Risk of lymphoid neoplasia after cardiothoracic transplantation: the influence of underlying disease and human leukocyte antigen type and matching.
BACKGROUND
It has been known for more than 20 years that there is an increased risk of lymphoid neoplasia after cardiothoracic transplantation. Recent studies have demonstrated the importance of primary Epstein-Barr virus (EBV) infection and type of immunosuppressive therapy to the cause of these neoplasms, but the contribution of other factors remains equivocal.


METHODS
The authors followed 1,562 patients undergoing cardiothoracic transplantation at Harefield Hospital, United Kingdom, and used standard cohort methods of analysis to examine whether posttransplant lymphoma risk was related to the underlying disease requiring transplantation or the human leukocyte antigen (HLA) type and matching. Lymphomas were categorized into EBV-associated lymphoproliferative disease (LPD) and EBV-negative non-Hodgkin's lymphoma (NHL), and the authors carried out separate analyses of these.


RESULTS
The authors found no significant association between the underlying disease necessitating transplantation and the risk of lymphoid neoplasia. There was also no evidence of a relation of lymphoma risk with the presence or absence of any particular HLA antigen, although significant protective effects of HLA-B14 and -B57 were found when analyses were conducted without adjustment for multiple testing. Risk of LPD was not associated with degree of HLA mismatching, but there was a significant effect of mismatching on risk of EBV-negative tumors.


CONCLUSIONS
The differential effect of HLA mismatching on the risks of LPD and EBV-negative NHL provides further evidence that these two tumors are distinct etiologic entities. The authors' results suggest that the immunologic cause of EBV-negative NHL may be different from that of LPD. Investigation of the relation of risk of EBV-negative NHL to degree of immunosuppression is needed.
Higgins
Craig D
CD
Section of Epidemiology, Institute of Cancer Research, Brookes Lawley Building, Sutton, Surrey, United Kingdom.
Swerdlow
Anthony J
AJ
Smith
John D
JD
Hunt
Beverley J
BJ
Thomas
J Alero
JA
Burke
Margaret M
MM
Crawford
Dorothy H
DH
Yacoub
Magdi H
MH
D001787:Blood Group Incompatibility / Q000150:complications; D015331:Cohort Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D016027:Heart Transplantation / Q000009:adverse effects*; D006650:Histocompatibility Testing; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008223:Lymphoma / Q000209:etiology*; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000821:virology; D008297:Male; D012307:Risk Factors
D006680:HLA Antigens