Orthopaedic procedures and prognosis in hemophilic patients who are seropositive for human immunodeficiency virus

Thirty patients who had hemophilia and were seropositive for the human immunodeficiency virus were evaluated. The preoperative CD4 lymphocyte count was decreased to an average of 336 x 10(9) per liter (range, 27 to 708 x 10(9) per liter). After twenty-six orthopaedic operations in patients who had no previous bacterial infection, a nosocomial infection (cellulitis in the forearm, at the site of an intravenous catheter) developed in only one patient, but five patients had an abnormal postoperative fever that was not accompanied by the expected increase in the white blood-cell count. The preoperative CD4 lymphocyte count was significantly reduced in the patients who had an abnormal elevation in body temperature (p less than 0.004). The functional result or outcome after operation was similar to that in hemophilic patients treated before 1982. Subsequent progression of infection with the human immunodeficiency virus, as determined by the CD4 lymphocyte count and the Walter Reed classification system, occurred in most patients. Acquired immunodeficiency syndrome was diagnosed in six patients. A more rapid progression to acquired immunodeficiency syndrome was seen in the patients who had a lower CD4 lymphocyte count preoperatively. Preoperative evaluation of the CD4 lymphocyte count and the response to intradermal skin-test antigens in patients who are at risk for infection postoperatively provides additional information concerning immunological competence. With these data, the possible risk of infection in patients who are seropositive for the human immunodeficiency virus can be estimated more accurately.     

Knee arthroplasty in hemophilic arthropathy

Twenty-three total knee arthroplasties in 15 patients with severe hemophilia were performed between February 1974 and September 1988. Thirteen patients had Factor VIII deficiency and two had Factor IX deficiency. The mean followup period was 7.5 years, with a minimum of 4 years for patients who were alive (eight) at the time of this review. Seven patients had died before this report, and all were seropositive for the human immunodeficiency virus. Using the Hospital for Special Surgery knee scoring system, the result was excellent in one knee, good in three, fair in two, and poor in 17. One patient was seropositive for the human immunodeficiency virus at the time of the index procedure, and 12 were seropositive at the most recent followup; the human immunodeficiency status of three patients was unknown. There were two early and two late deep infections, all in patients who were seropositive for the human immunodeficiency virus. The most recent postoperative radiographs for all knees were reviewed using the Knee Society radiographic scoring system. Ten femoral components were well fixed, 11 were possibly loose, and two were probably loose. Eight tibial components were well fixed, 10 possibly loose, three probably loose, and two definitely loose. One knee had been revised for aseptic loosening. There are few published studies of the long term results of total knee arthroplasties in patients with hemophilia. In this series of 23 knees, there was a high rate of loosening and infection. Total knee arthroplasty may be a useful treatment for the relief of pain attributable to end stage hemophilic arthropathy, but there is a high rate of complications, especially in patients who are seropositive for the human immunodeficiency virus.     

Epidural blood patch in the HIV-positive patient. Review of clinical experience. San Diego HIV Neurobehavioral Research Center.

To characterize the natural history of autologous epidural blood patch (EBP) in human immunodeficiency virus (HIV)-seropositive patients, records from an ongoing longitudinal study of the neuropsychological manifestations of HIV infection were retrospectively reviewed. Of 252 participants (218 HIV-seropositive, 34 HIV-seronegative) who underwent at least one diagnostic lumbar puncture, 9 (7 seropositive, 2 seronegative) required EBP for post-dural puncture headache. After EBP, 6 of the seropositive subjects underwent serial neuropsychological evaluations over periods ranging from 6 to 24 months; none of these six subjects had a decline in neurocognitive performance or other adverse neurologic or infectious sequelae. We were unable to identify morbidity attributable to EBP in the HIV-seropositive patient followed for as long as 2 yr.     

