TY - JOUR
T1 - Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage
AU - Crane, Genevieve M.
AU - Powell, Helen
AU - Kostadinov, Rumen
AU - Rocafort, Patrick Tim
AU - Rifkin, Dena E.
AU - Burger, Peter C.
AU - Ambinder, Richard F.
AU - Swinnen, Lode J.
AU - Borowitz, Michael J.
AU - Duffield, Amy S.
PY - 2015
Y1 - 2015
N2 - Immunosuppression for solid organ transplantation increases lymphoproliferative disease risk. While central nervous system (CNS) involvement is more rare, we noticed an increase in primary CNS (PCNS) disease. To investigate a potential association with the immunosuppressive regimen we identified all post-transplant lymphoproliferative disease (PTLD) cases diagnosed over a 28-year period at our institution (174 total, 29 PCNS) and all similar cases recorded in a United Network for Organ Sharing-Organ Procurement and Transplant Network (UNOS-OPTN) data file. While no PCNS cases were diagnosed at our institution between 1986 and 1997, they comprised 37% of PTLD cases diagnosed from 2011-2014. PCNS disease was more often associated with renal vs. other organ transplant, Epstein-Barr virus, large B-cell morphology and mycophenolate mofetil (MMF) as compared to PTLD that did not involve the CNS. Calcineurin inhibitors were protective against PCNS disease when given alone or in combination with MMF. A multivariate analysis of a larger UNOS-OPTN dataset confirmed these findings, where both MMF and lack of calcineurin inhibitor usage were independently associated with risk for development of PCNS PTLD. These findings have significant implications for the transplant community, particularly given the introduction of new regimens lacking calcineurin inhibitors. Further investigation into these associations is warranted.
AB - Immunosuppression for solid organ transplantation increases lymphoproliferative disease risk. While central nervous system (CNS) involvement is more rare, we noticed an increase in primary CNS (PCNS) disease. To investigate a potential association with the immunosuppressive regimen we identified all post-transplant lymphoproliferative disease (PTLD) cases diagnosed over a 28-year period at our institution (174 total, 29 PCNS) and all similar cases recorded in a United Network for Organ Sharing-Organ Procurement and Transplant Network (UNOS-OPTN) data file. While no PCNS cases were diagnosed at our institution between 1986 and 1997, they comprised 37% of PTLD cases diagnosed from 2011-2014. PCNS disease was more often associated with renal vs. other organ transplant, Epstein-Barr virus, large B-cell morphology and mycophenolate mofetil (MMF) as compared to PTLD that did not involve the CNS. Calcineurin inhibitors were protective against PCNS disease when given alone or in combination with MMF. A multivariate analysis of a larger UNOS-OPTN dataset confirmed these findings, where both MMF and lack of calcineurin inhibitor usage were independently associated with risk for development of PCNS PTLD. These findings have significant implications for the transplant community, particularly given the introduction of new regimens lacking calcineurin inhibitors. Further investigation into these associations is warranted.
KW - Calcineurin inhibitors
KW - Epstein-Barr virus
KW - Mycophenolate mofetil
KW - Post-transplant lymphoproliferative disorder
KW - Primary central nervous system lymphoma
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U2 - 10.18632/oncotarget.5292
DO - 10.18632/oncotarget.5292
M3 - Article
C2 - 26460822
AN - SCOPUS:84946042329
SN - 1949-2553
VL - 6
SP - 33849
EP - 33866
JO - Oncotarget
JF - Oncotarget
IS - 32
ER -