Research Papers:

Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage

Genevieve M. Crane, Helen Powell, Rumen Kostadinov, Patrick Tim Rocafort, Dena E. Rifkin, Peter C. Burger, Richard F. Ambinder, Lode J. Swinnen, Michael J. Borowitz and Amy S. Duffield _

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Oncotarget. 2015; 6:33849-33866. https://doi.org/10.18632/oncotarget.5292

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Genevieve M. Crane1, Helen Powell2, Rumen Kostadinov2,3, Patrick Tim Rocafort4, Dena E. Rifkin5, Peter C. Burger1, Richard F. Ambinder3, Lode J. Swinnen3, Michael J. Borowitz1, Amy S. Duffield1

1Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

2Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

3Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Baltimore, MD, USA

4Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, MD, USA

5Veterans’ Affairs Healthcare System and Division of Nephrology, Department of Medicine, University of California-San Diego, San Diego, CA, USA

Correspondence to:

Amy S. Duffield, e-mail: [email protected]

Keywords: post-transplant lymphoproliferative disorder, primary central nervous system lymphoma, Epstein-Barr virus, mycophenolate mofetil, calcineurin inhibitors

Received: August 03, 2015     Accepted: September 04, 2015     Published: September 16, 2015


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.

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