Serial sodium Amytal interviews in the clinical setting

A prospective final crossmatch with patient serum and donor lymphocytes using the complement-dependent cytotoxicity assay to identify any performed anti-donor antibody is required for kidney transplantation. The presence of pre-existing antibody may lead to hyperacute rejection of the transplanted kidney. Certain anti-donor antibodies have previously been shown to be ineffective in promoting hyperacute rejection, such as IgM autoantibodies and non-specific IgM lymphocytotoxic antibodies. In this report, we present evidence that IgM HLA alloantibody specific to the donor does not lead to hyperacute rejection and produces graft survival results equivalent to transplants with negative pre-transplant final crossmatches. Forty-eight (48) of 402 patients transplanted over and 8 yr period were transplanted across a positive final crossmatch due to IgM antibodies alone. Three patients exhibited IgM autoantibodies and 26 patients demonstrated non-specific IgM antibodies to lymphocytes. In 15 patients, following a detailed serum screening analysis, a significant correlation (r > 0.9, p < 0.001) was observed between HLA Class I antigens and the presence of corresponding IgM alloantibodies. Five of these patients were subsequently transplanted despite a positive final crossmatch that was clearly demonstrated to be the result of IgM alloantibody to donor HLA Class I specificities. All of these patients continue to have graft function. These results suggest that hyperacute rejection is not mediated by any type of IgM antibody to donor lymphocytes and that kidney transplantation when only IgM antibody is present against donor lymphocytes represents a reasonable opportunity for a safe transplant and successful long-term graft survival.     

Probable antibody-mediated failure of two sequential ABO-compatible hepatic allografts in a single recipient

Two sequential ABO-compatible orthotopic liver allografts failed, despite excellent initial posttransplant function, in a patient with preformed donor-specific alloantibodies. There was no evidence of cell-mediated rejection. Retrospective crossmatching of recipient serum, obtained immediately prior to the first transplant, revealed the presence of lymphocytotoxic antibodies directed against donor class I HLA B17, at a titer of greater than 1:32,768. Similarly, lymphocytotoxic antibodies directed against the second donor's class I HLA A2 phenotype were detected on retrospective crossmatching utilizing both the three-wash Amos technique (TWA-CDC), and the anti-human immunoglobulin augmented technique (AHG-CDC), at a titer of greater than 1:32,768. Anti-class I specific alloantibodies were eluted from both failed liver grafts at titers of 1:256. The hepatic necrosis in zones 3 and 2 that were observed on histologic examination, and the profound refractory consumptive thrombocytopenia subsequent to each transplant may have been the result of antibody-mediated rejection by preformed lymphocytotoxic antibodies. Despite the liver's remarkable capacity to withstand antibody-mediated injury, primary humoral rejection following ABO compatible liver transplantation may occur if extremely high titers of performed allospecific lymphocytotoxic antibodies are present.     

Prognostic value of malignant cells in pleural lavage at thoracotomy for bronchial carcinoma

BACKGROUND: It has been reported previously that liver grafts and liver cells seem to be tolerogenic, based on the high frequency of spontaneous tolerance after orthotopic liver transplantation in rodents and on the phenomenon of portal venous tolerance in other models. The purpose of the current study was to characterize in vivo immune responses to allogeneic hepatocytes transplanted into the portal circulation. METHODS: In this functional model of hepatocyte transplantation, "donor" hepatocytes from mice transgenic for human alpha1-antitrypsin (hA1AT) were transplanted by intrasplenic injection into host mice and the secreted hA1AT protein measured in host serum to determine hepatocellular graft survival. Host immune responses were assessed by measurement of donor-specific alloantibodies and delayed-type hypersensitivity responses. In some experiments, liver nonparenchymal cells (NPCs) were co-transplanted with the allogeneic hepatocyte transplant. RESULTS: Allogeneic hepatocyte transplant into immunocompetent hosts resulted in loss of host serum hA1AT by days 7-10 after transplant, whereas syngeneic hosts maintained long-term hepatocellular graft survival as reflected by persistence of serum hA1AT for > 20 weeks. Allogeneic hepatocyte transplantation resulted in the development of donor-specific alloantibody and delayed-type hypersensitivity responses, as well as a "second set" response of accelerated hepatocellular graft rejection after a second transplant. Pretransplantation or co-transplantation of donor-matched liver NPCs at the time of allogeneic hepatocyte transplantation did not prolong hepatocellular allograft survival. CONCLUSIONS: Allogeneic hepatocytes introduced into the portal circulation via intrasplenic injection are immunogenic not tolerogenic and stimulate a weak humoral and strong cell mediated host immune response in vivo. Co-transplantation or pretransplantation of allogeneic liver NPCs did not protect allogeneic hepatocytes from immunologic rejection.     