Incidence and morbidity of cytomegalovirus disease associated with a seronegative recipient receiving seropositive donor-specific transfusion and living-related donor transplantation. A multicenter evaluation

This retrospective study was conducted to identify the frequency of cytomegalovirus (CMV) disease in seronegative recipients of donor-specific transfusion (DST) and living-related donor (LRD) kidneys from seropositive donors. A total of 151 LRD transplants (TX) were performed at six transplant centers over a 3-year period. A total of 33 patients were identified as having been seronegative (pre-TX) for CMV, yet they had DST and a TX from a seropositive LRD. Of these patients, 12 (36.4%) seroconverted within the first 6 months post-TX and developed clinical CMV disease. Additional patients seroconverted, but did not have evidence of clinical disease and were not tested further. All TX centers, with the exception of one, had seronegative patients that became ill after receiving a seropositive DST/LRD TX. Six patients manifested their disease as a febrile illness with leukopenia and liver enzyme elevations, four had pneumonitis, and two developed CMV ulcerations of the colon (one of whom died from resultant sepsis). Of the 36 seronegative patients who received seronegative DST/LRD TX none became ill with CMV disease. Of the 72 seropositive patients who received DST/LRD TX, only 2 (2.8%) developed CMV illness (one, seropositive into seropositive, the other, seronegative into seropositive). Of the 33 seronegative patients receiving seropositive DST/LRD TX, 17 received antilymphocyte preparations (ALP), and 8 of these became ill (47.1%). Of 16 patients not receiving ALP, 5 (31.3%) developed clinical CMV illness. Of the 33 patients who were identified as having been seronegative for CMV yet received seropositive DST/LRD TX, the 12 who did develop CMV illness had two graft losses, one death, and a serum creatinine for the remaining 9 patients of 2.3 +/- 1.6 at last follow-up. The remaining 21 patients who developed no illness had a serum creatinine of 1.3 +/- 0.6 with no graft losses at the last follow-up. This evidence suggests that a prospective TX recipient who is seronegative for CMV who receives DST/LRD TX from a seropositive family member has a significant risk for developing morbidity related to clinical CMV illness.     

HIV-1 infection among heterosexual attenders at a sexually transmitted diseases clinic in Durban

In a study of 2,682 selected attenders at a sexually transmitted diseases (STD) clinic for blacks in Durban, antibodies to human immunodeficiency virus type 1 (HIV-1) were detected in 63 (2.4%)--30 of 937 women (3.2%) and 33 of 1,745 men (1.9%). Women aged 15-19 years (P = 0.002) were at greater risk of HIV-1 infection than women of other age groups. Among men, HIV-1 seropositivity was associated with genital ulcer disease (GUD) (P = 0.007) and donovanosis (granuloma inguinale) (P = 0.02). Among seropositive men with donovanosis the probability of HIV-1 infection increased as the duration of lesions increased. When HIV-1 seropositive women were compared with a subgroup of 73 seronegative women with GUD, inflammatory cytological changes were associated with antibodies to HIV-1 (P = 0.02). Among women overall, HIV-1 seropositivity was associated with previous syphilis (P = 0.03). In men herpes zoster (P = 0.04) and in women lymphadenopathy (P = 0.002) accounted for HIV-1 seropositivity in patients with medical complaints. HIV-1 seropositivity in men with gonorrhoea and genital warts was less than in men without gonorrhoea (P = 0.001) and genital warts (P = 0.03). These results support the causal hypothesis of HIV transmission whereby mucosal discontinuity acts as a portal of entry for the virus. GUD and cervical inflammation secondary to STDs in seronegative subjects may facilitate HIV transmission. The relative risk of various STDs are probably dependent upon the duration of epithelial damage and exposure to HIV-1.     

