Reduced incidence of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder using preemptive antiviral therapy.
BACKGROUND
Posttransplant lymphoproliferative disorder (PTLD) has been observed with increasing frequency consequent to the availability of more effective and potent immunosuppression. Prior work suggested that a peripheral blood monitoring strategy detecting peripheral B lymphoproliferation was effective in the early diagnosis of PTLD among 7 of 179 (3.9%) consecutive transplant recipients. Each of those seven patients received at least one course of antithymocyte globulin, Minnesota antilymphocyte globulin, or OKT3 before developing PTLD.


METHODS
To determine whether antiviral prophylaxis might reduce the incidence of PTLD, a subsequent group of 198 consecutive recipients received either ganciclovir or acyclovir during antilymphocyte antibody administration. When the donor or recipient were cytomegalovirus-seropositive, ganciclovir was given; acyclovir was used when both were cytomegalovirus-seronegative. Baseline and protocol posttransplant cell surface profiles were obtained using immunofluorescence and flow cytometry to detect T cells, lymphocyte activation markers, and the CD19 B cell antigen.


RESULTS
Demographic factors, including the incidence of recipients more than 50 years of age, non-Caucasians, previous transplantation, and diabetes mellitus, were similar in both groups. Additionally, the number of patients receiving antilymphocyte preparations was similar. However, only one patient (0.5%) from the latter group who received preemptive antiviral therapy developed PTLD. Although elevations in CD19+ B cells preceded clinical PTLD among each of the seven earlier patients, evidence of peripheral B cell proliferation was not demonstrated for the sole patient from the latter group, which suggests a possible effect of antiviral therapy.


CONCLUSIONS
Prophylactic antiviral therapy may reduce the sensitivity of peripheral monitoring for B lymphoproliferation, but the dramatic reduction in PTLD incidence strongly supports its use among transplant recipients at risk.
Darenkov
I A
IA
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA.
Marcarelli
M A
MA
Basadonna
G P
GP
Friedman
A L
AL
Lorber
K M
KM
Howe
J G
JG
Crouch
J
J
Bia
M J
MJ
Kliger
A S
AS
Lorber
M I
MI
D000212:Acyclovir / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018941:Antigens, CD19 / Q000032:analysis; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D015774:Ganciclovir / Q000627:therapeutic use*; D004854:Herpesvirus 4, Human; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008232:Lymphoproliferative Disorders / Q000453:epidemiology* / Q000517:prevention & control / Q000821:virology; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D016035:Pancreas Transplantation; D011183:Postoperative Complications / Q000517:prevention & control*; D012189:Retrospective Studies
D015703:Antigens, CD; D018941:Antigens, CD19; D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D015774:Ganciclovir; D000212:Acyclovir