Ten years of liver transplantation: an evolving understanding of late graft loss

BACKGROUND: We undertook this study to understand the causes of late graft loss and long-term outcome in orthotopic liver transplantation (OLT) recipients. METHODS: Prospectively collected data of 1174 consecutive OLT in 1045 adult patients who received liver grafts between April 1985 and August 1995 were reviewed. The causes of graft loss, pretransplant patient characteristics, and posttransplant events were analyzed in patients who survived at least 1 year after OLT, in an attempt to establish a link between these factors and graft loss. RESULTS: One hundred fifty-nine (17.9%) grafts were lost after the first year. Of these, 132 grafts were lost by death and 27 by retransplantation. Recipients who survived the first year (n=884) had 5- and 10-year survivals of 81.4% and 67.2%, respectively. Death with a functioning graft occurred in 97 (61%) patients. The main causes of late graft loss were recurrent disease (n=48), cardiovascular and cerebral vascular accidents (n=28), infections (n=24), and chronic rejection (n = 15). Pretransplant heart disease and diabetes were found to be significant risk factors for late graft loss due to cardiovascular diseases and cerebral vascular accidents. CONCLUSIONS: Survival of OLT patients who live beyond the first posttransplant year is excellent. Some patient characteristics may be associated with late graft loss. Compared with previous reports, this study shows an increased incidence of late graft loss secondary to recurrent diseases, de novo malignancies, cardiovascular diseases, and cerebral vascular accidents. Chronic rejection seems to be a less frequent cause of late graft loss. The prevention of recurrent disease and better immunosuppression may further improve these results.     

The lack of long-term detrimental effects on liver allografts caused by donor-specific anti-HLA antibodies

Recent reports indicate a higher incidence of both acute and chronic liver allograft rejection when, at the time of transplantation, the recipients serum contains donor-specific anti-HLA antibodies. From 9/89 to 5/91, 133 liver allografts were performed at our institution. Thirteen liver recipients had donor-specific IgG anti-HLA antibodies (complement-fixing) at the time of transplantation. In eleven patients, antibodies reacted to donor class I antigens while in 1 patient the donor-specific antibody had class II reactivity. Twelve patients have been followed for a minimum of 12 months (median 18 months, range 28-12 months). No hyperacute rejection was seen in any of the cases and four patients had acute rejections. Thus far only one of the twelve patients has biopsy evidence suggestive of chronic liver injury. The remaining have normal liver enzymes and bilirubin. Three of these twelve patients died (one from a myocardial infarction and the others from sepsis) accounting for a one-year graft survival of 75%. There was no significant statistical difference in the one-year graft survival in those recipients without donor-specific antibodies (i.e., 80.5%). In eight of the twelve patients, pretransplant preformed antibody level (PRA) was > 50%. In six of the thirteen patients donor-specific antibody was present at dilutions greater than 1:64. As previously reported, the donor-specific antibody disappeared from the serum posttransplant within hours and did not reappear. In vitro studies demonstrated no factor in portal or hepatic artery blood that could inhibit rabbit complement mediated lysis of anti-HLA antibodies. We conclude that it is not a contraindication to do liver transplants in the presence of donor-specific anti-HLA antibodies.     

Frequency of dissociative disorders among psychiatric inpatients in a Turkish University Clinic

BACKGROUND: Intravenous gammaglobulin (i.v.IG) contains anti-idiotypic antibodies that are potent inhibitors of HLA-specific alloantibodies in vitro and in vivo. In addition, highly HLA-allosensitized patients awaiting transplantation can have HLA alloantibody levels reduced dramatically by i.v.IG infusions, and subsequent transplantation can be accomplished successfully with a crossmatch-negative, histoincompatible organ. METHODS: In this study, we investigated the possible use of i.v.IG to reduce donor-specific anti-HLA alloantibodies arising after transplantation and its efficacy in treating antibody-mediated allograft rejection (AR) episodes. We present data on 10 patients with severe allograft rejection, four of whom developed AR episodes associated with high levels of donor-specific anti-HLA alloantibodies. RESULTS: Most patients showed rapid improvements in AR episodes, with resolution noted within 2-5 days after i.v.IG infusions in all patients. i.v.IG treatment also rapidly reduced donor-specific anti-HLA alloantibody levels after i.v.IG infusion. All AR episodes were reversed. Freedom from recurrent rejection episodes was seen in 9 of 10 patients, some with up to 5 years of follow-up. Results of protein G column fractionation studies from two patients suggest that the potential mechanism by which i.v.IG induces in vivo suppression is a sequence of events leading from initial inhibition due to passive transfer of IgG to eventual active induction of an IgM or IgG blocking antibody in the recipient. CONCLUSION: I.v.IG appears to be an effective therapy to control posttransplant AR episodes in heart and kidney transplant recipients, including patients who have had no success with conventional therapies. Vascular rejection episodes associated with development of donor-specific cytotoxic antibodies appears to be particularly responsive to i.v.IG therapy.     

