Epstein-Barr virus-related localized hepatic lymphoproliferative disorders after liver transplantation

BACKGROUND: Localized hepatic post-transplant lymphoproliferative disease is uncommon. In such cases, lymphocyte Epstein-Barr virus (EBV) infection may promote an intrahepatic B-lymphocyte monoclonal expansion. METHODS: From 1990 to 1991, 149 patients underwent liver transplantation for various liver failures. Immunosuppressive therapy was azathioprine, cyclosporine-A, and methylprednisolone. Rejection episodes were treated by methylprednisolone bolus injection with or without OKT3 therapy. Three patients (2%), aged 38, 50, and 47 years, developed lymphoproliferative disease localized in the transplanted livers within 5 months of liver transplantation (a patient had been immunosuppressed for 3 years before the lymphoproliferative disease occurred within the third allografted liver). Diagnoses were obtained by fine needle aspiration. In situ hybridizations were performed with the kappa/lambda mRNA-kit FITC DAKO (DAKO Corporation, Carpenteria, CA) and the early mRNA-EBER oligonucleotide FITC DAKO: RESULTS: Lymphoproliferative diseases were all classified as diffuse polymorphic large cell lymphomas in the working formulation and considered as lymphoproliferative disorders with polymorphic large cells in the Frizzera classification. All large cells were CD20-positive, CD45-positive and CD45RO-negative. In situ mRNA light chain hybridization demonstrated monoclonality in two cases. In all three cases, EBV mRNA was detected in large cells by early mRNA-EBV (EBER) in situ hybridization. Patients were treated with doxorubicin, cyclophosphamide, vincristine, and VM26. Two patients maintained a complete remission 3 years after six cycles of chemotherapy, whereas one died of an early opportunistic infection. CONCLUSION: Epstein-Barr virus may play a special role in the pathogenesis of lymphoproliferative disorders that develop in patients who have undergone liver transplantation.     

Multiple myeloma after cardiac transplantation: an unusual form of posttransplant lymphoproliferative disorder

Published reports of posttransplant myeloma are extremely uncommon (three cases); to the best of our knowledge there have been no reported cases in cardiac transplant recipients. We are also unaware of any report of Epstein-Barr virus (EBV) genome studies in posttransplant myeloma. We report here the case of a 48-year-old man who developed multiple myeloma 1.5 years after cardiac transplantation. The results of a serum analysis were consistent with past EBV infection. Biopsy of a skull lesion showed a monomorphous population of malignant immature plasma cells that showed monotypic cytoplasmic staining with antibodies to lambda light chains. A monoclonal immunoglobulin heavy chain gene rearrangement was detected by polymerase chain reaction (PCR). Both EBER-1 in situ hybridization and EBNA-1 PCR were negative for the EBV genome. Cyclosporin withdrawal was followed by transient clinical and biological improvement, but the tumor later progressed and eventually stabilized in response to treatment with dexamethasone alone. This case illustrates that posttransplant lymphoproliferative disorders (PTLPDs) encompass not only EBV-positive but also EBV-negative cases and not only lymphomas but also myelomas.     

Allogeneic stem cell transplantation for advanced low-grade lymphoproliferative disorders: report of six cases

BACKGROUND: Allogeneic stem cell transplantation is being increasingly used to treat young patients with poor-prognosis low-grade lymphoproliferative disorders. We report our single-center experience. PATIENTS AND METHODS: Six adults (four with advanced chronic lymphocytic leukemia, one follicular center cell lymphoma and one mantle cell lymphoma) underwent allogeneic stem cell transplantation (SCT). Five received bone marrow while one received peripheral blood stem cells. Donors were HLA-identical siblings in five cases and an HLA-haploidentical sibling in one. The conditioning regimen included in five cases cyclophosphamide, TB1 and high-dose chlorambucil, without the latter in the patient with follicular lymphoma. RESULTS: Five patients successfully engrafted, while the patient who received the haploidentical marrow suffered primary graft failure. There were two cases of grade 2 acute GVHD and one limited chronic GVHD. Four patients are alive in complete remission (CR) with a follow-up of 17+ to 118+ months. Additionally, there is no evidence of residual disease by immunologic and molecular techniques in three cases, while one patient has residual disease assessed by molecular methods. CONCLUSIONS: These results suggest that allogeneic SCT can achieve prolonged remissions in advanced chronic lymphoproliferative disorders.     

