Targeted monitoring of patients at high risk of post-transplant lymphoproliferative disease by quantitative Epstein-Barr virus polymerase chain reaction.
BACKGROUND
Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disease (PTLD) is a serious complication after allogeneic stem cell transplantation (SCT). The likelihood of PTLD is increased in the presence of specific risk factors. Monitoring of EBV DNA load and early administration of rituximab in patients with high EBV loads is recommended for high-risk patients.


METHODS
Patients at high risk of EBV-associated PTLD were defined as those showing an EBV serological mismatch between donor and recipient, those with lymphoma, those given cord blood grafts, and those with primary EBV disease before SCT. High-risk patients were prospectively monitored by weekly measurement of EBV DNA by quantitative polymerase chain reaction assay, and rituximab was given when the EBV load reached 10,000 copies/mL or symptoms were suggestive of EBV disease. During the study period (July 2005 to the end of June 2007) 131 patients underwent SCT, of whom 53 had high risk factors. A historical control group transplanted between January 2003 to the end of June 2005 was retrospectively used to evaluate the effect of the prospective monitoring strategy.


RESULTS
Of the patients, 30% were positive for EBV DNA at least once; 10% of patients with EBV DNAemia developed PTLD. Risk factors of EBV DNAemia were younger age (P=0.04), receiving transplants from mismatched family or unrelated donors (P=0.01), and acute graft-versus-host disease grades II-IV (P=0.001). The overall frequency of PTLD was 3%; 5.7% in the high-risk group and 1.3% in the standard-risk group. Previous splenectomy (P=0.046) was the only significant risk factor associated with PTLD. In the control group, 6 of 150 patients (4%) developed PTLD; 5/53 (9.4%) in the high-risk group and 1/97 (1%) in the standard-risk group. Human leukocyte antigen-mismatched donors (P<0.01) and EBV-positive donors/EBV-negative recipients (P=0.01) had a significant impact on the risk of PTLD.


CONCLUSIONS
A targeted monitoring strategy among patients at a high risk of EBV-associated PTLD might be helpful to decrease the risk of development of PTLD. However, larger prospective studies are needed to verify this hypothesis.
Omar
H
H
Department of Medicine, Huddinge, Division of Haematology, Karolinska Institutet, Stockholm, Sweden. hamdy.omar@ki.se
Hägglund
H
H
Gustafsson-Jernberg
A
A
LeBlanc
K
K
Mattsson
J
J
Remberger
M
M
Ringdén
O
O
Sparrelid
E
E
Sundin
M
M
Winiarski
J
J
Yun
Z
Z
Ljungman
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood*; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D012307:Risk Factors; D000069283:Rituximab; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D019562:Viral Load / Q000502:physiology; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D004279:DNA, Viral; D007155:Immunologic Factors; D000069283:Rituximab