Decreasing the Epstein-Barr virus load by adjusting the FK506 blood level

To prevent post-transplant lymphoproliferative disease (PTLD), the viral load must be diminished before the symptoms of Epstein-Barr virus (EBV) infection appear. Twenty-three consecutive liver transplant recipients were entered into our study to identify the characteristics of post-transplant EBV-infected patients and to clarify the correlation between the FK506 blood level and EBV load. After transplantation, EBV-DNA appeared more frequently in patients who had been seronegative before transplantation than in seropositive patients (10/13 versus 1/10; P=0.0014). As for rejection, resistance to steroid pulse therapy, and FK506 trough level, there were no significant differences between patients with and without EBV infection. In patients with primary EBV infection after transplantation, there was a strong correlation ( r=0.681) between the FK506 level and the viral load. In liver transplant recipients, especially in those seronegative for EBV, it is necessary to check the viral load by polymerase chain reaction (PCR) carefully after liver transplantation, before any symptom appears.     

Cytomegalovirus as a risk factor in living-related renal transplantation. A prospective study.

Forty-four living-related donor kidney (LRD) recipients (19 HLA-identical and 25 haploidentical) were followed prospectively to determine the posttransplant incidence and sequelae of cytomegalovirus (CMV) infection as they relate to the CMV status of recipients and donors. CMV titers were measured in all patients before transplantation by an immunofluorescent assay (IFA). Recipients similarly had CMV titers measured at selected intervals after transplant and during febrile episodes. Appropriate viral cultures were simultaneously performed. Laboratory evidence of infection was correlated with symptoms and signs of active CMV disease. Mean follow-up period was 20 +/- 12 months with a range of 3-51 months. Three patients were excluded due to early acute rejection resulting in graft loss. Twenty-eight of 41 donors (68%) and 22 of 41 recipients (54%) had positive CMV titers before transplantation. Six of 41 recipients (15%) subsequently developed clinical and laboratory evidence of CMV infection: three of 19 seronegative recipients and three of 22 seropositive recipients. All six patients received kidneys from seropositive donors. Four patients had severe CMV disease (2 seronegative, 2 seropositive), whereas two patients had leukopenia and fever only. Two patients with severe CMV infections subsequently lost their grafts due to unrelated causes. Overall, actual patient and graft survival of the entire group is 95% and 82%, respectively. In conclusion, individuals who receive LRD kidneys from seronegative individuals are unlikely to develop CMV infection, and transplantation of seropositive LRD kidneys may be associated with transmission of CMV in susceptible recipients regardless of their serologic status. With appropriate management of CMV illness in the posttransplant period, LRD kidney donation is safe and efficacious and should not be discouraged on the basis of pretransplant CMV serology in any donor-recipient pairing.     

Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation

Twenty-seven patients received pulmonary transplants during the period since we began routine use of cytomegalovirus-seronegative blood products for CMV-seronegative recipients. Preoperative serologic status of the recipient and the occurrence of cytomegalovirus infection in the postoperative period were correlated with development of obliterative bronchiolitis (OB) as diagnosed by transbronchial biopsy (TBB). Patients included 20 heart-lung and 7 double-lung recipients. OB occurred in 18 of 27 patients. All 3 CMV seronegative recipients receiving lungs from a seropositive donor and 9 of 10 CMV recipients seropositive at the time of transplantation developed OB compared with only 6 of 14 CMV seronegative patients receiving seronegative grafts (P = 0.018). CMV infection occurred in 10/27 patients, of whom 5 were asymptomatic; 90% of these patients developed OB. Donor-specific alloreactivity, based on primed lymphocyte testing (PLT) of bronchoalveolar lavage cells was found at the time of diagnosis of OB in 23 of 27 patients. A positive PLT was significantly associated with the presence of OB (P = 0.017). We conclude that preoperative seropositive status for CMV, grafting of organs from seropositive donors, and postoperative CMV infection are significant risk factors for developing OB. That OB is, in part, an immunologically mediated form of injury and represents chronic rejection is supported by the presence of donor-specific alloreactivity in BAL lymphocytes from all recipients with OB.     

The prevalence of seropositivity for human immunodeficiency virus in patients who have severe trauma.