Biopsy-induced tricuspid regurgitation after cardiac transplantation

Transvenous endomyocardial biopsy is now well-established as the gold standard for evaluation of possible rejection episodes after cardiac transplantation. From 1985 to August 1992, 1990 patients have undergone 193 cardiac transplantations at Barnes Hospital. One hundred eighty-three patients survived their initial hospitalization and serve as the study group. Their records were reviewed for the purposes of identifying those with tricuspid regurgitation as a complication of right ventricular endomyocardial biopsy. These patients have undergone a total of 2,960 biopsies for an average of 16.2 biopsies per patient. Over a mean follow-up period of 4.22 years, all patients have been evaluated with standard two-dimensional echocardiograms. Mild to moderate tricuspid regurgitation was very common, but was thought to be biopsy-induced only if severe and accompanied by flail components of the tricuspid valve. Twelve patients were identified with this entity at our institution. Of these, 5 had no symptoms and were receiving no diuretics, 3 had mild symptoms consisting of lower extremity edema and continued to receive diuretics, 2 had moderate symptoms, and 2 had right heart failure and anasarca refractory to medical therapy. Both of the severely affected patients subsequently required tricuspid valve replacement. We conclude that the tricuspid valve apparatus is at significant risk of injury during endomyocardial biopsy, that most patients will be minimally symptomatic due to tricuspid regurgitation when this injury occurs, and that when the injury is accompanied by severe symptoms, the likelihood of improvement with medical therapy is small.     

Impaired T cell functions preceding lymphoproliferative disorders in mice neonatally tolerized to transplantation antigens

In A/J (H-2a) (A) mice, the neonatal i.v. injection of (B10 x A)F1 spleen cells (SC) induces partial transplantation tolerance (TT) to C57BL/10ScSn (H-2b) (B10) skin allografts, chronic host-versus-graft disease (HVGD) and lethal lymphoproliferative disorders (LPD). They produce anti-T-cell autoantibodies (ATA), and the proliferative responses of their SC to the T cell mitogen Con A are decreased. We found that, similar to ATA, the hyporeactivity of T cells developed earlier (at 1-2 weeks of age) than splenomegaly. The proportions of both CD4+ and CD8+ T cells were not reduced in the spleens of tolerized mice without manifest LPD. The supernatants (SN) of Con A-stimulated tolerized SC contained no, or only small amounts of interleukin-2 (IL-2). Thus, in the tolerized mice, ATA and T cell deficiency preceded the development of LPD. ATA and the decreased amount of the T cell growth factor IL-2 might play a role in the defective T cell activation.     

Coronary artery fistula after cardiac transplantation

A cardiac transplant recipient with multiple coronary artery fistulae draining into the right ventricle is described. These fistulae presumably resulted from repeated endomyocardial biopsies. The diagnosis of coronary artery fistulae was made at the annual coronary arteriography. The magnitude of the shunt remained small over eight years of follow-up.     

Clinicopathologic features of posttransplant lymphoproliferative disorders

Posttransplant lymphoproliferative disorders (PTLD) are primarily B lymphocyte tumors which are related to the Epstein-Barr virus. Recent studies have more clearly delineated neoplastic from hyperplastic forms of this disease. Factors associated with increased PTLD risk include recipient EBV seronegative status and heavy immunosuppression. The clinical presentation of PTLD is reviewed and lesser known features such as respiratory compromise or localization of tumors to skin are highlighted. The pathologic classifications of PTLD are surveyed and related to one another. Newer approaches to therapy, including the use of monoclonal antibodies and adoptive cellular immunotherapy are discussed.     

Primary lymphoproliferative disorders of the breast

Primary breast lymphoproliferative disorders are rare lesions and include both the malignant lymphomas and the benign pseudolymphomas. We reviewed 4,491 consecutive cases of breast cancer diagnosed and treated between 1973 and 1988. Patients with lymphoma in other sites and those with lymphomas limited to axillary nodes were excluded. RESULTS. Five patients (0.11%) presented with primary lymphoreticular lesions, of which three were primary non-Hodgkin's lymphoma and two were pseudolymphomas. Patients were followed clinically through to the present time or until death occurred. Surgical procedures included incisional or excisional biopsy in four patients and modified radical mastectomy in one. Two patients received chemo-therapy and one received radiotherapy. One patient with pseudolymphoma subsequently developed infiltrating ductal carcinoma of the same breast. Three patients with primary breast non-Hodgkin's lymphoma died within the follow-up period, with a mean survival of 33 months. CONCLUSIONS. We conclude that primary breast lymphoma is a rare and aggressive breast malignancy with a poor prognosis despite different treatment options.     

