INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) typically presents with either polymorphic or monomorphic histology. While both are the end result of immunosuppressive therapies, their origins are felt to be different, resulting in two distinct malignancies with different prognoses and responsiveness to therapy. We attempted to confirm reports suggesting that the relative frequency of these two histologies is shifting over time.
METHODS: 3,040 adult PTLD cases in the United Network for Organ Sharing database from 1999 to 2013 were included. We analyzed changes in PTLD histology over time and used a multivariate logistic regression model to determine factors associated with monomorphic versus polymorphic histology.
RESULTS: We found that the relative proportion of polymorphic vs. monomorphic histology has changed with an increase in the proportion of monomorphic cases with time (1999-2003, 54.9% vs. 45.1%; 2004-2008, 58.3% vs. 41.7%; 2009-2013, 69.7% vs. 30.3%; p<0.001) (see figure). The change in proportion is driven by a gradual increase in the number of monomorphic PTLD cases (1999-2003, 460 cases; 2004-2008, 597 cases; 2009-2013, 821 cases), with a steady number of polymorphic PTLD cases (1999-2003, 378 cases; 2004-2008, 427 cases; 2009-2013, 357 cases), and was most prominent in recipients who were EBV serostatus positive at the time of transplant. Significant changes in the care and outcomes of solid organ transplant patients occurred during this time period, including changes from cyclosporine based immunosuppressive regimens to tacrolimus based regimens and increased survival of allografts and patients. Multivariate logistic regression revealed that tacrolimus use (p=0.034) and increased survival among transplant patients leading to later occurrence of PTLD (p<0.001) were associated with monomorphic PTLD during the time frame analyzed.
CONCLUSION: As the practice of organ transplantation has evolved over time, PTLD has coevolved, shifting from predominately polymorphic to monomorphic histology. These changes in histology have important implications regarding the origin and clinical management of PTLD.
Huntington: Celgene: Consultancy, Other: Travel; Janssen: Consultancy; Pharmacyclics: Honoraria. Schuster: Genentech: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Nordic Nanovector: Consultancy; Merck: Research Funding.
Asterisk with author names denotes non-ASH members.