous ganciclovir during their initial hospitalization and then were converted to oral acyclovir (40 mg/kg/day) at discharge. Semiquantitative EBV-PCR determinations were made at 1-2-month intervals. In both groups, patients with an increasing viral copy number by EBV-PCR had tacrolimus levels decreased to 2-5 ng/ml. Tacrolimus was stopped, and intravenous ganciclovir reinstituted for PTLD. A positive EBV-PCR with symptoms, but negative histology, was defined as EBV disease; PTLD was defined as histologic evidence of polyclonal or monoclonal B cell proliferation. RESULTS: Forty children who had survived greater than 2 months were enrolled. There were 18 children in group 1 (high-risk; mean age of 14+/-15 months and mean follow-up time of 243+/-149 days) and 22 children in group 2 (low-risk; mean age of 64+/-65 months and follow-up time of 275+/-130 days). In group 1 (high-risk), there was no PTLD and one case of EBV disease (mononucleosis-like syndrome), which resolved. In group 2 (low-risk), there were two cases of PTLD; both resolved when tacrolimus was stopped. Both children were 8 months old at time of transplant. Neither received OKT3, and they had one and two episodes of steroid-sensitive rejection, respectively. One child had EBV disease (mild hepatitis), which resolved. CONCLUSIONS: Since instituting this protocol, the overall incidence of PTLD has fallen from 10% to 5% for children receiving primary tacrolimus therapy after OLT. No high-risk pediatric liver recipient treated preemptively with intravenous ganciclovir developed PTLD. Both children with PTLD were less than 1 year at OLT and considered low-risk. However, their positive EBV antibody titers may have been maternal in origin and not have offered long-term protection. Serial monitoring of EBV-PCR after pediatric OLT is recommended to decrease the risk of PTLD by allowing early detection of EBV infection, which is then managed by decreasing immunosuppression and continuing intravenous ganciclovir.     

Posttransplantation lymphoproliferative disorder associated with OKT3 and decreased antiviral prophylaxis in pancreas transplant recipients

Between September 1994 and October 1995, we diagnosed and treated four cases of early onset posttransplantation lymphoproliferative disorder (PTLD) occurring within 62 days of pancreas transplantation. The development of PTLD was associated with both a significantly higher total muromonab-CD3 (OKT3) dose and a lack of ganciclovir/acyclovir prophylaxis, but it was not associated with the total dose of antithymocyte globulin or cytomegalovirus serostatus. All four patients were treated aggressively and survived without evidence of recurrent PTLD more than 1.5 years later. We conclude that the use of a high total dose of OKT3 puts pancreas transplant recipients at increased risk for early onset PTLD, while ganciclovir/acyclovir prophylaxis may help to prevent this disorder; however, if early onset PTLD does occur in these patients, aggressive therapy can lead to a favorable outcome.     

Self-inflicted intramyocardial injury with a sewing needle: a rare cause of pneumothorax

Ganciclovir susceptibilities and UL97 sequences were analyzed in 20 cytomegalovirus (CMV) isolates recovered from 15 bone marrow transplant recipients with active CMV infection after prophylaxis with acyclovir (group I; 12 isolates) or after acyclovir prophylaxis followed by ganciclovir therapy (group II; 8 isolates). All group I isolates were susceptible to ganciclovir. Five group II isolates were susceptible to ganciclovir, and 3 isolates (all from the same person) were resistant to ganciclovir (IC50 > 12 microM). Ganciclovir resistance UL97 mutations were found in 4 group II isolates, including a ganciclovir-susceptible isolate obtained from 1 patient after 41 days of therapy with ganciclovir and 3 ganciclovir-resistant isolates obtained from another patient after 73, 116, and 132 days of treatment with ganciclovir. Ganciclovir-resistant CMV isolates may emerge rapidly in bone marrow transplant recipients who are treated with ganciclovir after receiving prophylaxis with acyclovir.     

