mercaptopurine and Epstein-Barr-Virus-Infections

Topics: Aged; Colitis, Ulcerative; Endoscopy; Epstein-Barr Virus Infections; Humans; Magnetic Resonance Imaging; Male; Mercaptopurine; Rectum; Time Factors

The lymphoproliferative disorders (LDs) are a heterogeneous group of at least 70 conditions that result from the clonal proliferation of B, T, and NK cells. Inflammatory bowel disease (IBD)-associated lymphomas are typically B-cell LD, while T-cell or Hodgkin's lymphomas are rare. In IBD patients not on immunosuppression, the risk of LD seems to be similar or slightly higher than the background population risk. Thiopurine therapy is associated with an increased risk: the relative risk is increased four- to sixfold and the absolute risk varies between 1 in 4000-5000 for those aged 20-29 to 1 in 300-400 in those over 70. It is difficult to quantify the risk of anti- tumor necrosis factor (TNF) therapy alone; however, it appears to be less than for thiopurines alone. There is particular concern regarding the development of post-transplant-like LD in those with latent epstein-barr virus (EBV) infection exposed to immunosuppressives, the occurrence of hepatosplenic T cell lymphoma in patients treated with combination anti-TNF and thiopurine therapy, and the development of hemophagocytic lymphohistiocytosis in those who acquire a primary EBV or other infections while on immunosuppressive medication. There are currently no guidelines for monitoring EBV (or other virus) status in patients on immunosuppression, although it could be used to monitor those who have a prior history of lymphoma and are about to start a thiopurine or anti-TNF agent. In discussing the risks of lymphoproliferative disorders associated with agents used for the treatment of IBD, patients can often be reassured that the benefits of such therapy still outweigh the small, but real, risks.

Topics: Age Factors; Azathioprine; Epstein-Barr Virus Infections; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphohistiocytosis, Hemophagocytic; Lymphoma; Lymphoproliferative Disorders; Mercaptopurine; Risk Factors; Tumor Necrosis Factor-alpha

Topics: Child; Encephalitis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Infliximab; Mercaptopurine

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication.

Topics: Adalimumab; Anti-Inflammatory Agents; Crohn Disease; Epstein-Barr Virus Infections; Humans; Immunologic Factors; Immunosuppressive Agents; Lymphohistiocytosis, Hemophagocytic; Male; Mercaptopurine; Rituximab; Young Adult

Epstein Barr virus (EBV) is a human herpes virus that infects 90% of the world's population and has been linked to the development of lymphoproliferative disorders (LPDs) and immunosuppression. Primary EBV infection in patients with IBD on thiopurines is a risk factor for LPD, including lymphoma. We aimed to describe EBV status in a pediatric population with IBD with an emphasis on those initiating thiopurines.. Electronic medical records and EBV serologies were reviewed and categorized into asymptomatic screening versus suspicion for acute infection. EBV status before therapy was described by sex, age, and therapeutic regimen. Descriptive statistics and univariate analysis were employed.. Only 150 (22%) of our 688 pediatric patients with IBD had documented EBV status regardless of age or treatment regimen. Only 17% were assessed for suspicion of acute infection and 83% for screening. Sixty-four (52%) screened patients were checked before starting any treatment and only 40% were immunoglobulin (Ig)G positive. There was no difference in mean age between the seronegative and seropositive group. The majority (63%) of thiopurine-treated patients were IgG negative before starting therapy. Eighty percent of primary EBV infections occurred on thiopurines at a mean (SD) of 2 ± 1.5 years after initiating therapy.. The majority of our pediatric patients with IBD with documented EBV status were IgG negative at thiopurine initiation. Thiopurines were also associated with primary EBV infection. EBV status may be an important determinate of whether physicians prescribe thiopurines given the risk of primary EBV infections and lymphoproliferative diseases.

