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.     

The impact of sacral root anatomy on selective electrical stimulation for bladder evacuation

The present study was conducted to examine the clinicopathological features of recurrent IgA nephropathy (IgAN) following renal transplantation. Serial renal biopsies were performed regularly at 0-hour, 1-hour and 2-hours, and 39 episode biopsies were carried out when patients had increased serum creatinine levels and proteinuria. In 49 renal allograft recipients with IgAN, 12 patients were proved to be recurrent IgAN (24.5%). There was a significantly increased five- and ten-year risk of graft loss in the renal allograft recipients with biopsy-proved recurrent IgAN. Graft survival in 49 renal allograft recipients with IgAN was worse (68.8% at 5 years and 40.4% at 10 years) than that in 997 whole transplants (80.7% at 5 years, and 67.7% at 10 years). We found significant differences in the prevalence of HLA-DR4 (66.7%) and BW35 (25%) in the renal allograft recipients with recurrent IgAN when compared with normal healthy subjects. The renal allograft recipients with recurrent IgAN had a high incidence of proteinuria (8/12), hypertension (9/12) and renal dysfunction of less than 50 ml/min (7/12). Mean hemodialysis duration before renal transplantation in recurrent IgAN transplants was 12.5 months, which was shorter than in those without recurrent IgAN. Histopathological studies revealed that renal lesions due to IgAN frequently appeared in the renal allograft recipients with recurrent IgAN. Taken together, these findings suggest that donor-recipient matching may be carefully reconsidered, and recurrent IgAN after renal transplantation must be treated with effective immunosuppressive therapy.     

Posttransplant hemolytic uremic syndrome in adult retransplanted kidney graft recipients: advantage of FK506 therapy?

BACKGROUND: Posttransplant hemolytic uremic syndrome (pHUS) is a rare but severe disorder that confers a poor prognosis on an allograft due to thrombotic microangiopathy. Immunosuppression with cyclosporine (CsA) is implicated as a significant risk factor for the development of pHUS. In early reports, it was hypothesized that immunosuppression with FK506 (tacrolimus) would avoid the development of pHUS. However, this initially supposed beneficial effect remains controversial, because pHUS associated with tacrolimus therapy has been published in some later case reports. This article aims to further evaluate FK506 with respect to the development and resolution of pHUS. METHODS: We describe the course of seven adult kidney graft recipients with pHUS, treated with FK506 either as initial immunosuppression for retransplantation or after discontinuation of CsA for resolution of pHUS. Work-up for pHUS was initiated when certain clinical features, such as hemolytic anemia, thrombocytopenia, and deterioration of graft function, were found. The diagnosis was confirmed by histologic examination of a renal allograft biopsy specimen (thrombotic microangiopathy). With the onset of pHUS, additional plasma exchange was performed in all patients. RESULTS: Two patients suffered from end-stage renal disease due to primary HUS and had a history of recurrent pHUS in previous renal transplants. In both patients, the attempt to regraft was only made because of the early optimistic reports using FK506. Despite initial FK506 therapy, both recipients developed pHUS again, leading to loss of graft function. Two additional kidney graft recipients with primary renal failure other than HUS also received FK506 as initial immunosuppression. One of them (loss of the first kidney graft due to CsA-induced pHUS) was successfully treated with FK506 for his second renal transplant. The other recipient, a patient in whom de novo pHUS had occurred in the first graft despite initial therapy with FK506, was treated with CsA for his second graft and again developed pHUS. The latter process, however, could be reversed by a switch to steroids and azathioprine. In all three patients regrafted for reasons other than pHUS, development of de novo pHUS was treated by CsA withdrawal and a switch to FK506; this approach was effective in two patients. CONCLUSION: Our results demonstrate that three of seven renal allograft recipients benefited from FK506 therapy for prevention or resolution of pHUS. Treatment or prophylaxis with FK506 can be considered advantageous in some patients with de novo pHUS, but FK506 fails to prevent recurrent pHUS in patients with primary HUS.     