Malignant lymphoproliferative disorders in liver cirrhosis

BACKGROUND: Lymphoproliferative disorders in patients with liver cirrhosis, although uncommon, have been reported in at least 49 cases. Some authors have suggested that the association between chronic liver disease and lymphoma is not coincidental, that immune mechanisms may be pathogenetically involved. PATIENTS AND METHODS: In the present study we calculated the incidence rate of lymphoproliferative disorders in 334 liver cirrhosis patients (201 males, mean age 59 +/- 12; 133 females, mean age 61 +/- 11) treated at the Gastroenterology Department of the Mauriziano Hospital in Turin from January 1987 to September 1990. RESULTS: We diagnosed 12 lymphoproliferative disorders, corresponding to an incidence of 9.56/1,000 person-years, a figure much higher than expected on the basis of the incidence rate registered in the Turin general population. Six of the 12 lymphoproliferative disorders were non-Hodgkin's lymphomas of the stomach, a proportion by far exceeding expectation. CONCLUSIONS: Our data support the hypothesis that the association between chronic liver disease and lymphoproliferative disorders is not just coincidental, and suggest that liver cirrhosis might be considered an immunological disturbance which entails an increased risk of developing lymphoproliferative disorders. Mechanisms causing lymphoproliferative disorders to develop in the course of chronic liver disease have been hypothesized.     

Reversible graft dysfunction after cardiac transplantation]

Catalase (CAT) activity in ground beef and pork was determined on samples cooked from 60 to 71.1 degrees C. One-gram samples of ground round (4% fat), hamburger (24% fat), and commercial pork sausage (38%fat) were cooked in a controlled-temperature waterbath at 65, 68.3 and 71 degrees C. Chilled samples were immersed in direct contact with the cooking water; the test samples were removed every 15 s and immediately immersed in an ice-water bath (O to 1 degrees C) to quick-chill the samples to prevent temperature over-run. Samples retained high (HMB value 20+, over range) CAT activity through 90, 60, and 45 s at 65, 68.3, and 71 degrees C, respectively, before showing rapid activity decreases. Four USDA-FSIS approved meat patty heating processes (66.1 degrees C, 41 s; 67.2 degrees C, 26 s; 68.3 degrees C, 16 s; and 69.4 degrees C, 10 s) were analyzed for CAT activity in meat frozen prior to cooking was slightly lower (P < 0.05) than in degrees C meat. CAT activity decreased (P < 0.05) among meat treated at 66.1 degrees C for 41 s, at 67.2 degrees C for 26 s, and at 68.3 degrees C for 16 s, but the treatment at 68.3 degrees C for 16 s was not different (P < 0.05) from that at 69.4 degrees C for 10 s. These results show this rapid (20 to 25 min) CAT activity test could be used to establish activity values at specific end-point temperatures for model heat-processed ground beef or sausage products and may be useful to USDA FSIS process inspectors and food processors in quality assurance and HACCP (hazard analysis critical control points) programs for thermal input verification.     

The molecular genetics of post-transplantation lymphoproliferative disorders

The post-transplantation lymphoproliferative disorders represent a significant clinical and diagnostic problem. However, these disorders also represent an important biological model for studying the development and progression of lymphoid neoplasia in immune deficiency. Accurate diagnosis and classification of these disorders requires correlative multiparametric analysis of the clinical behavior of the patient with the histopathological features, immunophenotype, clonal composition, and genetic alterations of the lymphoproliferative disorder. Such analyses should also assist in furthering our understanding of the pathogenesis of these disorders.     

Non-Hodgkin lymphoma of brain occurring after cardiac transplantation

This case report concerns a case of NHL which affected a 56 year-old patient after cardiac transplantation. The patient was hospitalized because of worsening congestive failure. Despite maximal medical treatment the patient continued to be in NYHA Class III-IV and underwent orthotopic cardiac allograft transplantation. The NHL developed in the CNS eighteen months after surgery and had a very quick lethal progression.     

Lymphoproliferative disorders after lung transplantation: imaging features

The intensity of the fluorescence emission of the fluorescent 1,4-dihydropyridine (DHP) derivative felodipine increased upon binding to both isolated cardiac sarcolemma (SLM) and skeletal muscle sarcoplasmic reticulum (SR) preparations, the latter containing SR-transversal tubule junctional diads and triads. The fluorescence enhancement was due to the binding of felodipine to high-affinity (Kd's of 0.35 and 1.25 nM in cardiac SLM and skeletal SR, respectively) 1,4-dihydropyridine sites of the dihydropyridine receptor (DHPR), as evidenced in competition experiments with the DHP analog isradipine. In both cardiac SLM and SR, the felodipine fluorescence was sensitive to conformational changes of the DHPR, as diltiazem that binds to DHPR at a separate site altered the values of both the Kd and the Hill coefficient characteristic for felodipine binding. In skeletal muscle membranes containing intact TT-SR junctions, ryanodine, a specific ligand of the ryanodine receptor calcium release channel (RyRC), also induced changes in felodipine fluorescence, which was eliminated by detergent and high-salt treatment to solubilize the RyRC. These results suggest that i) felodipine fluorescence is useful to probe conformational changes of the DHPR and ii) coupled conformational changes between the DHPR and the RyRC in skeletal muscle indeed occur and could be monitored by measuring felodipine fluorescence.     

