title: Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage.
abstract: 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) datafile. 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.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Crane
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Powell
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.|Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Rumen
authors.initials: R
authors.lastname: Kostadinov
authors.affiliation: Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, MD, USA.
authors.forename: Patrick Tim
authors.initials: PT
authors.lastname: Rocafort
authors.affiliation: Veterans' Affairs Healthcare System and Division of Nephrology, Department of Medicine, University of California-San Diego, San Diego, CA, USA.
authors.forename: Dena E
authors.initials: DE
authors.lastname: Rifkin
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burger
authors.affiliation: Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
authors.affiliation: Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Lode J
authors.initials: LJ
authors.lastname: Swinnen
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Duffield
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000473:pathology; D065095:Calcineurin Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D002490:Central Nervous System / Q000473:pathology*; D016208:Databases, Factual; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects; D008223:Lymphoma / Q000209:etiology / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016017:Odds Ratio; D016377:Organ Transplantation / Q000009:adverse effects; D011183:Postoperative Complications; D012044:Regression Analysis; D012189:Retrospective Studies
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: Epstein-Barr virus; calcineurin inhibitors; mycophenolate mofetil; post-transplant lymphoproliferative disorder; primary central nervous system lymphoma