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PubMed2002

Acute tonsillitis as the first manifestation of post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication that may follow orthotopic liver transplantation (OLT) in children. The first symptoms are often in the ear, nose, or throat (ENT) area. This abnormal proliferation of lymphoid cells is related to Epstein-Barr virus (EBV) infection in immunocompromised children. The incidence of PTLD, EBV status before OLT and at the diagnosis of PTLD, delay between OLT and PTLD, localization, pathological investigations, and the treatment and evolution of PTLD were prospectively evaluated in 77 pediatric liver transplant recipients. Eight patients (10%) developed PTLD, all with an ENT presentation. Seven had acute nonbacterial tonsillitis (with a negative throat swab), and 1 had a pharyngolaryngeal localization at the time of the diagnosis. Four patients had associated involvement outside the ENT area. All patients were EBV-seronegative at the time of OLT; 6 underwent seroconversion at the time of diagnosis, and 2 within 9 and 20 months of diagnosis. All patients presented with low-grade PTLD. All patients with acute tonsillitis associated with EBV seroconversion underwent immediate tonsillectomy, and immunosuppression was decreased as much as tolerated. This therapeutic protocol led to complete recovery in all patients. After OLT in children, nonbacterial tonsillar inflammation or hypertrophy associated with an EBV infection is often the first manifestation of PTLD. Tonsillectomy combined with tapering of immunosuppression offers the best chance for a complete recovery.

Acute Disease↗

PubMed2005

Genetic heterogeneity of the hypervariable region I of Hepatitis C virus and lymphoproliferative disorders.

B-cell lymphoproliferative disorders (BCLD) have been associated with chronic hepatitis C virus (HCV) infection. The HCV glycoprotein E2 (gpE2) hypervariable region I (HVR-I) may be a potential antigenic candidate to promote B-cell proliferation. The purpose of this study was to analyze the influence of HVR-I sequence variability in the development of BCLD. HVR-I sequences were studied in 29 chronically HCV-infected patients with (n=15) or without (n=14) BCLD. After PCR amplification of the gpE2 region, analysis of the 81 bp HVR-I encoding fragment was performed on 7-18 clones per patient. HVR-I sequence complexity was slightly lower in patients with BCLD (mean 0.347) than without (0.468) (P=0.2), though, sequence diversities were similar (0.0370 vs 0.0954, P=0.239). Phylogenetic analysis did not reveal any BCLD-associated clustering. In our population, neither the recently described insertion between positions 1 and 2 of HVR-I nor residues at positions 4 and 13 were particularly linked to BCLD. As previously described, we confirm the high degree of conservation of HVR-I residues T-2, G-6 and G-23 in our patients. Contrary to recent findings, our analysis based on multiple clones per patient analysis did not reveal any particular motif associated with BCLD.

Adult↗

PubMed2004

Evaluation of histogenesis of B-lymphocytes in pediatric EBV-related post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disorders (PTLD) are morphologically/clinically heterogeneous. The main goal of this study was to define the histogenesis of PTLD (B-cell phenotype, EBV-related) in seven pediatric patients after allogeneic T-cell-depleted bone marrow transplantation. Immunohistochemical stains using histogenetic markers, including Bcl-6 (expressed by germinal center (GC) B cells), MUM1/IFR4 (late GC and post GC B cells), and CD138 (post GC B cells), were performed on paraffin-embedded tissue. By morphology, four cases were classified as polymorphic PTLD and three as monomorphic PTLD, according to the WHO classification. By the expression pattern of histogenetic markers, five cases (two polymorphic, three monomorphic PTLD) were of late GC/early post GC B-cell origin expressing only MUM1/IRF4. The remaining two cases (one monomorphic, one polymorphic PTLD) were of post GC B-cell origin expressing MUM1/IRF4 and CD138, but not Bcl-6. Our study indicates that histogenesis of PTLD may be defined by histogenetic markers using immunohistochemistry. The results suggest that most pediatric PTLD are of late GC/early post GC B-cell origin, and a minor group is of post GC B-cell origin. The histogenesis of PTLD appears independent of morphologic appearance. Further studies are warranted to confirm our observation and to evaluate the clinical significance of histogenetic pattern of PTLD.