Strategies for the prevention of cytomegalovirus disease after marrow transplantation

The purposes of this review are to examine the epidemiology of disease due to cytomegalovirus (CMV) in recipients of autologous and allogeneic marrow transplants and to compare different antiviral regimens used for the prevention of such disease in recipients of allogeneic marrow transplants, with an emphasis on ganciclovir. In seven studies, ganciclovir reduced the incidence of CMV infection and disease after allogeneic marrow transplantation. In one study mortality after transplantation was reduced because of a decreased rate of CMV-related death among ganciclovir-treated patients. Ganciclovir was effective when given to all CMV-seropositive patients (prophylaxis) or to patients who were considered at high risk for CMV disease on the basis of a positive surveillance culture (early treatment). The effectiveness of ganciclovir for the prevention of CMV infection and disease is limited by drug-induced neutropenia. Experience with other antiviral agents, such as foscarnet, has been limited. Initial studies of the adoptive transfer of CMV-specific CD8+ cytotoxic T cells have been conducted. In short, ganciclovir is currently effective for the prevention of CMV disease in allogeneic marrow transplant recipients, but its usefulness is limited by neutropenia. Future studies must be aimed at confining the toxicity of ganciclovir to patients at the highest risk for CMV disease.     

A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients

BACKGROUND: Posttransplantation cytomegalovirus (CMV) infection remains a significant cause of morbidity in kidney transplant recipients. We performed a randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for CMV prophylaxis in a group of renal allograft recipients considered at high risk for CMV disease due to the use of OKT3 induction therapy. METHODS: A total of 101 recipients of cadaveric (83) and zero haplotype-matched live donor (18) kidney transplants were entered into the trial. A total of 22 D-R- patients received no prophylaxis. Twenty-seven D+R-, 29 D+R+, and 23 D-R+ patients were randomized to receive 3 months of either oral acyclovir (800 mg q.i.d.) or oral ganciclovir (1000 mg t.i.d.). Doses were adjusted according to the level of renal function. The D+R- patients were also given CMV immune globulin biweekly for 16 weeks. Surveillance blood cultures were obtained at transplantation, at months 1, 2, 3, and 6, and when clinically indicated. The primary study end points were time to CMV infection and disease the first 6 months after transplantation. RESULTS: The mean follow up was 14.4 months. Both agents were well tolerated, and no drug interruptions for toxicity occurred. CMV was isolated in 14 of 39 (35.9%) acyclovir-treated and 1 of 40 (2.5%) ganciclovir-treated recipients by 6 months (P=0.0001). Symptomatic CMV disease occurred in 9 of 14 (64%) of the acyclovir patients, two with tissue-invasive disease. Infection rates for acyclovir vs. ganciclovir, respectively, stratified by CMV serology were: D+R-, 54 vs. 0%, P=0.0008; D+R+, 43 vs. 6.6%, P=0.01; D-R+, 8.3 vs. 0%, P=NS. No patient developed CMV infection while taking oral ganciclovir, however three delayed infections occurred 2-7 months after finishing therapy. Each patient had been previously treated for acute rejection. CONCLUSIONS: Oral acyclovir provides effective CMV prophylaxis only for recipients of seronegative donor kidneys. Oral ganciclovir is a superior agent providing effective CMV prophylaxis for recipients of seropositive donor kidneys. Recipients who are treated for acute rejection are at risk for delayed CMV infection during the first posttransplantation year.     

Depression and the risk of coronary heart disease in the Normative Aging Study

BACKGROUND: Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). METHODS: This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). RESULTS: After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. DISCUSSION: In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.     

Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients

BACKGROUND: Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis. METHODS: Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6. RESULTS: No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005). CONCLUSIONS: An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.     

Human herpesvirus-6 meningoencephalitis in a recipient of an unrelated allogeneic bone marrow transplantation

BACKGROUND: Human herpesvirus-6 (HHV-6) has been implicated in bone marrow suppression, interstitial pneumonitis, and fatal meningoencephalitis in bone marrow transplant (BMT) recipients. METHODS: We describe the case of a woman with acute myeloid leukemia in second remission who developed febrile meningoencephalitis 8 months after a second unrelated BMT. RESULTS: Computed tomography and magnetic resonance images of the brain were nonspecific. Analysis of cerebrospinal fluid (CSF) revealed lymphocytosis and an increased protein level. Using polymerase chain reaction methods, HHV-6 was the only pathogen detected in CSF, peripheral blood mononuclear cells, and bone marrow. The patient was treated with ganciclovir and foscarnet for 3 months. All clinical manifestations resolved and HHV-6 polymerase chain reaction analysis of CSF became negative 40 days after the beginning of antiviral treatment. CONCLUSIONS: This observation strongly suggests that HHV-6 should be sought in BMT patients with neurological complications and that HHV-6 meningoencephalitis may respond to ganciclovir and foscarnet therapy.     