Effects of aerosolized surfactant in patients with stable chronic bronchitis: a prospective randomized controlled trial

BACKGROUND/AIMS: Fulminant hepatic failure (FHF) is usually fatal without liver transplantation. Auxiliary heterotopic partial liver transplantation (AHPLT) may offer advantages over orthotopic liver transplantation (OLT) or any other heterotopic procedure for the treatment of patients with fulminant liver failure. We studied AHPLT in a severe acute hepatic failure model in pigs. METHODOLOGY: Group A (control: n = 5) underwent portal vein and hepatic artery ligation and side-to-side portocaval shunting. Group B (AHPLT: n = 15) underwent host portal vein and hepatic artery ligation and AHPLT. RESULTS: All of the pigs in group A died within 48 hours from massive liver necrosis. Ten of the 15 pigs (67%) in group B had well-functioning grafts. Five of these ten died between 8 and 17 days postoperatively due to various complications. The remaining five survived for sixty days postoperatively in healthy condition. At the time of sacrifice, four of these five had well-functioning grafts weighing 739 +/- 52 g (mean +/- SEM) and regenerated, but still atrophied, host livers weighing 262 +/- 23 g (p < 0.0002). On the other hand, the one remaining pig had an atrophied graft weighing 310 g and a well-regenerated host liver weighing 470 g, probably due to a late, poorly functioning graft associated with severe rejection. CONCLUSION: AHPLT may result in survival despite host hepatic failure, and the host liver may recover within two months, despite total interruption of blood inflow.     

The contribution of terminal complement components to acute and hyperacute allograft rejection in the rat

Acute rejection and antibody-mediated hyperacute allograft rejection are affected by activation of the complement cascade. Split products of early complement components influence the localization, activation, and effector functions of platelets, granulocytes, monocytes, and lymphocytes, while the formation of membrane attack complex (C5b-C9) can lead to rapid cell destruction. Therefore, we compared acute and Ab-mediated hyperacute allograft rejection in a recently described model of C6 deficient PVG (C-) (RT1c) rats and their normal counterpart PVG (C+) (RT1c) rats. Cardiac allografts from fully MHC disparate ACI donors were heterotopically grafted into naive and skin graft sensitized PVG (C-) and PVG (C+) rats. ACI cardiac allografts were rejected acutely (8.3 +/- 2 days; n = 7) by naive PVG (C+) recipients, but survived significantly longer in PVG (C-) recipients (22 +/- 10 days; n = 10). Presensitized PVG (C+) rats rejected ACI cardiac allografts hyperacutely in 6.1 +/- 2.4 hr (n = 5). In contrast, ACI cardiac allografts transplanted into presensitized (PVG (C-) rats had markedly longer survival of 91 +/- 14 hr (n = 5). The alloantibody responses of naive PVG (C+) and PVG (C-) recipients 7 days after cardiac allografting, and of presensitized PVG (C+) and PVG (C-) recipients at time of cardiac allografting were not significantly different as measured by flow cytometry against ACI lymphocytes. Immunofluorescence demonstrated deposition of IgM, IgG and C3 in ACI allografts in PVG (C-) as well as in PVG (C+) recipients. Deposition of C6 was only found in grafts rejected by PVG (C+). The significantly longer survival of ACI cardiac allografts in C6-deficient PVG (C-) rats indicates that the membrane attack complex contributes to acute as well as antibody-mediated hyperacute allograft rejection.     