Patients who have severe trauma have been reported to have a substantially increased rate of seropositivity for human immunodeficiency virus when compared with the general population. We reviewed the records of 1226 consecutive Code-3 trauma patients who were treated at our institution in San Antonio, Texas, between 1987 and 1989. All of the patients had serum drawn to be tested for the human immunodeficiency virus. In contrast with previously published studies, only 0.8 per cent of these trauma patients were seropositive. There was no appreciable difference between the prevalence of seropositivity in patients who sustained blunt trauma and those who sustained penetrating trauma. Exposure to human immunodeficiency virus for medical personnel who care for trauma patients remains a concern, but the risk may be lower than previously reported.     

Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.     

Sustained Epstein-Barr virus detection in paediatric liver transplantation. Insights into the occurrence of late PTLD.

Epstein-Barr virus (EBV) infection is the main cause of post-transplant lymphoproliferative disease (PTLD). Little is known on chronic carrier state and its relation with late PTLD. We aimed to study EBV infection in the long-term after paediatric liver transplantation (OLT). We conducted a retrospective review of 34 children monitored for a median of 5.8 years (range 1.5-17.7). 21 were IgG seronegative (group A) and 13 seropositive (group B) before OLT. Primary infection was the appearance of VCA-IgM or VCA-IgG or Real-Time Polymerase Chain Reaction (RT-PCR) in patients previously IgG seronegative; positive VCA-IgM or EA-IgG or RT-PCR lasting longer than 6 months was defined sustained viral detection (SVD). 18/21 patients of group A had a primary infection at a median time of 3 months after transplant (0.5-60). 14/18 of group A and 0/13 of group B had a SVD (P < 0.0001). Viral loads greater than 500 copies/10(5) mononuclear cells occurred in 12/18 patients in group A and 0/13 patients in group B (P < 0.0001). The 3 patients who developed late PTLD (median time after OLT 47 months, range 15-121) were from group A, and presented with SVD before developing PTLD. In conclusion, EBV infection in seronegative patients at OLT is associated with greater viral loads and sustained viral detection. Late PTLD occurred only in na?ve patients with markers of SVD. Three to 4 monthly long-term monitoring of EBV in pre-OLT na?ve patients might help preventing the occurrence of late PTLD.     

Role of CMV pneumonia in the development of obliterative bronchiolitis in heart-lung and double-lung transplant recipients

Obliterative bronchiolitis (OB) is the main cause of late mortality after lung transplantation. Cytomegalovirus infection has been associated with late graft failure. The aim of this study was to determine whether the development of OB was related to CMV pretransplant serological status and to CMV infections. The study group comprised 36 lung transplant recipients (27 HLT and 9 DLT) who survived more than 4 months, of whom 47% developed OB (defined by the persistence of an unexplained obstructive disease: FEV1/VC < 0,7). OB occurred more frequently: (1) in seronegative recipients with seropositive donors (8/9) than in seropositive recipients (7/19) or seronegative well-matched recipients (2/8); and (2) in patients who experienced CMV pneumonia (11/16) and CMV recurrence (11/16). Since matching seronegative recipients is the best way to prevent CMV infection, we believe that seronegative grafts must be reserved for seronegative recipients.     

Cytomegalovirus infection in seronegative patients treated with prophylaxis: case-controlled study

Primary cytomegalovirus (CMV) infection is common in infancy with approximately 90% to 95% of subjects developing antibodies against this virus. CMV seronegative renal allograft recipients generally receive this infection with a graft or with blood transfusions, showing a high morbidity and mortality. Prophylaxis in these patients has shown good results; however, the published studies have included a small number of patients. Our case-controlled study evaluated 163 kidney transplant recipients: 76 seronegatives for CMV and 87 seropositive for CMV as controls. The evaluated parameters were: CMV infection, CMV disease, renal function, and survival of the patient and graft. We studied our experience among CMV seronegative patients treated with various prophylaxis guidelines. Our conclusions were that CMV prophylaxis in seronegative patients was effective because it showed a risk of infection that was equal (or even less) than that in seropositive patients and revealed a delay in the onset of the disease. CMV seronegativity may be a positive prognostic factor for graft survival.     

