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Biomedical subjects

B Gridelli

Publications and source records attributed to B Gridelli.

At least 19 recordsLinked to original sources
PubMed2001

[Strategies for a greater supply of organs for transplantation].

The number of recipients waiting for a solid organ transplantation has increased greatly in the past 5 years. The supply of donor organs during this period has not kept pace, resulting in a large shortage of suitable organs. In an effort to overcome the disparity between supply of donor and demands, various strategies have emerged to expand the existing donor selection criteria. Kidneys from very old donors can be used successfully when a pre-transplant biopsy shows a modest degree of glomerular injury. Kidneys from donors of 50 years or more, or with a history of hypertension and diabetes, or other evidence of renal disease, currently not accepted for single' kidney transplantation, provide excellent function when transplanted together. In contrast, one liver can be enough for two patients. Split-liver transplantation, i.e. sharing one liver between an adult and a pediatric recipient, is becoming routine procedure and has the potential for meeting the need for liver replacement among children without interfering with adult waiting list. Splitting the liver for transplantation in two adults is a further step forward in the more efficient use of hepatic grafts from cadaver donors. Adult-to-adult living donor liver transplantation can further alleviate the pressure in the waiting list, but the risk for the donor must not be underestimated. The decrease in the number of heart-lung transplants in favour of more single and double lung transplants has also made more hearts and more lungs available. It is difficult to quantify the impact of all these procedures on the shortage of organ donors, but the waiting list should be cut by at least one-third for kidney and may be more for liver and lung transplants.

Adult↗
PubMed2001

Anti-CD20 antibody (rituximab) administration in patients with late occurring lymphomas after solid organ transplant.

BACKGROUND AND OBJECTIVES: Aggressive diffuse large cell non-Hodgkin's lymphoma (DLCL) occurring late after a solid organ transplant fails to regress after discontinuation of immunosuppression. Moreover, chemotherapy treatment is associated with a high mortality rate due to severe toxicity. Since the majority of post-transplant lymphoproliferative disorders derive from B-lineage lymphocytes, the administration of anti-B monoclonal antibodies represents a rational therapeutic option. DESIGN AND METHODS: Five patients who developed CD20-positive DLCL more than two years after heart or liver transplantation were treated with a weekly chemotherapy program (2 patients), radiotherapy (2 patients) and surgery (1 patient) followed by a minimum of 4 intravenous doses of rituximab (375 mg/m(2)). RESULTS: A favorable clinical outcome was observed in three patients in whom surgery or radiotherapy had produced significant tumor debulking. Only a partial clinical effect was documented in the two patients with advanced clinical stage disease. INTERPRETATION AND CONCLUSIONS: Rituximab can be safely administered to patients with aggressive CD20-positive DLCL occurring late after a solid organ transplant. However, a positive clinical outcome may be expected only in patients in whom surgery or radiotherapy has achieved significant regression of tumor burden.

Adult↗
PubMed2000

Predictive value of Epstein-Barr virus genome copy number and BZLF1 expression in blood lymphocytes of transplant recipients at risk for lymphoproliferative disease.

Epstein-Barr virus (EBV) genome numbers and RNA transcripts from the immediate-early EBV gene BZLF1 were monitored by means of polymerase chain reaction in peripheral blood lymphocytes (PBLs) of 44 children who received liver transplants. The 2 tests were compared, using several parameters to assess their value as predictors of posttransplantation lymphoproliferative disease (PTLD). All patients were infected with EBV. BZLF1 mRNA was positive in 70% of patients, with highest expression in those with largest virus load. Four patients developed PTLD that could not be unequivocally diagnosed by any of the parameters considered alone. Sensitivity of EBV genome number (>/=40,000 EBV copies/10(5) PBLs) and BZLF1 mRNA (BZLF1:glyceraldehyde-3-phosphate-dehydrogenase ratio >/=0.5) was 100%. Specificity of each of the 2 tests alone (98% and 58%, respectively) improved (to 100% and 83%, respectively) when measurement of serum IgG level was included. Because decreased virus load, but not BZLF1 mRNA expression, accurately predicted favorable responses of PTLD to therapy, monitoring of EBV genome numbers alone appears sufficient in children with liver transplants.