Adolescent↗

PubMed2003

Epstein-Barr virus (EBV) load and interleukin-10 in EBV-positive and EBV-negative post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disorders (PTLDs) are heterogeneous severe complications occurring in 1-10% of transplanted patients. In most cases, PTLDs are associated with Epstein-Barr virus (EBV) infection but, recently, some clinical studies have reported an increasing number of EBV-negative PTLDs. Several studies have emphasized the critical role of the early identification of patients at risk for PTLD, in prompting the adoption of either pre-emptive strategies or timely treatment. To this purpose, monitoring of EBV DNA load in peripheral blood mononuclear cells is considered to be a useful test. Moreover, recently, the role of interleukin (IL)-10 in EBV-related diseases has been remarked, and high levels of IL-10 have been detected in PTLD patients. In this study, both EBV load and IL-10 were monitored in 38 PTLD patients at diagnosis and during follow-up, as well as in a control group, in order to establish the diagnostic role of the two tests, their relationship with the different PTLD subsets (EBV-positive and EBV-negative) and their behaviour during treatment. Results of our study suggest that the usefulness of IL-10 assay for early diagnosis of PTLD is similar to that of EBV load quantification, and its clinical diagnostic value is lower in EBV-negative than in EBV-positive PTLDs.

Adult↗

PubMed2003

Latent membrane protein 1, tumor necrosis factor receptor-associated factor (TRAF) 1, TRAF-2, TRAF-3, and nuclear factor kappa B expression in posttransplantation lymphoproliferative disorders.

CONTEXT: Most posttransplantation lymphoproliferative disorders (PTLDs) are associated with Epstein-Barr virus (EBV) infection. The EBV latent membrane protein 1 (LMP-1) is important in the transformation of B lymphocytes through its interaction with intracellular tumor necrosis factor receptor-associated factors (TRAFs) that, in turn, can activate transcription factors such as nuclear factor kappa B (NFkappaB) and Jun-N-kinase. Of the 6 members of the TRAF family, TRAF-1, TRAF-2, and TRAF-3 are most commonly associated with LMP-1. Recently, it has been suggested that LMP-1-induced TRAF activation is important in the pathogenesis of PTLDs. OBJECTIVE: To characterize the expression patterns of these proteins in PTLDs, we studied a series of well-characterized cases for expression of LMP-1, TRAF-1, TRAF-2, TRAF-3, and NFkappaB by immunohistochemical analysis. METHODS: A total of 27 specimens from 25 patients were analyzed for LMP-1, TRAF-1, TRAF-2, TRAF-3, and NFkappaB (active form) by immunohistochemical analysis. Expression of EBV-encoded RNA (EBER) was evaluated by in situ hybridization. Correlation between the expression of the different markers was performed using the Mantel-Haenszel chi(2) test. Cox proportional hazards analysis and Kaplan-Meier analysis with log-rank testing were used to analyze antigen expression and clinical outcome. RESULTS: Ninety-six percent of PTLDs expressed NFkappaB, 74% to 84% expressed TRAFs, 78% expressed EBER, and 77% expressed LMP-1. TRAF-1, TRAF-2, and TRAF-3 expression did not correlate with either EBER or LMP-1 expression. TRAF-2, but not TRAF-1 or TRAF-3, expression correlated with NFkappaB expression (P =.02). CONCLUSIONS: These results suggest that TRAF molecules and active NFkappaB are expressed in PTLDs regardless of EBV positivity. Given the association of TRAF-2 and active NFkappaB expression, TRAF-2 may play an important role in regulating this transcription factor in PTLD.

Bone Marrow Transplantation↗

PubMed2003

A single-centre experience of post-renal transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) complicates 1 to 10% of all transplantations. Previous clinicopathological studies of PTLD have been limited by small numbers, short follow-up times, outdated data, heterogeneity of pooled solid-organ transplant results, and selective inclusion of early-onset disease. We therefore undertake here a retrospective analysis and identify all cases of PTLD that complicated renal transplantation at the Princess Alexandra Hospital between 30 June 1969 and 31 May 2001. Tumour samples were subsequently retrieved for pathological review and for Epstein-Barr virus-encoded RNA in situ hybridisation (EBER-ISH). Of 2,030 renal transplantation patients, 29 (1.4%) developed PTLD after a median period of 0.5 years (range 0.1 to 23.3 years). PTLD patients were more likely to have received cyclosporine (76% versus 62%, P<0.05), tacrolimus (10% versus 2%, P<0.05) and OKT3 (28% versus 10%, P<0.01). As the burden of immunosuppression increased from dual, to triple, to OKT3 therapy, the risks of early onset, extensive-stage, polymorphic, Epstein-Barr virus (EBV)-associated and fatal PTLD progressively increased. The majority of patients presented with an extra-nodal mass (45%), were afebrile (76%), and had stage-IV disease (60%). EBER-ISH was positive in 58%. Actuarial 5-year disease-free survival was 53.7%. The independent predictors of mortality on multivariate Cox regression were polymorphic histology (HR 7.4, 95% CI 1.5-37) and an international prognostic index (IPI) >1 (HR 2.7, 95% CI 1.1-6.8). Compared with other treatments, chemotherapy was associated with higher survival rates (100% versus 18% at 3 years, P=0.0001). In conclusion, PTLD is more likely, occurs earlier, and is more often fatal, in the setting of intensive immunosuppression. Nevertheless, excellent long-term outcomes are achievable with early recognition and institution of appropriate treatment.

