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 language | English |
|---|---|
| Pages (from-to) | 827-833 |
| Number of pages | 7 |
| Journal | Transplantation |
| Volume | 69 |
| Issue number | 5 |
| Publication status | Published - Mar 15 2000 |
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ASJC Scopus subject areas
- Transplantation
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=17344377301&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17344377301&partnerID=8YFLogxK
M3 - Article
C2 - 10755535
AN - SCOPUS:17344377301
VL - 69
SP - 827
EP - 833
JO - Transplantation
JF - Transplantation
SN - 0041-1337
IS - 5
ER -