Reversibility of Lymphomas and Lymphoproliferative Lesions Developing Under Cyclosporin-Steroid Therapy

Starzl, Thomas E.; Porter, Kenneth Wiggins; Iwatsuki, Shunzaburo; Rosenthal, J. Thomas; Shaw, Byers W.; Atchison, Robert W.; Nalesnik, M; Ho, Monto; Griffith, Bartley P.; Hakala, Thomas R.; Hardesty, Robert L.; Jaffe, Ronald; Bahnson, Henry T.

doi:10.1016/s0140-6736(84)90994-2

Cited by 1,156 publications

(478 citation statements)

References 18 publications

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“…In these 2 patients, the lymphomas spontaneously regressed after withdrawal of MTX therapy (1). The spontaneous disappearance of the lymphomatous process in these 2 patients was similar to the regression of lymphoproliferative disorders seen upon withdrawal of cyclosporine therapy in transplantation patients (2).…”

supporting

confidence: 60%

“…Patients treated with immunosuppressive agents after organ transplantation are at risk for the development of PTLD (2). The majority of PTLDs have a B cell phenotype: only rare T cell proliferations have been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Three lines of evidence support a causative role for EBV in the etiology of B cell PTLD. First, withdrawal of immunosuppressive therapy can lead to a spontaneous regression of the PTLD (2). It is thought that the restoration of the immune system leads to an eradication of EBV-positive lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

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Epstein‐Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis

Rijn

Cleary

Variakojis

et al. 1996

Arthritis & Rheumatism

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Objective. A causative role for Epstein-Barr virus (EBV) in the development of lymphoma in patients with rheumatoid arthritis (RA) has been proposed. We investigated the molecular features of EBV-positive diffuse large cell lymphomas in 2 patients with RA.Methods. Southern blot analysis for immunoglobulin gene rearrangements, terminal repeat analysis for clonality of the EBV genome, and double-labeling of the lymphoma cells by in situ hybridization and immunoperoxidase staining were performed.Results. In both cases, double-labeling studies localized the EBV genome to the malignant B cells. Both neoplasms contained clonal immunoglobulin gene rearrangements and clonal EBV genomes.Conclusion. Our data indicate that EBV infection was an early step in the development of these neoplasms. The findings further extend knowledge on the similarity of this subset of lymphomas to posttransplantation lymphomas and emphasize the role of immunosuppression in their genesis.Previous studies have shown that a subset of lymphomas in patients with rheumatic disease share features with Epstein-Ban-virus (EBVtpositive posttransplant lymphoproliferative disorders (PTLD). Initially, we reported 2 cases of EBV-associated lymphoma in patients who received methotrexate (MTX)

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supporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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Epstein‐Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis

Rijn

Cleary

Variakojis

et al. 1996

Arthritis & Rheumatism

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“…2 This could be ascribed to (1) a better knowledge and handling of immunosuppressive drugs, (2) a preliminary use of FK506 by Starzl et al 24 ; and (3) a population consisting of adult patients. 25 Indeed a high incidence of LPD has been reported in children treated with FK506.…”

Section: Gammopathies In Fk506-or Csa-treated Patientsmentioning

confidence: 99%

Occurrence of gammopathies and lymphoproliferative disorders in liver transplant recipients randomized to tacrolimus (FK506)- or cyclosporine-based immunosuppression

et al. 1998

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Lymphoproliferative disorders (LPDs) are a serious side effect of immunosuppression after liver transplantation, and the introduction on the market of a new immunosuppressive drug has been associated with an increased risk of these disorders. To compare the effect of cyclosporine A (CSA) and FK506 in a clinical setting, the incidence of monoclonal or oligoclonal gammopathies known to often precede the appearance of LPDs was evaluated. A total of 88 adult patients was analyzed, 46 were prospectively randomized to CSA and 42 to FK506 for immunosuppression. None of these patients had gammopathy before transplantation. All the patients were tested for immunoglobulin abnormalities five to nine times during a period of 1 year and then two to four times per year thereafter from December 1990 until March 1997. The same incidence of serum immunoglobulin (Ig) abnormalities was observed in both groups (13%) with a mean delay of appearance of 11.1 ؎ 5.9 versus 7.6 ؎ 3.6 months for CSA and FK506, respectively (P G .05). In each group, the gammopathies were transient in 3 patients and persisted in 2. The class of Ig involved was IgG, and a monoclonal component was documented in 2 patients treated with CSA and in 3 patients with FK506. One patient treated with FK506 developed an LPD localized to the lymph nodes 8 months after the occurrence of serum protein abnormalities. The lymphoproliferative lesions subsequently disappeared with the reduction of immunosuppression. In this study, an immunosuppressive regimen of FK506 has not shown an increased incidence of lymphoproliferation compared with CSA in adult liver transplant patients.

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“…8,19,20 EBV-associated PTLD appears to be most effectively treated by tapering of the doses of the immunosuppressive drugs used to prevent transplant organ rejection. 17,21 Because different viruses can give rise to similar organ pathologies, [22][23][24][25][26][27][28][29] selection of the appropriate therapeutic approach involves accurate diagnosis of disease etiology.…”

mentioning

confidence: 99%

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

Bai

Rogers

Harkins

et al. 2000

The Journal of Molecular Diagnostics

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Human herpesviruses can cause significant morbidity and mortality in pediatric solid organ transplant recipients. It was hypothesized that viral burden quantification by polymerase chain reaction using an internal calibration standard could aid in distinguishing between viral disease and latency. Here we report the results of a 2-year prospective study of 27 pediatric solid organ (liver, kidney, or heart) transplant recipients in which multiple samples were analyzed for levels of all eight human herpesviruses by internal calibration standard-polymerase chain reaction. Herpes simplex viruses 1 and 2, varicella-zoster virus, and Kaposi's sarcoma-associated herpesvirus were not detected in any of these samples. Human herpesvirus types 6 and 7 were detected in half of the patients, but were present at low levels, similar to those found in reference populations. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were detected in 89% and 56% of the patients, respectively. Viral burden analysis suggested distinct patient populations for CMV, with a natural cutoff of 10,000 viral targets/ml blood strongly associated with disease. In some cases, a dramatic increase in CMV levels preceded clinical evidence of disease by several weeks. EBV viral burden was relatively high in the only patient presenting with an EBV syndrome. However, two other patients without evidence of EBV disease had single samples with high EBV burden. Rapid reduction in both EBV and CMV burden occurred with antiviral treatment. These data suggest that viral burden analysis using internal calibration standard-polymerase chain reaction for CMV, and possibly other herpesviruses, is an effective method for monitoring pediatric transplant patients for significant herpesvirus infection and response to therapy.

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Reversibility of Lymphomas and Lymphoproliferative Lesions Developing Under Cyclosporin-Steroid Therapy

Cited by 1,156 publications

References 18 publications

Epstein‐Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis

Epstein‐Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis

Occurrence of gammopathies and lymphoproliferative disorders in liver transplant recipients randomized to tacrolimus (FK506)- or cyclosporine-based immunosuppression

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

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