Humans↗

PubMed2002

Clinicopathologic characteristics of post-transplant lymphoproliferative disorders.

Post-transplant lymphoproliferative disorder (PTLD) is a syndrome of uncontrolled lymphoid growth in the immunosuppressed transplant patient. Known risk factors include Epstein-Barr virus (EBV) seronegativity at the time of transplant, pediatric age and allograft type. Newer studies suggest that constitutional factors such as cytokine gene polymorphisms may also predispose to PTLD. Although PTLD may occur at any time, the majority of cases arise within the first two post-transplant years. Clinical presentation is heterogeneous and dependent upon the location and extent of disease. Allograft involvement is common, particularly in cases of lung, intestine, or pancreas transplantation. Most PTLD are of B lymphocyte origin. A histopathologic classification system has been proposed and it is important to understand the histology of these lesions, since the term PTLD incorporates both hyperplastic and neoplastic growths. Histologic subclassification also has prognostic value, although this remains imperfect at present. Clinical evaluation should include staging as for lymphomas, since PTLD stage is an important determinant of outcome. In EBV-associated PTLD, quantitative evaluation of EB viral genomic load has a role in guiding prophylaxis, diagnosis, and monitoring of therapy. The presence of EBV is not an absolute requirement for the diagnosis of PTLD, and it has been suggested that there has been a recent increase in the number of EBV-negative cases. Such lesions have a median onset time around 50-60 months post-transplant. Therapy of PTLD must be tailored to the individual patient. Newer modalities such as anti-CD20 antibodies are being evaluated and may complement the standard stepwise approach that begins with a reduction of immunosuppression. The role of chemotherapy continues to be defined, and in some cases early recourse to this approach may be desirable. Survival varies by age and extent of disease, with pediatric patients and those with localized disease tending to fare better. A finer understanding of the molecular cellular and virologic underpinnings of PTLD remains essential in order to define optimal treatment regimens. The emergence of EBV-negative PTLD is a problem and the relationship of this to standard lymphomas arising in nonimmunosuppressed patients remains to be defined. Continued individual and multi-institutional studies are essential for progress in these areas.

Epstein-Barr Virus Infections↗

PubMed2004

Prevalence of hepatitis C virus in lymphoproliferative disorders.

OBJECTIVE: To study the prevalence of hepatitis C virus in lymphoproliferative disorders. METHODS: A case control prospective study was performed on 143 patients with lymphoproliferative disorders and 29 patients with non-hematological malignancies were taken as controls. All the patients in both groups were analyzed for various risk factors for infection with hepatitis C virus and were tested for the presence of hepatitis C virus antibody (anti HCV), cryoglobulins and rheumatoid factor antibody. Hepatitis C viremia was documented by detection of HCV RNA by polymerase chain reaction. RESULTS: There was no significant difference for risk factors for hepatitis C virus infection in both the groups except for the increase in number of surgical procedures being carried out in the control group. There was no significant difference in the presence of rheumatoid factor antibody in both the groups and cryoglobulins were not positive in any individual. Five percent patients with lymphoproliferative disorders and 3.4% with non-hematological malignancies were positive for anti HCV. HCV RNA was detected in 29.2% cases and 31.0% in controls. CONCLUSION: There was no association between hepatitis C virus infection and lymphoproliferative disorder in our population. However, further studies are required from this region to establish any causal relationship between hepatitis C virus infection and lymphoproliferative disorder.

Adolescent↗

PubMed2000

Lymphoproliferative disorders presenting as mediastinal neoplasms.

