Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney, and liver transplant

Gianpietro Dotti, Roberto Fiocchi, Teresio Motta, Amando Gamba, Eliana Gotti, Bruno Gridelli, Gianmaria Borleri, Cristina Manzoni, Piera Viero, Giuseppe Remuzzi, Tiziano Barbui, Alessandro Rambaldi

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Abstract

Background. Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. Methods. We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. Results. All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. Conclusions. Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.

Original languageEnglish
Pages (from-to)827-833
Number of pages7
JournalTransplantation
Volume69
Issue number5
Publication statusPublished - Mar 15 2000

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Lymphoproliferative Disorders
Human Herpesvirus 4
Survivors
Transplants
Kidney
Liver
Lymphoma
Genome
Immunosuppression
myc Genes
Gene Rearrangement
Southern Blotting
Drug Therapy
Polymerase Chain Reaction
Survival
Mortality

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Dotti, G., Fiocchi, R., Motta, T., Gamba, A., Gotti, E., Gridelli, B., ... Rambaldi, A. (2000). Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney, and liver transplant. Transplantation, 69(5), 827-833.

Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney, and liver transplant. / Dotti, Gianpietro; Fiocchi, Roberto; Motta, Teresio; Gamba, Amando; Gotti, Eliana; Gridelli, Bruno; Borleri, Gianmaria; Manzoni, Cristina; Viero, Piera; Remuzzi, Giuseppe; Barbui, Tiziano; Rambaldi, Alessandro.

In: Transplantation, Vol. 69, No. 5, 15.03.2000, p. 827-833.

Research output: Contribution to journalArticle

Dotti, G, Fiocchi, R, Motta, T, Gamba, A, Gotti, E, Gridelli, B, Borleri, G, Manzoni, C, Viero, P, Remuzzi, G, Barbui, T & Rambaldi, A 2000, 'Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney, and liver transplant', Transplantation, vol. 69, no. 5, pp. 827-833.
Dotti G, Fiocchi R, Motta T, Gamba A, Gotti E, Gridelli B et al. Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney, and liver transplant. Transplantation. 2000 Mar 15;69(5):827-833.
Dotti, Gianpietro ; Fiocchi, Roberto ; Motta, Teresio ; Gamba, Amando ; Gotti, Eliana ; Gridelli, Bruno ; Borleri, Gianmaria ; Manzoni, Cristina ; Viero, Piera ; Remuzzi, Giuseppe ; Barbui, Tiziano ; Rambaldi, Alessandro. / Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney, and liver transplant. In: Transplantation. 2000 ; Vol. 69, No. 5. pp. 827-833.
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abstract = "Background. Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. Methods. We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. Results. All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44{\%} of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31{\%}). A c-myc gene rearrangement was found in two cases (13{\%}), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. Conclusions. Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.",
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T1 - Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney, and liver transplant

AU - Dotti, Gianpietro

AU - Fiocchi, Roberto

AU - Motta, Teresio

AU - Gamba, Amando

AU - Gotti, Eliana

AU - Gridelli, Bruno

AU - Borleri, Gianmaria

AU - Manzoni, Cristina

AU - Viero, Piera

AU - Remuzzi, Giuseppe

AU - Barbui, Tiziano

AU - Rambaldi, Alessandro

PY - 2000/3/15

Y1 - 2000/3/15

N2 - Background. Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. Methods. We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. Results. All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. Conclusions. Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.

AB - Background. Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. Methods. We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. Results. All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. Conclusions. Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.

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