Topics: Adolescent; Child; Cross-Sectional Studies; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; New York City; Retrospective Studies; Viral Load; Young Adult

We describe a 4-year-old female with pre-B-cell acute lymphoblastic leukemia on maintenance chemotherapy, who developed hemophagocytic lymphohistiocytosis (HLH) secondary to Epstein-Barr virus (EBV) infection, complicated by an aggressive lymphoproliferative disorder. Although there was no history of bone marrow transplant or underlying immunodeficiency, EBV triggered a post-transplant lymphoproliferative disease (PTLD)-like lymphoma. Multiple regimens of chemotherapy failed to induce remission and patient developed multiorgan failure. The association of HLH with EBV-related PTLD-like lymphoproliferative disorder is rare. We present this case to highlight this unusual association so that this highly fatal disease can be recognized and promptly addressed.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cyclosporine; Dexamethasone; Epstein-Barr Virus Infections; Etoposide; Female; Humans; Immunocompromised Host; Infant; Lymphohistiocytosis, Hemophagocytic; Male; Mercaptopurine; Methotrexate; Multiple Organ Failure; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rituximab; Treatment Failure; Vincristine; Viral Load

The setting of chronic immunosuppression in inflammatory bowel disease (IBD) may promote the proliferation of Epstein-Barr virus-positive neoplastic clones. We report two rare cases of Epstein-Barr virus-associated lymphoproliferative disorder in IBD patients: one resembled lymphomatoid granulomatosis, and the other was a lymphoma resembling Hodgkin lymphoma. There are currently no guidelines for the prevention of lymphoproliferative disorder in IBD patients on immunosuppressive therapy.

Topics: Adult; Chronic Disease; Epstein-Barr Virus Infections; Fatal Outcome; Female; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoproliferative Disorders; Male; Mercaptopurine

To assess the incidence of hemophagocytic lymphohistiocytosis (HLH) in a well-defined population of children with inflammatory bowel disease (IBD) and evaluate the common clinical and laboratory characteristics of individuals with IBD who developed HLH.. We conducted a retrospective study of all children who developed HLH over an 8-year period. The incidence of HLH in patients with IBD was calculated using US census data and a statewide project examining the epidemiology of pediatric IBD.. Among children in Wisconsin, 20 cases of HLH occurred during the study period; 5 cases occurred in children with IBD. Common characteristics include: Crohn's disease (CD), thiopurine administration, fever lasting more than 5 days, lymphadenopathy, splenomegaly, anemia, lymphopenia, and elevated serum triglycerides and ferritin. Of the patients, 4 had primary Epstein-Barr virus infections. The incidence of HLH among all children in Wisconsin was 1.5 per 100 000 per year. The risk was more than 100-fold greater for children with CD (P < .00001).. Pediatric patients with CD are at increased risk for developing HLH; primary Epstein-Barr virus infection and thiopurine administration may be risk factors.

Topics: Adolescent; Anemia; Azathioprine; Crohn Disease; Epstein-Barr Virus Infections; Ferritins; Fever; Humans; Immunosuppressive Agents; Incidence; Lymphatic Diseases; Lymphohistiocytosis, Hemophagocytic; Lymphopenia; Mercaptopurine; Retrospective Studies; Splenomegaly; Triglycerides; Wisconsin

Immune suppressant medications such as thiopurines and anti-tumor necrosis factor agents are important for maintaining disease control in most patients with inflammatory bowel diseases (IBDs); however, their use has been associated with the development of malignant lymphoma. The purpose of this Dutch nationwide study was to estimate the relative risk of malignant lymphoma in IBD patients.. IBD patients who developed a lymphoma between 1997 and 2004 were identified using the Dutch National Database of PALGA. Data from confirmed cases were collected from individual hospitals, including data on Epstein-Barr virus (EBV). The age-adjusted 8-year incidence of malignant lymphoma in the Netherlands was retrieved from the Central Bureau of Statistics.. Forty-two hospitals were visited and 285 matches evaluated in the total cohort of 17,834 IBD patients. Forty-four lymphomas were observed, resulting in a relative risk of 1.27 (95% confidence interval [CI]: 0.92-1.68). Only 19 of 44 patients (43%) were exposed to azathioprine/6-mercaptopurine (AZA/6-MP). Remarkably, 92% of patients (11/12) with EBV-positive lymphoma used AZA/6-MP, in contrast to only 19% patients (4/21) with EBV-negative lymphoma, suggesting a strong relation between EBV-positive lymphoma and thiopurine use.. This nationwide study does not suggest a significant overall increased risk for lymphoma in IBD patients. A distinct correlation between EBV-positive lymphoma and AZA/6-MP use was observed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Azathioprine; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Epstein-Barr Virus Infections; Female; Follow-Up Studies; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Incidence; Infant; Infant, Newborn; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; Middle Aged; Netherlands; Prognosis; Risk Factors; Survival Rate; Young Adult