Ototoxicity of amikacin

Amikacin was used in 77 treatment courses at a dosage of >/=7.5 mg/kg every 8 h, and patients were monitored for ototoxicity by following serial audiograms, serum creatinine, and amikacin blood levels. Patients were leukopenic (58), were infected by gentamicin-resistant organisms (11), or had cystic fibrosis (8). Three patients developed tinnitus, but none had vertigo or nystagmus. Of 55 courses with pre- and post-treatment audiogram, 13 (24%) were associated with development of high-frequency hearing loss, which was usually bilateral. No patient had conversational hearing loss, and audiograms reverted to normal in three patients. Onset of cochlear damage occurred in one patient after therapy was stopped. The group with high-tone hearing loss, in comparison to the group without audiographic changes, received a larger mean total dose (24 versus 9.6 g), were treated for a longer duration (19 versus 9 days), and more frequently had previous aminoglycosides. Fifty-seven percent of patients with a "peak" serum level exceeding 32 mug/ml and 55% of patients with "trough" levels exceeding 10 mug/ml developed cochlear damage. There was no difference between the groups in age, body weight, previous cochlear damage, renal disease before or during therapy, or average daily dose. Both monitoring of blood levels and limiting duration of therapy may prevent amikacin ototoxicity.     

Hearing loss after erythromycin therapy

We describe the case of a patient who developed bilateral loss of hearing during intravenous treatment with erythromycin. Predisposing factors may have been reduced renal and hepatic function and treatment with diuretics and aminoglycosides. Recovery was late, but hearing was probably restored to almost pre-treatment level. Patients receiving high doses of erythromycin should, as a routine, be questioned about hearing loss and tinnitus.     

Parvovirus B19 infection-related complications in renal transplant recipients: treatment with intravenous immunoglobulin

BACKGROUND: Chronic red cell aplasia can develop in immunocompromised patients including transplant recipients infected with parvovirus B19 (PV B19). Renal involvement with PV B19 infection is not well-recognized. METHODS: We diagnosed erythroid hypoplasia associated with PV B19 infection in three renal transplant recipients; one of them developed de novo collapsing glomerulopathy. These patients were treated with intravenous immunoglobulin (IVIG). RESULTS: In two patients, anemia responded promptly to IVIG therapy. One of them had recurrence of anemia that responded to a second course of IVIG. Despite IVIG treatment, persistent infection with PV B19, recurrent anemia, and de novo collapsing glomerulopathy leading to allograft failure developed in the third patient, who had received the most intense immunosuppression. CONCLUSIONS: These findings indicate that PV B19 infection in transplant recipients can cause chronic red cell aplasia that generally responds to IVIG therapy. In some patients, particularly those who are heavily immunosuppressed, infection may persist despite treatment. As the cellular receptor for PV B19 is expressed in the kidney, persistent infection may result in development of glomerulopathies in these patients.     

Prognosis after primary renal transplant failure and the beneficial effects of repeat transplantation: multivariate analyses from the United States Renal Data System

BACKGROUND: Survival of transplant recipients after primary renal allograft failure has not been well studied. METHODS: A cohort of 19,208 renal transplant recipients with primary allograft failure between 1985 and 1995 were followed from the date of allograft loss until death, repeat transplantation, or December 31, 1996. The mortality, wait-listing, and repeat transplantation rates were assessed. The mortality risks associated with repeat transplantation were estimated with a time-dependent survival model. RESULTS: In total, 34.5% (n=6,631) of patients died during follow-up. Of these deaths, 82.9% (n=5,498) occurred in patients not wait-listed for repeat transplantation, 11.9% (n=789) occurred in wait-listed patients, and 5.2% (n=344) occurred in second transplant recipients. Before repeat transplantation, the adjusted 5-year patient survival was 36%, 49%, and 65% for type I diabetes mellitus (DM), type II DM, and nondiabetic end-stage renal disease, respectively (P<0.001; DM vs. nondiabetics). The adjusted 5-year patient survival was lower in Caucasians (57%, P<0.001) compared with African-Americans (67%) and other races (64%). The 5-yr repeat transplantation rate was 29%, 15%, and 19%, whereas the median waiting time for a second transplant was 32, 90, and 81 months for Caucasians, African-Americans, and other races, respectively (P<0.0001 each). Repeat transplantation was associated with 45% and 23% reduction in 5-year mortality for type I DM and nondiabetic end-stage renal disease, respectively, when compared with their wait-listed dialysis counterparts with prior transplant failure. CONCLUSIONS: The loss of a primary renal allograft was associated with significant mortality, especially in recipients with type I DM. Repeat transplantation was associated with a substantial improvement in 5-year patient survival. Recipients with type I DM achieved the greatest proportional benefit from repeat transplantation.     