Pretransplant recipient cytomegalovirus seropositivity and hemodialysis are associated with decreased renal allograft and patient survival

BACKGROUND: Pretransplant systemic inflammation has been associated with decreased renal allograft survival, and infectious agents such as cytomegalovirus (CMV) may play a role. We hypothesized that pretransplant CMV seropositivity is a risk factor for decreased patient and allograft survival after cadaveric renal transplantation and that other factors believed to modulate systemic inflammation, such as dialysis modality, might act synergistically with CMV to decrease patient and allograft survival. METHODS: The United Network for Organ Sharing database was reviewed to identify all patients undergoing cadaveric renal transplantation in the United States from 1988 to 1997. Outcomes for CMV seropositive and seronegative recipients of organs from CMV seronegative donors were analyzed. Subgroup analysis was performed to identify any synergistic influence on outcome between CMV serostatus and known determinants of risk, including degree of human leukocyte antigen mismatch, pretransplant dialysis, and cold ischemia time. RESULTS: Of 29,875 patients who underwent transplantation, 12,239 were CMV seronegative and 17,636 were CMV seropositive. Patient survival was decreased by pretransplant seropositivity (relative risk [RR] 1.11, P =0.001). In addition, this group demonstrated worse overall allograft survival (RR 1.05, P =0.029), although this adverse effect disappeared when patients who died with a functioning graft were censored. Decreased allograft survival was most pronounced in patients who were on hemodialysis before transplantation (RR 1.62, P =0.004). CONCLUSIONS: Pretransplant CMV seropositivity is associated with decreased patient survival. Pretransplant CMV seropositivity and hemodialysis have a synergistic adverse effect on graft survival, independent of patient mortality. Additional studies are required to define mechanisms by which pretransplant CMV infection and dialysis modality may contribute to decreased allograft survival.     

Should Helicobacter pylori infection be treated before kidney transplantation?

BACKGROUND: Before the introduction of modern medication for ulcer disease, gastroduodenal complications were often fatal in recipients of kidney transplants. Helicobacter pylori causes gastritis and is an important risk factor for peptic ulcer disease and gastric malignancies. The aim of this study was to evaluate whether H. pylori infection influences the outcomes of kidney transplantation. METHODS: Between 1991 and 1994, serum H. pylori antibodies were determined in samples taken just before transplantation from 500 consecutive recipients of kidney transplants. Clinical data were collected retrospectively by means of questionnaires sent to the patients and from the national kidney transplantation registry. RESULTS: The prevalence of seropositivity of H. pylori was 31% in the 500 renal transplant subjects, and the seropositivity increased with age. There were no differences in patient or graft survival between the seronegative and seropositive patients. During the first 3 months after transplantation, five seronegative and one seropositive patient had gastroduodenal ulcers, with bleeding complications in three of the seronegative ones. After 3 months, there were more ulcers in the seropositive group (6 vs 3%) and more oesophagitis in the seronegative group (9 vs 7%). During the 6-year follow-up, two cases of gastroduodenal malignancies were found in the helicobacter-positive group and none in the seronegative group. CONCLUSIONS: Helicobacter pylori infections did not result in significant postoperative gastric complications. Two of the 155 seropositive patients developed gastroduodenal malignancies.     

Mycobacterial infection in patients infected with the human immunodeficiency virus.