Adolescent↗
PubMed2000

Susceptibility of chacma baboons (Papio ursinus orientalis) to infection by hepatitis B virus.

BACKGROUND: Because baboons are being considered as a source of xenografts for human liver transplantation in patients with hepatitis B virus- (HBV) induced cirrhosis to forestall infection of the graft by the virus, we undertook a study to ascertain if baboons are resistant to HBV infection. METHODS: Six chacma baboons were inoculated with serum containing HBV and were followed for 52 weeks to detect transmission of infection. RESULTS: Anti-HBc was detected in the serum of four baboons 16 weeks after inoculation. Virions, small spherical particles, and tubular forms were seen at this time in the serum of the one baboon studied by transmission electron microscopy. HBV DNA was detected by polymerase chain reaction in the serum of the same four baboons throughout the period of follow-up, as well as in liver tissue obtained after 52 weeks. The specificity of the DNA was confirmed by Southern hybridization. Nucleotide sequences showed complete sequence identity between the HBV DNA in each of the baboon sera and one of the two HBV genotypes inoculated. Serum transaminase levels tested at 4-weekly intervals were always normal and histological examination of liver tissue after 52 weeks showed no evidence of chronic hepatitis. Examination of squash preparations of liver tissue by electron microscopy in one baboon revealed core-like particles. CONCLUSIONS: Chacma baboons are susceptible to HBV infection and appear to develop a chronic carrier state. The use of xenografts from baboons should preferably be avoided, but if they are used again for HBV-infected patients it would be prudent to treat the patients as if they had received an organ from a human donor.

Animals↗
PubMed2000

Epstein-Barr virus-negative lymphoproliferate disorders in long-term survivors after heart, kidney, and liver transplant.

BACKGROUND: Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. METHODS: We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. RESULTS: All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. CONCLUSIONS: Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.

Adolescent↗
PubMed2000

Liberal policy of split liver for pediatric liver transplantation. A single centre experience.

We adopted a liberal policy of extensive use of split liver in a pediatric liver transplantation (LT) program. Over a 19-month period, we have performed 64 LT in 54 patients with pediatric indications. One patient received two liver grafts as a part of a liver-small bowel transplantation and was not considered. Of the 60 LT considered, performed in 53 patients, 34 were with split grafts. The 1-year actuarial survival for the patients transplanted with a split graft was 81% and 89% when only elective cases were considered. The median time on the waiting list was 22 days with no mortality. The extensive use of split liver allowed transplantation in a large number of pediatric patients, with good results without the need for living donor liver transplantation. We envisage a trend towards systematic splitting of liver grafts.

Actuarial Analysis↗
PubMed2000

Rejection and tacrolimus conversion therapy in paediatric liver transplantation.

Rejection and efficacy of rescue therapy with tacrolimus were evaluated in 50 children who underwent primary, ABO-compatible, liver transplantation. Six patients who died within the first week and one child who underwent retransplantation from an ABO-incompatible donor were excluded from the study. No patient or graft were lost due to rejection. We observed 48 episodes of rejection in 33 patients. Fourteen patients required conversion to tacrolimus for steroid-resistant rejection with resolution of rejection. One of these children developed PTLD. Other indications for conversion were neurotoxicity and hirsutism. One patient developed blindness of unknown origin after the conversion. Other side effects of tacrolimus were minor and resolved by lowering the dose. Five patients developed rejection after conversion; all achieved resolution with either steroid therapy or increase of tacrolimus dose. In conclusion, our study confirms that tacrolimus is an effective rescue therapy for paediatric liver transplantation.

ABO Blood-Group System↗
PubMed2000

Circulating Epstein-Barr virus DNA to monitor lymphoproliferative disease following pediatric liver transplantation.

