Lymphoma in Cardiac Transplant Recipients Associated with Cyclosporin A, Prednisone and Anti-Thymocyte Globulin (ATG)

Bieber, Charles P.; Heberling, R. L.; Jamieson, Stuart W.; Oyer, P E; Cleary, Michael L.; Warnke, Roger A.; Saemundsen, Ari K.; Klein, George; Henle, Werner; Stinson, E. B.

doi:10.1007/978-1-4684-4760-6_15

Cited by 23 publications

(12 citation statements)

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“…This is significantly different from the proportion of primary EBV infections in a population of patients without tumors (table 1; 3 [8%] of 39, P < .01). This point is not evident from previous reports [4,7].…”

Section: Discussioncontrasting

confidence: 81%

“…Bieber et al [7] reported that 10 (5%) of 200 heart transplant recipients receiving azathioprine, prednisone, and antithymocyte globulin developed lymphomas, whereas five (13%) of 39 developed lymphomas when cyclosporine was substituted for azathioprine. It is likely that the occurrence of such tumors may be decreased by adjustment of cyclosporine doses guided by serum levels [18].…”

Section: Discussionmentioning

confidence: 99%

“…Lane e is a negative control. Lanes f-i contain 5 µg of DNA from each of four patients (7,11,9,8); this is ~ 10 6 cell equivalents of DNA per lane. Thus, samples f, g, and i have 10 copies per cell, and sample h has four copies per cell.…”

Section: Discussionmentioning

confidence: 99%

“…The sensitivity and specificity of IgM antibodies to viral capsid antigen (VCA) and IgG antibodies to early antigen (EA) are also unclear. Most authors have relied on changes in IgG antibody to VCA to diagnose EBV infection in such patients [1,[5][6][7].…”

Section: Ebv Serology and Serological Diagnosismentioning

confidence: 99%

“…Two of their patients developed primary EBV infection, in six the infection reactivated, and 12 had evidence of EBV DNA in their tumors by hybridization studies. Bieber et al [7] reported that five of 39 heart transplant recipients receiving cyclosporine, prednisone, and antithymocyte globulin developed lymphomas. Four tumors were positive for EBV DNA by cRNA-DNA filter hybridization, and three patients had serological evidence of EBV infection.…”

mentioning

confidence: 99%

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Epstein-Barr Virus Infections and DNA Hybridization Studies in Posttransplantation Lymphoma and Lymphoproliferative Lesions: The Role of Primary Infection

Ho¹,

Miller²,

Atchison³

et al. 1985

Journal of Infectious Diseases

431

161

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Fourteen patients who developed B cell lymphomas or lymphoproliferative lesions after kidney, liver, heart, or heart-lung transplantation in Pittsburgh during [1981][1982][1983] had active infection with Epstein-Barr virus (EBV) of the primary (six patients), reactivated (seven patients), or chronic (one patient) type. In transplant patients without tumors, the incidence of EBV infection was 30% (39 of 128). Only three of these patients had primary infections. Thus the frequency of active infection was significantly higher in patients with tumors, and patients with primary infections were at greater risk of developing tumors. Five of 13 tumors tested contained EBV nuclear antigen (EBNA) and nine of 11 contained EBV genomes detected by DNA-DNA hybridization with BamHI K, BamHI W, or EcoRI B cloned probes. All EBNA-positive tumors, except one, were also positive by hybridization. Only one tumor was negative for both EBNA and EBV DNA. These data suggest that EBV plays an etiologic role in the development of these lesions.Epstein-Barr virus (EBV) is a human herpesvirus associated with an array of conditions that range from inapparent infection and infectious mononucleosis to lethal lymphoproliferative syndromes, nasopharyngeal carcinoma, Burkitt's lymphoma, and B cell lymphomas in immunocompromised patients [1]. The precise role of the virus in carcinogenesis is unclear, although in Burkitt's lymphoma the importance of viral transformation of infected B lymphocytes and chromosomal translocations has been emphasized [2]. It is even less clear in lymphomas and lymphoproliferative lesions arising in immuno-compromised patients, where the immunopathology may not be uniform and where chromosomal studies are largely lacking.Recently, we reported on the reversibility of lymphomas and lymphoproliferative lesions in a series of 17 transplant patients after reduction of cyclosporine and steroid immunosuppression [3]. In that preliminary report we noted that seven of these patients had evidence of primary EBV infections and eight had evidence of reactivated infection. Six tumors had evidence of EBV nuclear antigen (EBNA) and seven had evidence of EBV DNA by nucleic acid hybridization. [6] reported the results of studies on 19 renal transplant patients who developed lymphoproliferative disorders and lymphomas after transplantation. All the patients except one were receiving azathioprine, prednisone, and antithymocyte globulin. Two of their patients developed primary EBV infection, in six the infection reactivated, and 12 had evidence of EBV DNA in their tumors by hybridization studies. Bieber et al. [7] reported that five of 39 heart transplant recipients receiving cyclosporine, prednisone, and antithymocyte globulin developed lymphomas. Four tumors were positive for EBV DNA by cRNA-DNA filter hybridization, and three patients had serological evidence of EBV infection.We report here evidence for active EBV infection in all of our patients with tumors and a significantly higher frequency of primary infection than found i...