Lymphoproliferative disorders may present in any organ of the body. The mediastinum is an uncommon location for presentation of these heterogeneous disorders, but involvement of the mediastinum may be the sole site of disease for several aggressive lymphomas. Both Hodgkin's disease and non-Hodgkin's lymphoma may present in the mediastinum. The most common types of non-Hodgkin's lymphoma involving the mediastinum include lymphoblastic lymphoma and mediastinal large cell lymphoma. These lymphomas most commonly develop in the anterior mediastinum but may be seen in the middle and posterior mediastinum. Symptoms associated with a mediastinal presentation of a lymphoproliferative disorder are often attributable to compression of mediastinal structures (eg, superior vena cava syndrome) or invasion of thoracic structures such as the pericardium or pleura. Although staging can be performed with routine imaging studies, surgical intervention is often required to ensure accurate histologic diagnosis of these lymphomas. Once a diagnosis has been established, therapeutic modalities usually include chemotherapy and/or radiotherapy.

Humans↗

PubMed1992

Study of the major phenotype of large granular T-cell lymphoproliferative disorder.

Six cases of large granular T-cell lymphoproliferative disorder with a selected immunophenotype (CD3+, CD4-, CD8+, CD16+) were studied to characterize a homogeneous group of patients. It was found that most of these patients did not exhibit the clinical features frequently described in large granular T-cell lymphoproliferative disorder--recurrent infection, rheumatoid arthritis, and splenomegaly. The laboratory tests usually positive in large granular T-cell lymphoproliferative disorder, including rheumatoid factor and anti-nuclear antibodies, also were frequently negative. The pathognomonic features were found to be neutropenia and large granular lymphocytosis with positive killer cell markers. All six cases showed T-cell receptor gene rearrangement that indicated a monoclonal proliferation of lymphoid cells, which were natural killer-like T cells by immunophenotyping. B cells were essentially absent in all cases. It should be emphasized that bone marrow aspirates are as informative as peripheral blood samples for the diagnosis of large granular T-cell lymphoproliferative disorder; indeed, phenotypes of blood and marrow in one case were identical in terms of percentages of markers. In this selected group of patients, the clinical courses were indolent with uncomplicated outcomes. In three patients, chemotherapy did not induce an obvious clinical response, but all patients' conditions remained stable with only supportive care.

Adult↗

PubMed1998

The changing incidence of lymphoproliferative disorders in Yorkshire.

Secular trends in the incidence of lymphoproliferative disorders on North and West Yorkshire and Humberside from 1985 to 94 were studied and changes in incidence by tumour subtype were analysed. Population-based data on the incidence of lymphoproliferative disorders were obtained from a specialist registry with a high level of ascertainment. Cases of chronic lymphocytic leukaemia and plasma cell myeloma were excluded and the remaining cases classified as Hodgkin's disease and non-Hodgkin's lymphoma (NHL). NHL were subdivided by site of origin and immunophenotype. Nodal B-cell lymphomas were further classified as diffuse large B-cell lymphoma, follicle centre lymphoma, mantle cell lymphoma and miscellaneous. During the study period there was a significant increase in total lymphoproliferative disorders with an average change of 2.5% per annum equivalent to 0.84/10,0000. Most of this increase was due to an increasing incidence of extranodal B-cell lymphomas and peripheral T-cell lymphomas. A numerically small but significant increase in diffuse large B-cell lymphomas was seen. There was no significant increase in other subtypes. The increased incidence of lymphomas in the area studied is mainly due to changes in two specific subgroups. There are several reasons why changes in extranodal B-cell lymphoma and peripheral T-cell lymphoma may have been particularly affected by changing diagnostic practices. Epidemiological studies of particular subtypes of lymphoproliferative disorder facilitate the identification of environmental factors involved in the pathogenesis of these tumours.

Adolescent↗

PubMed2006

The impact of the World Health Organization classification and clonality assessment of posttransplant lymphoproliferative disorders on disease management.