Autologous lymphokine-activated killer cell therapy of Epstein-Barr virus-positive and -negative lymphoproliferative disorders arising in organ transplant recipients

Lymphoreticular malignancies, collectively called posttransplant lymphoproliferative disorders (PTLD), eventually develop in 2-5% of organ transplant recipients. They frequently undergo regression when immunosuppression is reduced or stopped. This feature has been associated with a previous or de novo Epstein-Barr virus (EBV) infection. We herein describe immunotherapy with autologous lymphokine-activated killer (LAK) cells in seven patients with PTLD (four EBV-positive patients and three EBV-negative patients). Autologous peripheral blood mononuclear cells were obtained by leukapheresis, depleted of monocytes, and cultured in the presence of interleukin 2 for 10 to 11 days. A single dose of 5.2 x 10(9) to 5.6 x 10(10) LAK cells was given intravenously. Systemic interleukin 2 was not administered. The four patients with EBV+ PTLD had complete tumor regression; two of them developed controllable rejection. Three patients are well 13-16 months after treatment; the fourth patient died of pneumonia 41 days after infusion. Three patients with EBV- lymphomas had no response despite prior evidence that their tumors also were subject to immune surveillance. Two of these three patients died after being given other treatment, and the third patient has persistent tumor. In conclusion, autologous LAK cell infusion was effective for treatment of four EBV+ organ transplant recipients. LAK cell efficacy for three patients with EBV- PTLD was not evaluable under the management circumstances in which this treatment was utilized.     

Psychiatric diseases presenting as infectious diseases

BACKGROUND: Cytomegalovirus (CMV) disease is an important cause of organ transplant-related morbidity and mortality. During the last 5 years at our institution, prophylactic ganciclovir and hyperimmune globulin have been routinely administered to lung transplant recipients whenever the donor or the recipient was CMV antibody-positive. We sought to assess the efficacy of prophylaxis on viremia, CMV disease, and bronchiolitis obliterans syndrome (BOS). METHODS: A retrospective chart review of 61 consecutive lung transplants performed between recipients between January 1993 and August 1995 was performed. Fifty-six patients who survived at least 1 month were analyzed. Patients were considered at risk for CMV disease whenever pretransplant donor or recipient serology was positive. RESULTS: Fourteen of the 39 patients at risk (36%) had viremia while on prophylaxis. The rate of CMV disease was 13% during the first 6 months following transplantation. A donor whose CMV serology was positive appeared to increase the risk of BOS in a Cox regression model (relative risk=2.4; 95% confidence interval=0.86-6.74; p=0.0957). Neither age, CMV infection (viremia or a positive specimen from BAL), recipient's serology at the time of transplantation, or CMV disease was associated with BOS. None of these variables was associated with mortality on Cox regression analysis or univariate analysis. CONCLUSIONS: Administration of combination ganciclovir and hyperimmune globulin prophylactic therapy to lung transplant recipients at risk for CMV infection and disease is associated with a relatively low incidence of disease, which appears only after prophylaxis treatment with ganciclovir is completed. Ganciclovir prophylaxis does not prevent CMV viremia; however, viremia while on prophylaxis is not predictive of disease.     

Failure of ganciclovir prophylaxis to prevent allograft reinfection following orthotopic liver transplantation for chronic hepatitis B infection

The effect of ganciclovir prophylaxis on reinfection of hepatic allografts by hepatitis B virus (HBV) was studied in 26 patients undergoing orthotopic liver transplantation (OLT) for decompensated cirrhosis due to HBV. Patients were randomized to receive either ganciclovir (6 mg/kg/day intravenously for a total of 100 days) or acyclovir (10 mg/kg every 8 hours intravenously until discharged and then 800 mg orally every 6 hours) for a total of 100 days after OLT as part of a study of prophylaxis against cytomegalovirus infection. All patients received hepatitis B immunoglobulin (HBIG), 10,000 units intravenously, during the anhepatic phase, daily for the first 7 days, after OLT, and then every 4 weeks for 6 months, Seven of 12 (58%) patients in the ganciclovir group developed recurrent HBV, compared with 6/14 (46%) of the acyclovir group (nonsignificant). No significant difference was observed in time to recurrent HBV in the ganciclovir group (mean 13.2 months) compared to the acyclovir group (mean 11 months). Our results suggest that ganciclovir administered prophylactically for 100 days after OLT does not prevent or delay graft reinfection by HBV.     