Epstein-Barr virus (EBV) infection can induce uncontrolled lymphocyte B proliferation in immunosuppressed transplant patients. Monitoring circulating EBV-infected lymphocytes can help in identifying patients at risk of posttransplant lymphoproliferative disease (PTLD). Circulating EBV genome levels were determined in 54 liver transplant pediatric recipients. Ten patients had more than 500 EBV genome/10(5) peripheral blood lymphocytes (PBL) and exhibited clinical manifestations of EBV infection; three developed PTLD. To treat EBV infection, the level of immunosuppression was reduced and acute rejection developed in 4 patients. Three were treated with steroid and one had to be switched from cyclosporine to tacrolimus. Treatment of acute rejection was associated with increases in circulating EBV genome. None of the patients with less than 500 EBV genome/10(5) PBL developed PTLD or EBV infection. Monitoring of EBV DNA is useful in the management of EBV infection and PTLD following pediatric liver transplantation. EBV infection should be treated in ways which do not expose patients to the risk of rejection.

Adolescent↗
PubMed2000

Extensive use of split liver for pediatric liver transplantation: a single-center experience.

The results of the extensive use of in situ liver splitting in a pediatric liver transplant program are presented. All referred donors were considered for split liver, and when the donor-recipient body weight ratio (DRWR) was greater than 2, the grafts were split. A modified split-liver technique was adopted when the DRWR was 2 or less. Eighty liver procurements were attempted and 72 (90%) were performed, enabling 65 children to receive 42 split, 22 whole, and 8 reduced-size livers. The right portions of the grafts were transplanted by other centers into adults. Median patient waiting time was 22 days, with no mortality on the waiting list. After a median follow-up of 14 months, overall patient and graft survival rates were 85% and 81%, respectively. Fifty-eight children received a single allograft, whereas 7 children required retransplantation. Two-year actuarial survival rates were 85% for split-liver recipients, 84% for whole-liver recipients, and 67% for reduced-size liver recipients. Vascular complications developed in 18% of the patients, with no difference among the 3 groups with different technique. Biliary complications developed in 25% of the children, mainly in reduced-size and split-liver recipients. Patient and graft survival rates for right split-liver grafts were 84% and 79%, respectively. Adopting a liberal policy of liver splitting provides allografts of optimal quality for pediatric transplantation, allowing a dramatic decrease in the waiting list time. The in situ split-liver technique should be considered the method of choice for expanding the cadaveric liver donor pool.

Adolescent↗
PubMed1999

Immunity to poliomyelitis, diphtheria and tetanus in pediatric patients before and after renal or liver transplantation.

Few studies have considered the safety, efficacy and appropriateness of vaccinations in pediatric patients before and after solid organ transplantation. The aim of this study was to evaluate the immune status after primary vaccination to diphtheria, tetanus and poliomyelitis in pediatric patients before and after hepatic transplantation and to poliomyelitis in pediatric patients before and after renal transplantation. All the patients had received a complete primary immunization schedule for diphtheria and tetanus and poliomyelitis. Immunity to the three polioviruses was evaluated in 56 patients with renal transplant, 27 on chronic dialysis and 33 controls and in 39 patients with hepatic transplant, 25 with chronic hepatic failure and their 36 controls. Immunity to diphtheria and tetanus was evaluated in 52 liver transplant patients, 29 children with chronic hepatic failure and 54 healthy children. Renal transplant patients were less protected and had lower antibody geometric mean titers than healthy controls for polioviruses 1 and 2. Whereas, protection in the children liver transplant patients was similar to that in their controls. Patients with chronic hepatic failure had higher antibody geometric mean titers to diphtheria and polioviruses 1 and 3 than their control group. Immunosuppression after transplantation has a negative influence on the immune status after primary vaccination in children with renal transplant. Whereas children with chronic hepatic failure have higher antibodies than a normal population. When possible, it could be advisable to individualize immunization schedules in patients at high risk.

Adolescent↗
PubMed1998

Post-hepatitis primary disease does not influence 6-year survival after liver transplantation beyond 1 year.