CONTEXT: The World Health Organization classification of posttransplant lymphoproliferative disorders divides them into 4 main categories. OBJECTIVE: To classify cases of posttransplant lymphoproliferative disorders diagnosed in our institution according to the World Health Organization scheme and correlate the classification and clonality with clinical data. DESIGN: Cases of posttransplant lymphoproliferative disorders were reviewed. They were classified according to the World Health Organization scheme. Clonality was determined by flow cytometry and/or polymerase chain reaction. Patients' charts were reviewed. RESULTS: Thirty-one cases were identified. Median age was 33 years. There were 19 cases of kidney, 8 cases of liver, and 4 cases of bone marrow transplant. Immunosuppression consisted of cyclosporin A and prednisone (N = 24) or FK506 and prednisone (N = 7). Twenty cases (63%) were World Health Organization type 3, 7 cases (23%) type 2, 3 cases (6.4%) type 1, and 1 case type 4 posttransplant lymphoproliferative disorder. Ten patients received chemotherapy, 20 patients had reduction of immunosuppression, and 1 had no treatment. Follow-up was available on 25 patients. Seven (43.75%) of 16 with type 3 lesions with available follow-up died of their disease. Five of these patients received reduction of immunosuppression alone. Only 2 of 9 patients with type 3 disease who received chemotherapy died of disease. Two patients with type 2 disease died of unrelated causes. One patient is alive with disease; the remaining patients with types 1 and 2 disease are alive with no disease. CONCLUSIONS: The World Health Organization classification of posttransplant lymphoproliferative disorders is valuable in the identification of subtypes. It helps identify early lesions (1 and 2) requiring reduction of immunosuppression and type 3 disease, which requires chemotherapy from the outset.

Adolescent↗

PubMed2004

[Acquired C1 inhibitor deficiency associated with lymphoproliferative disorders: four cases].

INTRODUCTION: Acquired C1 inhibitor deficiency is sometimes associated with lymphoproliferative disorders. EXEGESIS: We report four cases of acquired C1 inhibitor deficiency in association with lymphoproliferative disorders. Three of them were asymptomatic; one was associated with abdominal pain. Four women (median age, 66 years) presented either two non-Hodgkin lymphoma or two chronic lymphocytic leukaemia. C1 inhibitor deficiency was detected fortuitous (n = 1) or during investigation of arthralgia (n = 2), or Gougerot-Sjogren syndrome (n = 1). The deficit was acquired in all cases type I. Auto-immune disorders were associated with: Gougerot-Sjogren syndrome (n = 1), cryoglobulinemia (n = 2), IgM lambda monoclonal gammopathy (n = 1), Coombs positive test (n = 2), IgG anti-cardiolipine antibodies (n = 1). C1 inhibitor deficiency was not modified after lymphoproliferative disorders treatment (radiotherapy, splenic ablation) in two cases but patients were not in complete remission. C1 inhibitor raised normal level in one case, after five chemotherapy regimens, but decreased complement level and C4 split persist. CONCLUSION: Acquired C1 inhibitor deficiency associated with lymphoproliferative disorders is sometimes asymptomatic. Diagnosis could be delay in spite of clinical manifestations. Deficit correction is not constant after lymphoproliferative disorders treatment.

Aged↗

PubMed1993

Posttransplantation lymphoproliferative disorders treated with cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy.

BACKGROUND: Posttransplantation lymphoproliferative disorders after solid organ transplantation are a serious complication occurring in 1-10% of patients. Different therapies have been used, but the optimal treatment is unknown. There is relatively little information in the literature on the experience with cytotoxic chemotherapy. METHODS: The disease stage of patients with biopsy-documented posttransplantation lymphoproliferative was determined with standard methods to establish the extent of the disease. Patients in whom the disease failed to regress after initial management, which included reduction in immunosuppression, were treated with a combination chemotherapy regimen consisting of six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Response to therapy was determined by following previously defined sites of disease with appropriate tests. Patients were maintained on a reduced dose of immunosuppressants. RESULTS: In the four patients studied, lymphoproliferative disorders developed after heart (three cases) or lung (one case) transplantation, which did not regress after immunosuppression was reduced. All four experienced a complete remission with CHOP chemotherapy, which continued at 3, 13+, 20 and 30+ months after completion of treatment. One patient died of sepsis after completing therapy at a point when his leukocyte count was normal, and no evidence of posttransplantation lymphoproliferative disorder was found at autopsy. A second patient died of liver failure with no clinical evidence of lymphoproliferative disorder. CONCLUSION: Although this is a small series, it demonstrates that patients with posttransplantation lymphoproliferative disorders may respond to cytotoxic chemotherapy. The duration of response is undetermined.

Adult↗

PubMed1991

Hepatitis B surface antigenaemia in patients with malignant lymphoproliferative disorders.