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Section: Discussioncontrasting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Ebv Serology and Serological Diagnosismentioning

confidence: 99%

mentioning

confidence: 99%

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Epstein-Barr Virus Infections and DNA Hybridization Studies in Posttransplantation Lymphoma and Lymphoproliferative Lesions: The Role of Primary Infection

Ho¹,

Miller²,

Atchison³

et al. 1985

Journal of Infectious Diseases

431

161

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Lymphomas following cardiac transplantation. Case report and review of the literature

Sklarin¹,

Dutcher²,

Wiernik³

1991

American J Hematol

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The success of allogeneic organ transplantation is in great part due to pharmacologic advances in the area of immunosuppressive therapy. However, this achievement has been attained at the price of an unexpectedly high incidence of malignancies in this transplant population. Lymphoid malignancies predominate in this and other immunodeficiency states. There is some controversy in the literature over the clonal or malignant nature of these proliferations. This paper presents a case of Burkitt-like lymphoma occurring after cardiac transplantation. The role of Epstein-Barr virus in the pathogenesis of this disorder is reviewed as are multidisciplinary approaches to its management.

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Effect of cyclosporin‐A (CsA) on the ability of T lymphocyte subsets to inhibit the proliferation of autologous EBV‐transformed B cells

Bejarano

Masucci

Ernberg

et al. 1985

Intl Journal of Cancer

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We have analyzed the effect of Cyclosporin-A (CsA) on the in vitro suppression of Epstein-Barr virus (EBV)-induced B-cell proliferations separated on the basis of cell density. CsA abolished the growth-inhibitory capacity of high-density T cells but influenced only marginally the activity of low-density lymphocytes; this suggested that different mechanisms mediate suppression in the two subsets. Stimulation with irradiated EBV-transformed cells had a different impact on the activity of low- and high-density lymphocytes. Proliferative and cytotoxic responses were inversely correlated, i.e. high-density cells proliferated but exerted low cytotoxicity, while the lytic activity of the low-density subset was stronger in the absence of significant cell proliferation. Proliferation and generation of cytotoxicity were abrogated by CsA in both subsets. The activities could be restored by addition of exogenous IL-2, suggesting that the drug may interfere with the cascade of lymphokine--cell interactions which leads to activation of immune responses. From the analysis of athe CsA effects on the two subsets it seems that the high-density one contains specific memory T cells which are activated and proliferate upon encounter with EBV-infected cells. On the other hand, low-density lymphocytes are induced to release soluble factors with antiproliferative activity. The secretory function was resistant to the suppressive effect of CsA.

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Lymphoma in Cardiac Transplant Recipients Associated with Cyclosporin A, Prednisone and Anti-Thymocyte Globulin (ATG)

Cited by 23 publications

References 10 publications

Epstein-Barr Virus Infections and DNA Hybridization Studies in Posttransplantation Lymphoma and Lymphoproliferative Lesions: The Role of Primary Infection

Epstein-Barr Virus Infections and DNA Hybridization Studies in Posttransplantation Lymphoma and Lymphoproliferative Lesions: The Role of Primary Infection

Lymphomas following cardiac transplantation. Case report and review of the literature

Effect of cyclosporin‐A (CsA) on the ability of T lymphocyte subsets to inhibit the proliferation of autologous EBV‐transformed B cells

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