Steroid withdrawal from long-term immunosuppression in liver allograft recipients

Corticosteroids were withdrawn from the immunosuppressive regimen of 168/197 (85%) of liver transplant patients who survived for more than three months. In 14, steroids were restarted for reasons other than rejection. The remaining 154 patients were evaluated for the occurrence of rejection and graft loss. Risk factors for the development of rejection after steroid withdrawal were assessed. There were 13 episodes of rejection in 12 (7.8%) grafts; 7 (4.5%) experienced acute cellular rejection, and 6 (3.9%) developed chronic ductopenic rejection. All cases of acute rejection resolved with high-dose steroids. Graft and patient loss due to chronic rejection was 3 (1.9%) and 2 (1.3%), respectively. Chronic rejection resolved in 1 patient, 1 was successfully retransplanted, and in the other 2 the principal cause of death was recurrent tumor. None of the risk factors examined (primary indication for transplant, severity of previous acute rejection, use of OKT3, retransplantation, ABO blood group donor/recipient match, CMV infection, and CsA mono versus CsA and AZA double therapy) were associated with the development of chronic rejection poststeroid withdrawal. The prevalence of side effects, after steroid withdrawal, was low; 66% of patients never required antihypertensive medication; 14% experienced a significant septic episode, and only 4 died with sepsis as the major factor. There were no fungal sepsis and no new cases of diabetes. Withdrawal of corticosteroids after 3 months can be successfully achieved in the majority of liver allograft recipients and is associated with a low rate of rejection, graft loss, and complications attributable to immunosuppressive medication.     

Liver transplantation using grafts from donors over 65

OBJECTIVE: Donors age 50 years was an exclusion criteria in past decades. The increase of patients in the waiting list has determined the acceptance of older donors (over 65 years old). We analyze our results in liver transplantation using donors over 65 years. PATIENTS: From 1986 to may 1994, we performed 381 OLT. In five cases (1.3%) the OLT was performed using donors over 65 years of age (66, 67, 68, 70 and 71). The selection criteria for donors and recipients were similar to the other transplanted patients. Immunosuppression included cyclosporine or FK-506, prednisone and azathioprine. RESULTS: There were no primary graft failures and preservation damage, biochemical and clinical evolution were not different to the procedures using younger donors. Three grafts presented non-corticoresistant acute rejection. After a follow-up of 11.6 mo (range 4-37 mo) only one graft was lost (Kaposi's sarcoma in the liver). Four grafts and four patients are in excellent biochemical and clinical condition. CONCLUSIONS: Donor age should not be an exclusion criteria. Grafts from older donors (over 65 years old) may be considered safe and will permit to increase the number of OLT.     

The neuropathology of orthotopic liver transplantation: an autopsy series of 16 patients

OBJECTIVE: To examine the neuropathologic findings seen in the setting of orthotopic liver transplantation (OLT) and to asses the role, if any, that the neuropathology had in the patient's death. DESIGN: Retrospective autopsy series of 16 patients. SETTING: Tertiary referral center with a high volume of liver transplantation. PATIENTS: Sixteen OLT patients who died and in whom a complete autopsy, including examination of the brain and spinal cord, was performed. RESULTS: Sixteen patients, including 13 women and 3 men, comprised the study group. Patients ranged in age from 25 to 64 years (mean 44.8 years). Postoperative OLT survival ranged from 1 to 1962 days (mean 236 days). Reasons for the initial OLT included hepatitis (n = 6), fulminant hepatic failure (n = 4), cryptogenic cirrhosis (n = 2), methotrexate toxicity (n = 1), postoperative complication (n = 1), primary biliary cirrhosis (n = 1), and hepatocellular carcinoma (n = 1). Autopsies in 13 (81%) patients showed neuropathology; in only 2 patients, however, was the primary cause of death attributable to these findings. The most common neuropathology was related to anoxia or infarction, specifically, ischemia or focal neuronal necrosis (n = 9), infarction (n = 4), and diffuse anoxic encephalopathy (n = 3). Other central nervous system findings included infection with Aspergillus, Candida, and Toxoplasma (n = 3). The most common cause of death was infection-related in 8 patients. One patient died of pulmonary hypertension, 1 of acute rejection, and 1 of possible hyperacute rejection. Two patients died directly as a consequence of neuropathology findings; one had massive central edema with herniation, and the other had a large intracerebral hemorrhage with herniation. The exact cause of death was unclear in 3 patients. CONCLUSIONS: The most common neuropathology findings in this series were related to ischemia and infarction. Neuropathology findings are a significant cause of morbidity, but were only rarely the main cause of death (n = 2) in the OLT patients in this study.     

CsA levels in the early posttransplant period--predictive of chronic rejection in liver transplantation?