A randomized comparative study on the safety and efficacy of clarithromycin and erythromycin in treating community-acquired pneumonia

BACKGROUND: Clarithromycin, a new macrolide, has distinct microbiological and pharmacokinetic advantages compared with erythromycin. This study was designed to compare the safety and efficacy of clarithromycin and erythromycin in the treatment of community-acquired pneumonia. METHODS: Forty adult patients, diagnosed with community-acquired pneumonia, were randomly arranged to received either clarithromycin 250 mg twice daily (20 patients) or erythromycin 500 mg four times daily (20 patients), over a period of 14 days each. RESULTS: There were no statistically significant differences between the two groups in terms of clinical cure (65% for clarithromycin, 65% for erythromycin), clinical success (clinical cure and improvement: 95% for clarithromycin, 90% for erythromycin) and radiological response (95% for clarithromycin, 90% for erythromycin). However, adverse effects, mainly gastrointestinal, were significantly higher among patients treated with erythromycin than among patients treated with clarithromycion (p < 0.05). CONCLUSIONS: These results demonstrate that clarithromycin 250 mg twice daily is at least as effective as erythromycin 500 mg four times daily for the treatment of community-acquired pneumonia, and is much better tolerated.     

Tularemia presenting as community-acquired pneumonia. Implications in the era of managed care

A case of pleuropulmonary tularemia was diagnosed by sputum culture and serologic studies in a patient who did not have classic epidemiological risks for tularemia. The patient had atypical pneumonia when initially seen and his condition slowly improved with antibiotic therapy that included erythromycin lactobionate. The diagnosis of tularemia was delayed because the gram-negative rod isolated from the patient's sputum was initially not speciated in an effort to reduce laboratory costs.     

Positive selection driving the evolution of a gene of male reproduction, Acp26Aa, of Drosophila: II. Divergence versus polymorphism

BACKGROUND: Sirolimus, a novel immunosuppressant that inhibits cytokine-driven cell proliferation and maturation, prolongs allograft survival in animal models. After a phase I trial in stable renal transplant recipients documented that cyclosporine and sirolimus have few overlapping toxicities, we conducted an open-label, single-center, phase I/II dose-escalation trial to examine the safety and efficacy of this drug combination. METHODS: Forty mismatched living-donor renal transplant recipients were sequentially assigned to receive escalating initial doses of sirolimus (0.5-7.0 mg/m2/day), in addition to courses of prednisone and a concentration-controlled regimen of cyclosporine. We conducted surveillance for drug-induced side effects among sirolimus-treated patients and compared their incidence of acute rejection episodes as well as mean laboratory values with those of a historical cohort of 65 consecutive, immediately precedent, demographically similar recipients treated with the same concentration-controlled regimen of cyclosporine and tapering doses of prednisone. RESULTS: The addition of sirolimus reduced the overall incidence of acute allograft rejection episodes to 7.5% from 32% in the immediately precedent cyclosporine/prednisone-treated patients. At 18- to 47-month follow-up periods, both treatment groups displayed similar rates of patient and graft survival, as well as morbid complications. Although sirolimus-treated patients displayed comparatively lower platelet and white blood cell counts and higher levels of serum cholesterol and triglycerides, sirolimus did not augment the nephrotoxic or hypertensive proclivities of cyclosporine. The degree of change in the laboratory values was more directly associated with whole blood trough drug concentrations than with doses of sirolimus. CONCLUSIONS: Sirolimus potentiates the immunosuppressive effects of a cyclosporine-based regimen by reducing the rate of acute rejection episodes.     

Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia

BACKGROUND: Switch therapy is defined as the early transition from intravenous to oral antibiotics during treatment of infection. This study was designed to evaluate the clinical outcome and length of stay of hospitalized patients with community-acquired pneumonia treated with an early switch from intravenous to oral third-generation cephalosporins. METHODS: Patients with a new roentgenographic pulmonary infiltrate and at least two symptoms (cough, fever, or leukocytosis) were enrolled in this study and treated with intravenous ceftizoxime sodium (1 g every 12 hours) or ceftriaxone sodium (1 g every 24 hours). Patients were switched to oral cefixime (400 mg every 24 hours) as soon as they met the following criteria: (1) resolution of fever; (2) improvement of cough and respiratory distress; (3) improvement of leukocytosis; and (4) presence of normal gastrointestinal tract absorption. RESULTS: Of the 120 patients enrolled, 75 (62%) had clinical data evaluated. Long-term follow-up showed that 74 patients (99%) were cured; one patient required readmission for further intravenous therapy. Mean duration of hospital stay was 4 days. CONCLUSIONS: This investigation demonstrated that an early switch to oral cefixime may be reasonable in hospitalized patients with community-acquired pneumonia who have already shown a good clinical and laboratory response to therapy with intravenous third-generation cephalosporins. This approach is clinically effective and minimizes hospital stay.     

Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group

This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.     

Transcriptional regulation of aquaporin-2 water channel gene by cAMP

In patients awaiting heart transplantation, end-stage disease of a second organ may occasionally require consideration of simultaneous multiorgan transplantation. Outcome statistics in multiorgan transplant recipients are needed to define optimal utilization of scarce donor resources. Incidence of cardiac allograft rejection, actuarial recipient survival, and cardiac allograft rejection-free survival were evaluated in 82 recipients of 84 simultaneous heart and kidney transplants. Twenty-three of the 82 dual-organ recipients have died with 1, 6, 12, and 24-month actuarial survival rates of 92%, 79%, 76%, and 67%, respectively. The actuarial survival rates in the heart-kidney recipients were similar to those observed in 14,340 isolated heart recipients (United Network for Organ Sharing Scientific Registry) during the same period (92%, 86%, 83%, and 79%, respectively; P=0.20). Clinical data on all episodes of treated rejection in either organ and on immunosuppressive regimens were available on 56 patients; 48% of these patients have had no rejection in either organ, 27% experienced heart rejection alone, 14% experienced kidney rejection alone, and 11% had both heart and kidney allograft rejection. Heart allograft rejection was less common in heart-kidney recipients, as compared with isolated heart transplant recipients; 0, 1, and > or = 2 treated cardiac allograft rejection episodes occurred in 63%, 20%, and 18% of heart-kidney recipients compared with 46%, 27%, and 28% of 911 isolated heart recipients reported by Transplant Cardiologists' Research Database (P=0.02). The rejection-free survival rates at 1, 3, and 6 months were 88%, 74%, and 71% in the double-organ recipients, as compared with 66%, 44%, and 39%, respectively, in the single-organ recipients. Compared with isolated heart transplantation, combined heart-kidney transplantation does not adversely affect intermediate survival and results in a lower incidence of treated cardiac allograft rejection. The findings suggest that combined heart-kidney transplantation may be an acceptable option in a small subset of potential heart transplant recipients with severe renal dysfunction.     

Efficacy and safety of low molecular weight heparin in renal transplantation

BACKGROUND: Deep venous thrombosis (DVT) is a common problem with potentially devastating results in patients undergoing major surgical procedures. Certain renal transplant recipients are particularly at risk for allograft loss as a consequence of renal vein and artery thrombosis. Over the past few years, low molecular weight heparin has been well established as an accepted modality of treatment and prophylaxis of DVT. The efficacy and safety of low molecular weight heparin in the prophylaxis of DVT following renal transplantation in adults has not previously been reported. METHODS: Dalteparin was administered to 120 adult renal transplant recipients postoperatively at the Oregon Health Sciences University. RESULTS: No patient developed allograft arterial or venous thrombosis. One patient developed subclavian vein thrombosis. No bleeding complications were encountered, and side effects were very minimal. CONCLUSION: Prophylaxis with dalteparin is an effective and safe modality for the prevention of thrombosis in adult patients undergoing renal transplantation.     

The great success of Asian kidney transplant recipients

BACKGROUND: Little has been written about allograft survival in non-African-American minority groups. We examine the success of kidney transplantation in 1900 Asian recipients. METHODS: Data from 42,252 cadaveric and 16,115 live donor kidney transplant recipients were monitored from the United Network for Organ Sharing Scientific Renal Transplant Registry from 1991 through 1996. RESULTS: Asian recipients exhibited the highest cadaveric allograft survival rates (89% 1-year and 83% 3-year survival) and the longest mean allograft half-life (18 years). Asian women had the highest mean graft half-life (23 years). Asians were less likely to be broadly sensitized and had a high incidence of IgA nephropathy causing end-stage renal disease. Although it has been suggested that their low body weights may help explain the excellent allograft outcome, Asians exhibited superior graft survival rates even when compared with low body weight recipients of other races. CONCLUSION: Asian renal allograft recipients, particularly Asian females, have the highest allograft survival rates of all racial groups.     

