Increased incidence of EBV-related disease following paediatric stem cell transplantation with reduced-intensity conditioning.
The incidence of Epstein-Barr virus (EBV) viraemia and lymphoproliferative disease (LPD) was studied in a consecutive cohort of 128 paediatric patients undergoing stem cell transplantation (SCT) with reduced-intensity conditioning (RIC; n = 65) or conventional-intensity conditioning (CIC; n = 68). Following CIC, six of 68 (8%) developed viraemia; all remained asymptomatic. EBV viraemia (23 of 65 patients = 35%, P < 0.001) and LPD (10 of 65 = 15%, P < 0.001) were significantly more frequent following RIC. Of the 23 RIC patients who developed viraemia, eight remained asymptomatic, five had symptomatic viraemia (fever +/- rash), and 10 patients developed LPD, two of whom died. An absolute lymphocyte count of <0.3 x 10(9)/l at the time of onset of viraemia was strongly predictive of development of LPD (P < 0.05) in this group. The incidence of viraemia was significantly higher in patients receiving serotherapy with antithymocyte globulin (ATG; 15 of 43, 35%) than Campath (12 of 73, 16.4%, P < 0.05). Primary immunodeficiency and acute graft-versus-host disease were associated with EBV viraemia in univariate analysis, but were not independent risk factors. In conclusion, EBV viraemia and LPD appear to be significantly more common in children following RIC SCT, particularly with selective depletion of recipient T cells relative to B cells following the use of ATG. This probably reflects the profound immunosuppression following RIC SCT, together with the incomplete ablation of recipient-derived B cells.
Cohen
Jonathan
J
Department of Bone Marrow Transplantation, Great Ormond Street Hospital NHS Trust, London, UK.
Gandhi
Minal
M
Naik
Paru
P
Cubitt
David
D
Rao
Kanchan
K
Thaker
Urvashi
U
Davies
E Graham
EG
Gaspar
H Bobby
HB
Amrolia
Persis J
PJ
Veys
Paul
P
D000293:Adolescent; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000821:virology; D004854:Herpesvirus 4, Human; D006801:Humans; D007116:Immunization, Passive; D015994:Incidence; D007223:Infant; D018655:Lymphocyte Count; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000601:surgery* / Q000821:virology; D008297:Male; D015999:Multivariate Analysis; D012307:Risk Factors; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D000074323:Alemtuzumab