The increasing success of clinical liver transplantation has brought rejection to the forefront as a cause of morbidity and graft loss. The relationship of immunosuppressive drug doses and levels to acute and chronic rejection remains a matter of debate. The effect of blood CsA levels and drug doses on the incidence of acute and chronic rejection and the impact of acute rejection episodes on the occurrence of chronic rejection were studied in 146 grafts in 132 patients. These patients were transplanted in the 4-year period from June 1989 using CsA-based immunosuppression (CsA, azathioprine, prednisolone). Liver grafts in patients maintained on median CsA levels (whole blood, trough level) of > or = 175 micrograms/L in the first 28 days posttransplant had a significantly lower incidence of chronic rejection (2 out of 49 vs. 22 out of 97; P = 0.002). There was no significant difference in incidence of graft loss due to fatal sepsis (6% vs. 5%) or nephrotoxicity between the high and low CsA level groups. The overall graft loss rate was lower in the higher CsA level group (22% vs. 37%). The total doses of the individual drugs did not correlate with the incidence of acute or chronic rejection. Although the occurrence of acute rejection itself did not determine later chronic rejection, late occurrence (P < 0.00001) and multiple episodes (two or more; P = 0.0002) of acute rejection were significant risk factors for the occurrence of chronic rejection. We conclude that to minimize graft loss to rejection, CsA levels should be maintained at greater than 175 micrograms/L in the early posttransplant period, and late and recurrent episodes of acute rejection should be prevented.     

Circulating ICAM-1, E-selectin, IL-2 receptor, and HLA class I in human small bowel, liver, and small bowel-plus-liver transplant recipients

Recently, soluble(s) circulating isoforms of intercellular adhesion molecule-1 (sICAM-1) and sE-selectin (formerly endothelial leukocyte adhesion molecule-1) have been described in normal human serum. Elevated levels have been reported in acute and chronic inflammatory disorders, including allograft rejection. In this study, plasma levels of sICAM-1 and sE-selectin were determined in groups of tacrolimus (FK 506)-treated adult patients following either isolated small bowel (SB), liver, or combined SB plus liver (SB/L) transplantation. Each molecule was measured at 1, 2, 4, 6, 8, and 12 weeks (all patients) and at 6, 9, and 12 months after transplantation (SB and SB/L only) by enzyme linked immunosorbent assay. Levels were compared with those of soluble interleukin-2 receptor (sIL-2R; a marker of lymphocyte activation) and soluble HLA class I (which has been reported to be elevated in liver transplant-related complications). Elevations above normal in mean plasma levels of sICAM-1 (2.4-fold), sE-selectin (1.8-fold), sIL-2R (10.6-fold), and sHLA class I (1.3-fold) were found in patients with stable isolated SB grafts during the first 12 weeks posttransplant. Except for sHLA class I, levels of each protein were subsequently reduced, up to 1 year posttransplant. However, further increases in sICAM-1 and in sIL-2R and sE-selectin levels were observed during episodes of SB rejection compared with stable grafts. Mean levels of all molecules were higher in patients with isolated SB grafts compared with those given liver or combined (SB/L) transplants, either during stable SB graft function (up to 12 weeks posttransplant) or rejection. The data demonstrate increased adhesion molecule production/shedding following SB transplantation and are suggestive of a reduced overall level of immune activation in liver and SB/L compared with isolated SB transplantation.     

Identification of regulatory elements of human alpha 6 integrin subunit gene

BACKGROUND: A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. METHODS: Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. RESULTS: Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus < or = 90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted > 90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. CONCLUSIONS: Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.     

Induction of allograft nonresponsiveness after intrathymic inoculation with donor class I allopeptides. I. Correlation of graft survival with antidonor IgG antibody subclasses