Of 207 homosexual or bisexual patients with the acquired immune deficiency syndrome (AIDS), 24 with the AIDS related complex, and 39 with asymptomatic HIV infection, 32 patients were found to have mycobacterial infection. Mycobacterium tuberculosis was found in 13 patients with AIDS and in two with the AIDS related complex. M avium-intracellulare was found in 15 patients with AIDS and was disseminated in 12. One patient was infected with M kansasii and one with M ulcerans. Invasive procedures were frequently required to obtain positive bacteriological results. Subclinical carriage of M avium-intracellulare and other mycobacteria thought to be nonpathogenic was common in patients seronegative for the human immunodeficiency virus and at all stages of human immunodeficiency virus infection. All but one isolate of M tuberculosis were fully sensitive to standard antimycobacterial antibiotics. Response to treatment was usually rapid. M avium-intracellulare isolates were all resistant to first line agents in vitro, and antibiotics such as ansamycin and amikacin were required to obtain a clinical response.     

Human herpes virus 8 infection in kidney transplant patients from an area of northwestern Italy (Piemonte region).

BACKGROUND: Human herpes virus 8 (HHV-8) infection is associated with Kaposi sarcoma (KS) and other neoplastic and non-neoplastic manifestations. A strong association between HHV-8 and KS has been evidenced in transplant recipients, particularly kidney recipients. METHODS: We have investigated the HHV-8 seroprevalence by an immunoenzymatic assay in 408 patients awaiting kidney transplantation and in the corresponding 356 donors; moreover, we have tested for the presence of HHV-8 DNA by nested PCR in available serum samples of the same graft recipients at 6, 12 and >18 months post-transplantation (overall 156 specimens). Associated factors, such as age, sex, area of residence, potential for HHV-8 transmission via organ transplantation and development of KS were also investigated. RESULTS: Twenty (4.9%) of 408 patients and 7 (1.9%) of 356 donors were seropositive. HHV-8 seropositive patients were on average about 6 years older than seronegative individuals. No difference in prevalence by gender was found. Considering the area of residence of seropositive patients, 4/161 (2.48%) were resident in Piemonte vs 16/247 (6.47%) in other areas of Italy (P = n.s.). During the follow-up post-transplantation, HHV-8 DNA was found only in four patients who were seropositive before transplantation, in three cases the corresponding donor was seronegative, in one the corresponding donor was also seropositive and the recipient developed KS. At >18 months post-transplantation, two patients were HHV-8 DNA positive, both were seronegative pre-transplantation and their corresponding donors were seronegative. CONCLUSIONS: HHV-8 seroprevalence in the Piemonte region seems to be low, also in a population of kidney transplant recipients. Based on our data, it does not seem that the immunosuppressive regimen favours the reactivation of HHV-8. Our results do not suggest the possibility of HHV-8 transmission via organ transplantation. Incidence of KS among HHV-8 seropositive patients was very low.     

Protocol for Optimizing the Use of Kidneys From Donors With Seropositivity for Hepatitis C Virus in Seronegative Recipients

BackgroundThe rapid identification of the viral load from hepatitis C virus (HCV) in seropositive donors enables the determination of their infection capacity and the subsequent design of a strategy to optimize the use of direct-action antivirals (DAA) in seronegative recipients. In 2017, we designed an optimization protocol; this study aims to assess its efficacy and safety.MethodsThis is a prospective, multicenter observational study that complies with the Declarations of Helsinki and Istanbul. Donors were HCV seropositive. The HCV and human immunodeficiency virus loads were immediately determined in the donors. For viremic donors, recipients were treated with DAA for 8 weeks. For nonviremic donors, DAA was started if a viral load was detected during the follow-up period. The minimum follow-up period was 6 months posttransplant.ResultsThis study recruited 28 donors. Just over half of the donors (n = 15; 53.5%) had a nonactive history of injection drug use. Eight (22.4%) donors were viremic, and 20 (87.6%) were nonviremic; 13 (65%) had been treated previously. Nine grafts were ineligible for the protocol. We performed a total of 47 transplants. Procedure I (viremic donors) was performed in 13 recipients (27.7%). Posttransplant viremia was observed in 6 participants. Posttransplant viremia was low (<100 IU/mL) in 4 participants but high (36,000 and 138,000 IU/mL) in 2 participants who had initiated DAA after the transplant; all these patients had a sustained viral response. Seroconversion was observed in 11 of 13 (84.6%) patients. Procedure II (nonviremic donors) was undertaken in 34 (82.3%) patients. No positive viral loads were observed. Seroconversion occurred in 7 of 34 (20.5%) recipients. All recipients maintained kidney function at 6 months posttransplant, except 1 patient with a graft that had never been functional and another patient who died of pancreatitis. Both patients had received kidneys from nonviremic donors.ConclusionsOur experience supports the efficacy and safety of this protocol.     

