A prospective study on modulation of immunosuppression for Epstein-Barr virus reactivation in pediatric patients who underwent unrelated hematopoietic stem-cell transplantation.
BACKGROUND
Posttransplant lymphoproliferative disease caused by Epstein-Barr virus (EBV-PTLD) is a severe complication after allogeneic hematopoietic stem-cell transplantation (HSCT). We evaluated whether the modulation of immunosuppression (IS) guided by quantitative polymerase chain reaction for EBV (EBV-PCR) was effective as a first-line therapeutic approach for EBV reactivation.


METHODS
Eighty-nine pediatric patients who received an HSCT from an unrelated donor were prospectively assessed by quantitative EBV-PCR. The EBV-PCR threshold to modulate IS was set to more than 300 genomic copies (gc)/10 peripheral blood mononuclear cells.


RESULTS
EBV-PCR positivity was observed in 56 (63%) of 89 patients at a median time of 44 days after HSCT. The variables associated with EBV-PCR positivity were bone marrow stem cells (P=0.047) and a lower total dose of nuclear cells reinfused (P=0.03). Thirty-one patients (35%) had more than or equal to 300 gc. IS was withdrawn or reduced in 18 (58%) and 13 (42%) of the 31 patients, respectively. EBV viral load (EBV-VL) less than 300 gc was achieved in 30 of these 31 patients at a median of 25 days. Only 1 (1%) of the 89 patients progressed to EBV-PTLD. The patients with EBV-VL more than 300 gc had a lower incidence of acute graft versus host disease III-IV than patients with EBV-VL less than 300 gc: 13% vs. 36%, P=0.02. No differences in terms of chronic graft versus host disease, overall survival, event-free survival and transplant-related mortality were observed between the two groups.


CONCLUSIONS
We conclude that PCR-guided modulation of IS may play a role in early intervention for EBV-PTLD and a prospective, randomized study is needed.
Cesaro
Simone
S
Pediatric Hematology Oncology, Department of Pediatrics, University of Padova, Italy. simone.cesaro@ospedaleuniverona.it
Pegoraro
Anna
A
Tridello
Gloria
G
Calore
Elisabetta
E
Pillon
Marta
M
Varotto
Stefania
S
Abate
Davide
D
Barzon
Luisa
L
Mengoli
Carlo
C
Carli
Modesto
M
Messina
Chiara
C
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome
D007166:Immunosuppressive Agents