Risk factors for early-onset and late-onset post-transplant lymphoproliferative disorder in kidney recipients in the United States.
ABSTRACT Solid-organ transplant recipients have an elevated risk for some malignancies because of the requirement for immunosuppression . In particular, non-Hodgkin's lymphoma (NHL) is common and comprises one end of a spectrum of post-transplant lymphoproliferative disorder (PTLD) ranging from benign hyperplasia to lymphoid malignancy . PTLD risk is influenced by the type of organ transplanted, the age and Epstein-Barr virus (EBV) serostatus of the transplant recipient, and the intensity of immunosuppression [3-9]. PTLD incidence is high immediately after transplantation, decreases subsequently, and then rises again 4-5 years from transplantation [10,11]. This incidence pattern suggests the presence of separate early-onset and late-onset PTLD subtypes. Early-onset PTLDs tend to be EBV-positive and, when extranodal, are more likely than late-onset PTLDs to be localized to the transplanted organ [12,13]. Late-onset PTLD is less likely to be associated with EBV and, overall, is more likely than early-onset PTLD to be extranodal [13,14]. The Scientific Registry of Transplant Recipients (SRTR) includes data on a large number of solid-organ transplant recipients in the United States and information on malignancies diagnosed post-transplantation. We used these data to conduct a retrospective cohort study among kidney transplant recipients to examine differences in risk factors between early-onset PTLD and late-onset PTLD.
Article: Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?[show abstract] [hide abstract]
ABSTRACT: Organ recipients are at a high risk of posttransplant lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy. Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV. There were seven kidney, three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outcome were compared with those in 21 patients with EBV-associated PTLD treated in our institution (group II). EBV was detected with at least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1 (LMP1) expression by immunohistochemistry. The time between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean, 546; median, 180), and was significantly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in group I and nine in group II. The survival time was significantly longer in group II (P < .01). EBV-negative PTLD may be a late serious complication of organ transplantation. Half the tumors observed after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.Journal of Clinical Oncology 07/1998; 16(6):2052-9. · 18.37 Impact Factor
Article: Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation.[show abstract] [hide abstract]
ABSTRACT: Non-Hodgkin lymphoma (NHL) incidence is greatly increased after kidney transplantation. NHL risk was investigated in a nationwide cohort of 8164 kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry. NHL diagnoses were ascertained using linkage with national cancer registry records. Multivariate Poisson regression was used to compute incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing risk by transplant function, and risk factors for early (< 2 years) and late (>/= 2 years) NHL during the first transplantation. NHL occurred in 133 patients. Incidence was strikingly lower after transplant failure and cessation of immunosuppression than during transplant function (IRR, 0.25; 95% CI, 0.08-0.80; P = .019). Early NHL (n = 27) was associated with Epstein-Barr virus (EBV) seronegativity at transplantation (IRR, 4.66; 95% CI, 2.10-10.36, P < .001) and receipt of T cell-depleting antibodies (IRR, 2.39; 95% CI, 1.08-5.30; P = .031). Late NHL (n = 79) was associated with increasing year of age (IRR, 1.02; 95% CI, 1.01-1.04; P = .006), increasing time since transplantation (P < .001), and current use of calcineurin inhibitors (IRR, 3.13; 95% CI, 1.53-6.39; P = .002). These findings support 2 mechanisms of lymphomagenesis, one predominantly of primary EBV infection in the context of intense immunosuppression, and another of dysregulated lymphoid proliferation in a prolonged immunosuppressed state.Blood 06/2009; 114(3):630-7. · 9.90 Impact Factor
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ABSTRACT: Non-Hodgkin lymphoma (NHL) includes a group of more than 20 different malignant lymphoproliferative diseases that originate from lymphocytes. Rates of NHL have increased dramatically over the past few decades, although the rate of increase has recently slowed. It is now the sixth most common cancer in Australia. Globally, it is somewhat more common in men than in women, and rates are highest in North America and Australia. The causes of the increase in NHL rates are largely unknown. The best described risk factor for NHL is immune deficiency; rates of NHL are greatly increased, with relative risks of 10-100 or more, in people with immune deficiency associated with immune suppressive therapy after transplantation, HIV/AIDS, and congenital conditions. In addition, some NHL subtypes are associated with specific infections. These include immune-deficiency-associated central nervous system NHL (Epstein-Barr virus); gastric mucosa-associated lymphoid tissue NHL (Helicobacter pylori); adult T-cell leukemia/lymphoma (human T-lymphotrophic virus type 1) and body cavity-based lymphoma (human herpesvirus 8). However, these specific infections account for a very small proportion of total NHL incidence. In addition to immune deficiency and infection, other immune-related conditions are increasingly being recognised as related to NHL risk. Specific autoimmune conditions, including rheumatoid arthritis, systemic lupus erythema, Sjogren's syndrome, psoriasis and coeliac disease are associated with moderately increased risk of NHL. On the other hand, allergic and atopic conditions and their correlates such as early birth order, appear to be associated with a decreased risk of NHL.A variety of other exposures are less strongly related to NHL risk. These include occupational exposures, including some pesticides, herbicides, and solvents. Recently, two studies have reported that sun exposure is associated with a decreased risk of NHL. Smoking appears to be weakly positively associated with risk of follicular NHL, and alcohol intake is associated with a decreased risk of NHL. The pooled analysis of several case-control studies of NHL risk that are currently in the field promises to help clarify which of these risk factors are real, and will contribute to the elucidation of the mechanisms of how disorders of the immune system, and other factors, are related to NHL risk.Pathology 01/2006; 37(6):409-19. · 2.38 Impact Factor