Orthotopic liver transplantation (OLT) is used as a definitive treatment for end-stage liver disease and prolonged posttransplant survival has already been reported. The incidence of late mortality and graft morbidity is, however, not well defined and the role of primary viral disease in the long-term follow-up results is not clear. Data of posttransplant follow-up in 213 patients, 156 adults and 57 children, who survived at least 1 year were reviewed in order to define causes of graft dysfunction, graft loss and death. In 98 patients, 103 persistent graft dysfunctions were found. Thirty-four grafts were later lost [28 deaths and 6 successful retransplantations (re-OLT)]. The results were reviewed grouping patients according to their age and viral hepatitis status at the time of the transplantation. HBV-positive patients (51) showed 4 re-OLT (1 HBV), 3 liver-related deaths (2 HBV), 24 graft dysfunctions (8 HBV, 5 HCV), and 85.2% 6-year survival (based on 100% survival at 1 year). HCV-positive adults (28) showed 1 re-OLT, 3 HCV-related deaths, 24 graft dysfunctions (19 HCV), and 68.8% 6-year survival. HBV-HCV-positive patients (14) showed no graft loss and death, 10 graft dysfunctions (7 HCV, 1 HBV, 2 HBV-HCV), and 81.8% 6-year survival. HBV-HCV-negative adults (63) showed 3 non-hepatitis-related re-OLT, 5 liver-related deaths (2 HCV), 24 graft dysfunctions (6 HCV, 2 HBV), and 83.1% 6-year survival. HBV-HCV-negative children (49) showed no re-OLT, 1 HCV-related death, 14 graft dysfunctions (3 HCV), and 92.6% 6-year survival. HCV-positive children (8) showed 1 HCV-related re-OLT, 2 HCV-related deaths, 4 graft dysfunctions (3 HCV), and 81.3% 6-year survival. The main cause of graft dysfunction was hepatitis (45 HCV and 13 HBV), followed by technical complications (21), rejection (16), recurrent alcoholism (3), HIV infection (1), and unknown causes (4). In this long-term post-transplant follow-up series, viral hepatitis led to graft dysfunction in 58/103 (56.3%) cases, late graft failure was viral hepatitis-related in 11/ 20 (55%) cases, and, as a total, HCV infection was present in 45/58 (77.5%) cases of viral hepatitis-related graft damage. Looking at the timing of hepatitis-related graft failure, in 70% of cases death occurred after the 5th post-transplant year. In our experience, the occurrence of hepatitis, particularly HCV induced, was common and led to abnormal graft function, but the 6-year post-transplant survival (based on 100% survival at 1 year) in patients surviving for at least 1 year did not differ on the basis of the pretransplant viral hepatitis status. This finding may be consistent with the slow progression of the viral damage and longer follow-up results remain to be established. Nevertheless, data from the present study suggest that in long-term liver transplant survivors, the risk of deteriorating liver damage and eventual failure after 5 years remains only in those patients experiencing a viral hepatitis infection.

Adolescent↗
PubMed1998

Rescue FK506 early conversion for refractory rejection after pediatric liver transplantation: experience in 20 children.

Tacrolimus (FK506) is an effective and relatively safe novel immunosuppressant able to revert refractory rejection after pediatric liver transplantation (LTx). Between April 1993 and October 1996, 20 pediatric patients were converted to tacrolimus for biopsy-proven, steroid-resistant liver rejection. The mean follow-up was 18 months. The median time from LTx to switch was 20 days. Tacrolimus was administered per os at a mean dosage of 0.23 mg/kg per day to maintain median blood levels of 10.8 ng/ml at 1 week and 9.2 ng/ml at 1 year from the switch. Of the 20 patients, 15 are alive and they all recovered from rejection without the need of OKT3 after conversion. The major causes of death were: one multiorgan failure, two infections (cytomegalovirus Aspergillus), one bowel perforation, and one posttransplant lymphoproliferative disease. One patient experienced late side effects and was reconverted to cyclosporine when she was already rescued from hepatic allograft rejection. The results confirm that an earlier conversion to tacrolimus should be recommended after pediatric liver transplantation in order to revert hepatic allograft rejection with the best safety profile.

Child, Preschool↗