Magnesium deficiency and bone loss after cardiac transplantation

Magnesium depletion adversely affects many phases of skeletal metabolism and has been implicated as a risk factor in several forms of osteoporosis. Magnesium deficiency has also been reported after cardiac transplantation. To evaluate whether altered magnesium homeostasis could be related to the pathogenesis of early bone loss after cardiac transplantation, we prospectively measured serum and urinary magnesium and evaluated them with respect to biochemical indices of mineral metabolism and rates of bone loss. The study population included 60 patients (45 men, 15 women) aged 53 +/- 11 years (SD) with measurements of biochemistries and bone mineral density by dual-energy X-ray absorptiometry before and 3 months after transplantation. All received prednisone, cyclosporine A, and azathioprine, plus calcium (1000 mg) and vitamin D (400 IU). After transplantation, serum magnesium decreased by 16 +/- 15% (SD) from 2. 0 +/- 0.3 mg/dl to 1.6 +/- 0.2 mg/dl (normal 1.8-2.2 mg/dl; p < 0. 0001), accompanied by an increase in the fractional excretion of magnesium (7.1 +/- 3.9% to 13.3 +/- 5.6%; p < 0.0017). Forty-three patients with low 3-month serum magnesium levels (相似文献   

Clinicopathologic manifestations of Epstein-Barr virus-associated cutaneous lymphoproliferative disorders

OBJECTIVE: To elucidate clinicopathologic manifestations of cutaneous lymphoproliferative disorders associated with Epstein-Barr virus (EBV) infection. DESIGN: Retrospective survey of case series. SETTING: University hospital medical center. PATIENTS: Sixty-five patients with cutaneous lymphomas and related disorders. MAIN OUTCOME MEASURES: Detection of EBV genes and EBV-encoded small nuclear RNAs. RESULTS: Evidence of latent EBV infection was demonstrated in 15 patients: 3 had malignant lymphoma with clinical features mimicking cytophagic histiocytic panniculitis, 6 had facial vesiculopapular eruptions mimicking hydroa vacciniforme, 4 had angiocentric lymphoma, 1 had histiocytoid lymphoma associated with hemophagocytosis, and 1 had plasmacytoma. Hypersensitivity to mosquito bites was noted in a patient with hydroa vacciniforme-like eruptions and another with histiocytoid lymphoma. Angiocentric infiltration of atypical lymphoid cells was a common histological feature in the patients with hydroa vacciniforme-like eruptions and angiocentric lymphoma. No evidence of EBV infection was apparent in 19 patients with mycosis fungoides or Sézary syndrome, 7 with adult T-cell leukemia or lymphoma, 3 with lymphomatoid papulosis (type A), and 2 with lymphocytoma cutis. CONCLUSION: Patients with EBV-associated cutaneous lymphoproliferative disorders present with unique and diagnostic clinicopathologic features distinct from those of mycosis fungoides or Sézary syndrome.     

Fracture after cardiac transplantation: a prospective longitudinal study

Cardiac transplantation is associated with increased prevalence of vertebral fractures, but the natural history of and risk factors for fracture after this life-saving procedure are unclear. We evaluated 47 patients (34 men and 13 postmenopausal women) before transplantation with spinal radiographs, determination of bone density by dual energy x-ray absorptiometry, and measurement of biochemical indexes of mineral metabolism. During the first year after transplantation, incident fractures were documented radiographically. Associations among demographic characteristics, bone density, biochemistries, and fracture risk were evaluated with logistic regression analysis. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day), 17 patients (7 women and 10 men) sustained a total of 34 fractures. Most fractures involved the spine, and 85% of the patients who experienced fracture did so within 6 months of transplantation. Fifty-four percent of the women and 29% of the men experienced fracture. Femoral neck bone mineral density was significantly lower in women who experienced fracture than in those who did not (0.604 +/- 0.11 vs. 0.760 +/- 0.12 g/cm2; P < 0.04), but did not differ in men according to fracture outcome. The amount of bone loss at the femoral neck by 6 months after transplantation was significantly greater in men with fracture than in men without fracture (12.0 +/- 6.4% vs. 6.8 +/- 5.3%; P < 0.04), but did not differ in women according to fracture outcome. Pretransplant 1,25-dihydroxyvitamin D levels were significantly lower (25 +/- 9 vs. 39 +/- 17 pg/mL; P < 0.007) and intact PTH levels tended to be higher in men who did not experience fracture (37 +/- 15 vs. 69 +/- 46 pg/mL; P < 0.06). Individual pretransplant bone density measurements demonstrated substantial overlap between patients who did and did not experience fracture, and normal bone density did not necessarily protect against fracture after transplantation. We conclude that fractures are a common and early complication of cardiac transplantation. No pretransplant measurement has yet been identified that reliably predicts fracture after transplantation in the individual patient.