One hundred and four patients with malignant lymphoproliferative disorders and 5,690 control subjects were screened for the presence of Hepatitis B surface antigen (HBsAg) in their sera. Lymphoproliferative disorders included in the study were acute lymphoblastic leukaemia (ALL), non Hodgkin's Lymphoma (NHL), chronic lymphocytic leukaemia (CLL), Hodgkin's disease (HD), Burkitt's lymphoma (BL) and multiple myeloma (MM). Screening was done by the Reverse Passive Haemagglutination method using the Welcome kit. The percentage antigenaemia in the patients and control subjects were 35.6 and 7.7% respectively (p less than 0.0001). Using the Odds ratio the relative risk was found to be 6.75. The Odds ratio for individual disorders ranged from 2.8 to 9.17. The results suggest an association between Hepatitis B surface antigenaemia and malignant lymphoproliferative disorders and highlights the risk involved in handling specimens from the patients.

Adolescent↗

PubMed1993

Chronic lymphoproliferative disorders: classification and diagnosis.

The chronic lymphoproliferative disorders are morphologically, immunologically and clinically heterogeneous. Common features of these processes include T, B or natural killer cell immunophenotypes and terminal deoxy-nucleotidyl transferase negativity. The B cell lymphocytic disorders include B-chronic lymphocytic leukaemia, B cell prolymphocytic leukaemia, chronic lymphocytic leukaemia-prolymphocytic leukaemia, non-Hodgkin's lymphoma (including mantle cell lymphoma) in leukaemic phase, hairy cell leukaemia and splenic lymphoma with villous lymphocytes. The T cell chronic lymphoproliferative disorders include prolymphocytic leukaemia, adult T cell leukaemia-lymphoma, large granulated lymphocyte leukaemia and Sézary syndrome. Occasionally, a lymphocytic proliferation is encountered that does not satisfy the morphological or immunophenotypical criteria for any of the above categories. These processes are best left unclassified.

Adult↗

PubMed1998

Abdominal manifestations of posttransplantation lymphoproliferative disorder.

The abdominal manifestations of posttransplantation lymphoproliferative disorder show wide variability with potential involvement of all organ systems. The radiologist should be aware of this entity when evaluating patients who have undergone transplantation; both clinical and radiologic findings can mimic other disease processes. Suggestive lesions should prompt a search for additional areas of involvement. In our experience, although sonography can reveal posttransplantation lymphoproliferative disorder of the abdominal viscera, CT more adequately depicts the full extent of disease involvement. Distinguishing between monomorphic and polymorphic subtypes, though important for treatment planning, is not possible by imaging characteristics alone. Therefore, tissue diagnosis is warranted.

Adolescent↗

PubMedDate not supplied

Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantations.

BACKGROUND: The relative importance and interrelationship of risk factors for posttransplantation lymphoproliferative disorder are poorly understood. METHODS: The prospective pretransplantation serologic testing for Epstein-Barr virus of all nonrenal solid organ transplant recipients at our institution made it possible to assess the relative risk for posttransplantation lymphoproliferative disorder in seropositive and seronegative recipients. RESULTS: Fourteen cases of lymphoproliferative disorder were identified in the first 389 consecutive transplant recipients (288 liver, 44 heart, 20 lung, 37 kidney-pancreas) undergoing transplantation from 1985 to 1992 (mean follow-up 33 months). The incidence rates of lymphoproliferative disorder (per 100 person-years) during the first 2 years after transplantation (a period in which all cases occurred) were 1.4 for liver, 2.0 for heart, 6.2 for lung, and 5.2 for kidney-pancreas transplant recipients and were significantly different between liver and lung (p = 0.005) and liver and kidney-pancreas (p = 0.002) groups. Of 367 seropositive patients, lymphoproliferative disorder developed in only three. The incidence rate ratios between seronegative and seropositive recipients were as follows: 76 ([95% confidence interval; 46, 144], p = 0.0000) for any form of lymphoproliferative disorder and 145 ([60, 347], p = 0.0000) for fatal or brain forms. The incidence rate of lymphoproliferative disorder was significantly higher for seronegative recipients who required antilymphocyte antibody therapy for rejection than for those who received none. CONCLUSIONS: The high intrinsic risk for lymphoproliferative disorder in the Epstein-Barr virus seronegative patient, which is amplified by higher levels of immunosuppression, may, in some instances, preclude transplantation.

Acyclovir↗