We have recently demonstrated that cardiac allograft rejection in the PVG.R8-to-PVG.1U rat strain combination involves the recognition of a isolated class I (RT1.Aa) molecules as peptides in the context of the recipient MHC molecules. Three synthetic peptides (P1, P2, and P3) corresponding to the alpha-helices of the RT1.Aa molecule served as T-cell epitopes for graft rejection. In this study, we demonstrate that two of these peptides (P2 and P3) are sufficient to induce immune nonresponsiveness (median survival time >237 days) to cardiac allografts when presented to the recipient immune system in the thymus 7 days before transplantation. This effect was time dependent, as intrathymic inoculation 60 days before transplantation did not prolong graft survival (median survival time=12 days). Previous studies have demonstrated a critical role for alloantibody responses in mediating graft rejection in this rat strain combination. We, therefore, studied the role alloantibody responses may play in the observed immune nonresponsiveness. The titers of alloantibody in serum samples harvested from graft recipients at different times after transplantation were measured. We used recipient primary aortic endothelial cells genetically manipulated to express the donor RT1.Aa molecule as targets in an enzyme-linked immunosorbent assay. High titers of anti-RT1.Aa IgM antibody were detected in unmanipulated controls at the time of graft rejection. The IgM antibody switched to high IgG titers in intrathymically inoculated rats with accelerated or delayed rejection. Graft rejection in intrathymically manipulated recipients that had achieved a transient state of immunological nonresponsiveness correlated with higher titers of the IgG2b alloantibody. In marked contrast, the long-term graft survivors expressed undetectable or low levels of the IgG2b antibody and moderate to high levels of the IgG1 and IgG2a subclasses. These data suggest that the IgG2b alloantibody may contribute to the rejection reaction, whereas IgG1 and IgG2a may be involved in active enhancement of graft survival.     

Epstein-Barr virus serology and Epstein-Barr virus-associated lymphoproliferative disorders in pediatric liver transplant recipients

Epstein-Barr virus serology was performed before and after transplantation in 116 patients of a total series of 261 pediatric OLT recipients. Thirty-nine percent had no immunity before OLT, but this percentage decreased to 11.2% at 6 months and 10.5% at 2 years after transplantation. In this series, 10 children developed a B cell lymphoproliferative disease. Four had adenotonsillar involvement, 2 of them with associated digestive tract invasion. Three of these are alive, 2 after retransplantation for chronic rejection subsequent to arrest of immunosuppression. The fourth died from bone marrow aplasia. Three patients with multiorgan involvement died from multisystemic failure. The remaining 3 patients had a pseudotumoral mass. Two of these are alive, 1 after retransplantation for hepatic localization and secondary vascular and biliary complication. The last died from cachexia. Four patients developed the syndrome after viral reactivation, and 6 after primo infection. Four patients were under FK506 rescue therapy. We conclude that a high rate of EBV primo infection is observed in the first months after transplantation. A significant percentage will develop EBV-associated lymphoproliferative disease, which causes death in half of the patients, including all these with multiorgan involvement. Half of the patients may survive, but because immunosuppression must be stopped, retransplantation for chronic rejection is often necessary in survivors.     

Acute rejection of marrow grafts in patients transplanted from a partially mismatched related donor: clinical and immunologic characteristics

Bone marrow transplantation (BMT) from a partially mismatched related donor (PMRD) provides a treatment option for patients lacking a matched sibling donor. T lymphocyte depletion of the graft reduces the risk of severe graft-versus-host disease, but may increase the risk of graft failure. We evaluated the pattern of acute graft rejection in eight patients receiving PMRD BMT with respect to the conditioning therapy, diagnosis, age and sex of donor and recipient, degree of HLA mismatch, and peripheral blood immunophenotype at the time of graft failure. All grafts were partially depleted of T lymphocytes. Marrow grafts infused into patients who experienced acute rejection did not differ significantly in nucleated cell dose, degree of T lymphocyte depletion, T cell dose, or CFU-GM/kg infused, from those received by 31 patients who showed durable engraftment. In three of four patients who rejected their grafts, and had sufficient peripheral blood cells for immunophenotyping, a CD3+CD8+ T lymphocyte phenotype was predominant at the time of acute rejection. In one patient rejection was associated with a predominant population of CD3+CD4+ T lymphocytes. Rejection was significantly associated with chronic myelogeneous leukemia and in patients mismatched by more than two antigens.     

Quid? Bilateral renal angiomyolipoma (AML) revealing Bourneville''s tuberous sclerosis (BTS)

The clinical significance of anti-B-cell antibodies in kidney and pancreas transplantation remains unresolved. Here, we report an isolated hyperacute rejection of the kidney, but not the pancreas, during a simultaneous kidney-pancreas (SKP) transplant. The hyperacute rejection was due to IgG antibodies directed against class II antigens expressed on B-cells. Antibodies directed against class II antigens are generally not thought to produce hyperacute rejection, since class II antigens allegedly are minimally expressed on vascular endothelium in the kidney. The pancreas was spared and continues to function normally, suggesting that class II antigens were not strongly expressed in this pancreas. The differential susceptibility to B-cell antibodies of the two transplanted organs is noteworthy and should call attention to the danger from IgG antibodies to class II antigens in kidney transplantation.