Clinical efficacy of dirithromycin in patients with bacteremic pneumonia

Dirithromycin is a new macrolide antimicrobial drug with a long half-life (44 hours) that reaches high tissue concentrations, thus permitting once-daily oral dosing and shorter courses of therapy. Soon after absorption, dirithromycin enters the tissue so rapidly that serum concentrations are comparatively low. It could be hypothesized that these low serum levels could endanger the outcome in patients with bacteremic pneumonia. We reviewed the database on dirithromycin pneumonia (consisting of 1108 patients randomized to receive dirithromycin or erythromycin in two double-masked trials) to ascertain its efficacy in patients with community-acquired pneumonia and concomitant bacteremia. Fourteen (2.5%) of 555 dirithromycin-treated patients and 10 (1.8%) of 553 erythromycin-treated patients had bacteremia. A favorable clinical response posttherapy was observed in 92.3% and 88.9% of these patients with a response assigned, respectively. Overall, favorable response rates were comparable between the two groups in the bacteremic subsets: patients with pneumococcal bacteremia, patients with nonbacteremic pneumococcal pneumonia, and all patients enrolled with acute pneumonia who had a posttherapy clinical response. In the treatment of patients with mild or moderate community-acquired pneumonia, including those with unsuspected and incidental bacteremia, dirithromycin is an effective macrolide antimicrobial drug.     

A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group

BACKGROUND: Tacrolimus (FK506), a macrolide molecule that potently inhibits the expression of interleukin 2 by T lymphocytes, represents a potential major advance in the management of rejection following solid-organ transplantation. This randomized, open-label study compared the efficacy and safety of tacrolimus-based versus cyclosporine-based immunosuppression in patients receiving cadaveric kidney transplants. METHODS: A total of 412 patients were randomized to tacrolimus (n=205) or cyclosporine (n=207) after cadaveric renal transplantation and were followed for 1 year for patient and graft survival and the incidence of acute rejection. RESULTS: One-year patient survival rates were 95.6% for tacrolimus and 96.6% for cyclosporine (P=0.576). Corresponding 1-year graft survival rates were 91.2% and 87.9% (P=0.289). There was a significant reduction in the incidence of biopsy-confirmed acute rejection in the tacrolimus group (30.7%) compared with the cyclosporine group (46.4%, P=0.001), which was confirmed by blinded review, and in the use of antilymphocyte therapy for rejection (10.7% and 25.1%, respectively; P<0.001). Impaired renal function, gastrointestinal disorders, and neurological complications were commonly reported in both treatment groups, but tremor and paresthesia were more frequent in the tacrolimus group. The incidence of posttransplant diabetes mellitus was 19.9% in the tacrolimus group and 4.0% in the cyclosporine group (P<0.001), and was reversible in some patients. CONCLUSIONS: Tacrolimus is more effective than cyclosporine in preventing acute rejection in cadaveric renal allograft recipients, and significantly reduces the use of antilymphocyte antibody preparations. Tacrolimus was associated with a higher incidence of neurologic events, which were rarely treatment limiting, and with posttransplant diabetes mellitus, which was reversible in some patients.     

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.     

Sarcomas in organ allograft recipients

In a review of 8724 de novo malignancies that occurred in 8191 organ allograft recipients sarcomas were 7.4% of cancers. Kaposi's sarcoma (KS) made up 5.7%, and other sarcomas (OS) 1.7% a much higher proportion than in the general population. KS was most common in Arab, black, Italian, Jewish, or Greek patients. In 60% of patients with KS the lesions were confined to the skin and/or oropharynx while 40% involved internal organs and/or lymph nodes. Complete remissions following various treatments occurred in 53% of the former group and 27% of the latter. In both groups 32% and 60% of remissions, respectively, occurred when the only treatment was reduction or cessation of immunosuppressive therapy. However, this treatment caused impaired function or allograft loss from rejection in 22 of 34 kidney recipients. Recurrent KS occurred in 5% of patients in remission when immunosuppressive therapy was resumed. Nine of 114 patients (8%) tested for human immunodeficiency virus were positive. Most OS arose in internal organs or soft tissues. The major types were fibrous histiocytoma (20 patients), leiomyosarcoma (15), fibrosarcoma (12), rhabdomyosarcoma (9), hemangiosarcoma (8), undifferentiated sarcoma (7) and mesothelioma (6). Several unusual features were noted. Remarkably, 10 of 105 (10%) sarcomas occurred adjacent to or in a renal (6) or hepatic (4) allograft. Leiomyosarcomas are rare in children, yet 5 of 15 (33%) occurred in pediatric patients. Three hemangiosarcomas occurred in forearms at sites of arteriovenous fistulas used for pretransplant hemodialysis access. One leiomyosarcoma and one fibrosarcoma occurred in previously irradiated areas. One patient with mesothelioma had a history of asbestos exposure and two others had possible exposure.