Impact of high-dose oral acyclovir prophylaxis on cytomegalovirus (CMV) disease in CMV high-risk renal transplant recipients

Recent studies showed contradictory results concerning the efficacy of oral acyclovir in the prevention or amelioration of cytomegalovirus (CMV) disease after renal transplantation (TX). This study evaluated the incidence and severity of CMV disease within the first year after TX in high-risk renal transplant recipients (CMV-seropositive donor, seronegative recipient) treated prophylactically with oral acyclovir (800 to 3200 mg/day) over a period of 12 wk (ACY, N = 22), compared with high-risk patients randomly assigned as controls (CO, N = 10). Follow-up for CMV infection included serological determination of CMV-specific immunoglobulin G and immunoglobulin M antibodies, antigen detection in peripheral blood leukocytes (PP 65), shell vial culture (blood), and virus isolation/early antigen detection (urine). Severity of CMV disease was quantified by a scoring system for CMV-related symptoms. Nine patients (40.1%) in the acyclovir group and four patients (40%) in the control group developed CMV disease. Neither severity (ACY, 11.4 versus CO; 12.5 points score), nor duration of disease (ACY, 21 days; CO, 22 days), nor transplant function at the end of the observation period differed significantly. The onst of CMV disease was not delayed significantly in acyclovir-treated patients compared with controls (ACY, 47 +/- 34 days versus CO, 27 +/- 14 days after TX, not significant). Our results show no beneficial effect of oral acyclovir prophylaxis in CMV high-risk renal transplant recipients.     

Feline bone marrow transplantation: its use in FIV-infected cats

The use of autologous and allogenic bone marrow transplantations (BMT) in FIV-infected and uninfected cats is a novel therapy for feline hematopoietic diseases and retroviral infections. A total of 13 specific pathogen-free (SPF) cats received either autologous or allogenic BMT and seven of these cats were also infected with FIV before autologous or allogenic BMT. All BMT recipients received total body irradiation of 900 cGy just before BMT. Two FIV-infected and four uninfected cats received autologous uninfected BM cells cryopreserved before BMT. Five infected and two uninfected cats received BM cells from allogenic uninfected donors (RBC-, MHC-, and cross-matched). MHC-matching was based on mixed leucocyte reaction (MLR) and the donor-recipient combination which was compatible by MLR analysis, was used in this study. Recipients were monitored for hematology, immunology, virology, and clinical signs. All FIV-infected and uninfected recipients of autologous BMT had complete engraftment with minimal complications. Uninfected recipients of allogenic BMT had a more severe clinical episode with slower rate of engraftment. None of these BMT groups had mortality. In contrast, only two of the five infected recipients of allogenic BMT survived for a significant period of time (23 and 50 weeks) and rest of the cats succumbed to transfusion reactions. Both infected BMT groups had persistent CD4/CD8 inversion, low CD4+ cell counts, and FIV infection of engrafted peripheral blood mononuclear cells (PBMC). Overall, successful autologous and allogenic BMTs were performed in FIV-free cats. All infected recipients of autologous BMT had compete engraftment and are currently alive, with thelongest survival time being over 1 year. Thus, BMT in combination with antiviral drug therapies may be an alternative therapy against retroviral infection.     

Evolution of the Sry genes

Cytomegalovirus (CMV) infection is a major cause of morbidity and occasionally of mortality in immunosuppressed allograft recipients. At the University of Cincinnati Medical Center, ganciclovir has been administered for the prevention of CMV infection since July 1992. Forty-six recipients of cadaveric renal allografts (Group I) received ganciclovir at a dose of 2.5 or 5 mg/kg/day (adjusted for renal function) for 14-21 days, during induction treatment and during antirejection treatment with monoclonal or polyclonal antilymphocyte preparations. In this retrospective study, these 46 patients were compared with 77 recipients of cadaveric renal allografts transplanted prior to July 1992 (Group II) for the prevalence, severity and time of CMV occurrence after transplantation. CMV diagnosis was based on clinical evaluation and was confirmed by blood cultures, CMV antigen immunofluorescence assay and/or histology. Patients were stratified according to CMV serology (+) or (-) in donor and recipient. CMV infection developed in 16 of 46 (35%) patients in Group I vs. 27 of 77 (35%) patients in Group II (p = 0.97). A total of 25 episodes of CMV infection occurred in Group I compared to 44 in Group II (p = 0.76). CMV infection was diagnosed an average of 97.4 days after transplant in Group I compared to 48.3 days in Group II (p = 0.0003). Tissue-invasive CMV infection occurred in 3 patients in Group I (19%) vs. 12 in Group II (44%) (p = 0.5). In conclusion, ganciclovir prophylaxis resulted in a delayed onset of clinical CMV infection with a trend towards less severe infection in patients treated with antilymphocyte antibody preparations.     

Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus infections after heart transplantation

Cytomegalovirus (CMV) infection is associated with an increased incidence of other opportunistic infections in organ transplant recipients. Whether this is related to immunomodulating effects of CMV or independent of CMV but associated with a host risk factor common to both infections is unclear. The purpose of this study was to determine whether the reduction in CMV infections seen with prophylactic ganciclovir treatment after heart transplantation is associated with a reduced incidence of other opportunistic infections. Of 149 patients prospectively enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of ganciclovir to prevent CMV disease, 74 patients enrolled at this center (33 control and 41 ganciclovir-treated) were retrospectively identified. All received prophylactic OKT-3 and standard 3 drug maintenance immunosuppressive therapy. Actuarial survival and rejection rates and incidence of opportunistic infections (bacterial, fungal, and protozoal) for the 2 treatment groups were determined and compared using Cox-Mantel analysis. CMV disease occurred 2.5 times more frequently in the control group. There were no significant differences in survival or rejection rates nor in bacterial or protozoal infection incidence between the 2 groups. Bacterial infections occurred in 54% of control and 39% of ganciclovir-treated patients (P = 0.18). There were significantly fewer fungal infections in the ganciclovir-treated group (7% vs. 27%, P = 0.0071). CMV and fungal infections were both significantly reduced in patients who received ganciclovir prophylaxis. This suggests that active CMV disease may be causally associated with the development of opportunistic fungal infections.     

Magnetic resonance imaging in pseudotumor cerebri

Post-transplantation lymphoproliferative disorders (PTLD) are a complication of immunosuppressed transplant recipients, and their incidence is reported to be 20-120 times greater than the rate in the general population. After kidney transplantation, PTLD more likely arise within the renal transplant fossa. Radiological patterns of these forms are presented and discussed, according to a review of the literature, and illustrated by cases from our institution. Ultrasound plays an essential role in the early diagnosis of PTLD by detecting a urinary obstruction associated with adenopathy or an ill-defined mass not previously seen. However, in the case of an inconclusive US examination, CT or MRI should be performed to confirm the presence of a mass. Both techniques are useful in evaluating the extension of the process within the transplantation fossa; MRI seems more accurate and can be used for the follow-up, especially after reduction in immunosuppressive therapy without transplant removal.     

Emergency medicine: the Italian experience

BACKGROUND: Studies using tacrolimus and corticosteroids or the combination of cyclosporine, mycophenolate mofetil, and corticosteroids have been shown to reduce the incidence of biopsy-proven acute rejection episodes in cadaveric kidney recipients compared with cyclosporine-based immunosuppression. The current study is a retrospective analysis of our experience with tacrolimus combined with mycophenolate mofetil and steroids as primary immunosuppression for kidney transplant recipients. METHODS: In a retrospective analysis, 72 patients who received primary therapy with tacrolimus, mycophenolate mofetil, and corticosteroids (triple therapy) were compared with a control group of 98 kidney recipients who received tacrolimus and corticosteroids (double therapy). RESULTS: There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the triple therapy group (8.2%) compared with the double therapy group (21%; P=0.003). One-year patient and graft survival did not differ between groups. The incidence of posttransplant diabetes mellitus was 18% and 21% in the triple and double therapy groups, respectively. Leukopenia and gastrointestinal side effects were the most common cause for discontinuation of mycophenolate mofetil. CONCLUSIONS: The combination of tacrolimus with mycophenolate mofetil and corticosteroids is more effective at preventing early acute rejection than tacrolimus and corticosteroids alone. The use of mycophenolate mofetil was associated with a higher incidence of leukopenia and diarrhea, often leading to discontinuation of the drug.