Epstein-Barr virus (EBV) is a herpesvirus for which latent infection in B lymphocytes occurs in most individuals by middle childhood. Clinically significant reactivation of this virus occurs in the context of suppressed cell-mediated immunity, occasionally developing into lymphoproliferative disease (EBV-LPD). EBV reactivation is rarely associated with intensive chemotherapy alone. Here we present the case of a 4-year-old female who developed EBV-LPD as a complication of prolonged immunosuppressive chemotherapy for her multiply-recurrent Langerhans cell histiocytosis (LCH).

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cytarabine; Doxorubicin; Drug Therapy, Combination; Epstein-Barr Virus Infections; Fatal Outcome; Female; Herpesvirus 4, Human; Histiocytosis, Langerhans-Cell; Humans; Immunocompromised Host; Infant; Lymphoma, Large B-Cell, Diffuse; Mercaptopurine; Methotrexate; Mycoses; Prednisone; Recurrence; Rituximab; Vinblastine; Vincristine; Virus Activation

Topics: Aged; Antibodies, Monoclonal; Brain; Brain Neoplasms; Crohn Disease; Diagnosis, Differential; Epstein-Barr Virus Infections; Fatal Outcome; Female; Groin; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Infliximab; Lymph Nodes; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Imaging; Mercaptopurine; Tomography, X-Ray Computed; Unconsciousness

During treatment for inflammatory bowel disease (IBD) 2 men with ulcerative colitis, aged 52 and 38 years, and a 37-year-old man with Crohn's disease developed Epstein-Barr virus (EBV)-related non-Hodgkin's B-cell lymphoma. The first 2 patients underwent proctocolectomy and the use of immunosuppressive agents was discontinued, after which the lymphoma disappeared. The third patient had icterus, hepatosplenomegaly and pancytopenia; he died from multiple organ failure. Azathioprine and 6-mercaptopurine are first choice therapy in the treatment of steroid-refractory IBD. These immunomodulating agents are associated with the development of EBV-positive lymphomas in the setting of solid organ transplantation. This type of lymphoma is a rare complication in IBD, although the incidence in referral centres appears to be increasing. Since azathioprine is an important drug in IBD, there is a need for identification of IBD patients at risk of developing a lymphoma. EBV-DNA in plasma or in faeces may be a candidate tumour marker.

Topics: Adult; Azathioprine; Colitis, Ulcerative; Crohn Disease; Epstein-Barr Virus Infections; Fatal Outcome; Humans; Immunosuppressive Agents; Incidence; Lymphoma, B-Cell; Male; Mercaptopurine; Middle Aged; Risk Factors

The use of azathioprine and 6-mercaptopurine for inflammatory bowel disease increased in the early 1990s. We sought to determine the effect of this change in therapy on the risk of lymphoma in patients with inflammatory bowel disease.. All patients with inflammatory bowel disease at a single tertiary care medical center who developed lymphoma between 1985-2000 were identified and the pathologic features of the lymphoma including presence of Epstein- Barr virus were determined. The patients were divided into two 8-year periods (1985-1992, 1993-2000) corresponding with the introduction of azathioprine and 6-mercaptopurine in 1993.. Eighteen patients with lymphoma were identified, 6 between 1985-1992 and 12 between 1993-2000. Six of 18 lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine, all between 1993-2000. Seven patients developed Epstein-Barr virus-positive lymphoma (1 from 1985-1992, 6 from 1993-2000). Five of 7 Epstein-Barr virus-positive lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine compared with 1 of 11 Epstein-Barr virus-negative lymphomas (P = 0.01). Approximately 1200 patients with inflammatory bowel disease were treated with these agents between 1993-2000.. Treatment of inflammatory bowel disease with azathioprine or 6-mercaptopurine appears to be associated with a small increased risk of Epstein-Barr virus-positive lymphoma.

Topics: Adult; Aged; Aged, 80 and over; Azathioprine; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Lymphoma; Male; Mercaptopurine; Middle Aged; Risk Factors