Serological and molecular studies of Epstein-Barr virus infection in allogeneic marrow graft recipients

We have shown in two allogeneic bone marrow transplant recipients that Epstein-Barr virus can be eradicated by the BMT procedure or its complications, and that these patients are susceptible to infection with a new EBV strain. This conclusion was based on a combination of EBV serology and virus strain identification ("Ebnotyping," using the size variations of 5 EBV nuclear antigens). In the present study, we conducted a serological survey of EBV infection in 153 marrow graft recipients and their donors. Ten patients who were positive for IgG antibodies against EBV viral capsid antigens prior to BMT became completely seronegative at a median of 197 days post-BMT (range 106-320 days). Four of these patients, who had received seronegative marrow, remained seronegative during prolonged periods (222 to 2105 days). Six patients had received seropositive marrow. Two of them remained seronegative during their subsequent periods of follow-up (895 and 1437 days). An additional 10 patients showed a 100-fold or greater decrease in VCA IgG antibody titers. Their titers reached a nadir of 10 (the lower limit of positive) at a median of 134 days post BMT (range 83-386 days). The serological patterns of the above 20 patients were particularly frequent among patients with chronic graft-versus-host disease; 12 of 20 patients with decreasing VCA titers (60%) developed chronic GVHD versus only 22 of 73 patients with stable or increasing VCA titers (30%). These results suggest that GVHD may contribute to the elimination of residual EBV-carrying recipient cells. Establishment of EBV-carrying lymphoblastoid cell lines (LCL) was attempted in 60 donor-recipient pairs whose cryopreserved peripheral blood mononuclear cells were available. LCL were established from 18 of 51 EBV-seropositive marrow donors and 10 of 57 seropositive recipients prior to BMT. The same EBV strain was detected in 4 of the 6 cases in which LCL could be established from both the donor and the recipient prior to BMT. The persistence of the original EBV strain was demonstrated in a recipient of a T cell-depleted graft who showed only transient hematological recovery and no GVHD, and was associated with the persistence of B cells of recipient origin.     

Cytomegalovirus infection following renal transplantation in patients administered low-dose rituximab induction therapy

Anti-CD20 antibody (rituximab) is recently being used as a B cell-depleting agent in renal transplantation (RTx). However, the incidence of infectious complications associated with rituximab therapy remains uncertain. We evaluated the incidence of cytomegalovirus (CMV) infection associated with rituximab therapy in RTx. A total of 83 patients were enrolled. The immunosuppressive regimen consisted of tacrolimus or cyclosporin, mycophenolate mofetil, methylprednisolone and basiliximab. In 54 patients, only one dose of rituximab (200 or 500 mg/kg body weight) was given before RTx. A total of 25 of 43 (58.1%) recipients who were CMV seropositive prior to RTx and who received rituximab induction therapy developed CMV infection, compared to 18 of 24 (75%) CMV seropositive recipients who did not receive rituximab therapy ( P  = 0.1676). A total of 8 of 11 patients who were CMV seronegative prior to RTx and who received rituximab developed CMV infection. However, CMV seroconversion was seen in all 8 of these infected patients. Low-dose rituximab induction therapy in renal transplant recipients appears to have no influence on the incidence of CMV infection and CMV seroconversion. However, we have to consider anti-CMV prophylaxis therapy, because of high incidents of CMV infection, especially for CMV seronegative recipients who received rituximab.