Relationship between cytomegalovirus (CMV) reactivation, CMV-driven immunity, overall immune recovery and graft-versus-leukaemia effect in children.
The interplay between immune recovery, cytomegalovirus (CMV)-reactivation, CMV-driven immunity and graft-versus-leukaemia effect (GVL) was analysed in 108 children (median age: 8 years) who underwent haematopoietic-stem cell transplantation (HSCT) for acute leukaemia. Follow-up was 2 years unless death or relapse occurred. CMV-polymerase chain reaction (PCR) was programmed weekly until month +3 post-HSCT. Immunomonitoring consisted of sequential lymphocyte subset enumerations and analyses of T-cell proliferative and γ-interferon responses to CMV and to adenovirus. In the 108 recipients, the 2-year relapse rate (RR) was 25% (median time to onset 4·5 months; range: 24 d-17 months). CMV reactivation occurrence was 31% (median time to onset 26 d). Donor/recipient CMV serostatus did not influence RR. Among the 89 recipients disease-free after day +120, i) early CMV-reactivation before day +30 was more frequent (P = 0·01) in the relapse recipient group opposed to the non-relapse group. ii) CD8(+) /CD28(-) and CD4(+) CD45RA(-) T-cell expansions induced by CMV did not influence RR, iii) Recovery of anti-CMV and also anti-adenovirus immunity and of naïve CD4(+) T-cells was faster in the non-relapse group (P = 0·008; 0·009 and 0·002 respectively). In contrast to adult acute myeloid leukaemia, CMV reactivation was associated with increased RR in this paediatric series. Accelerated overall immune recovery rather than CMV-driven immunity had a favourable impact on RR.
Laboratory of Immunology, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), University Paris Diderot, Sorbonne Paris Cité, Paris, France.
Mohamed
M
Jeljeli
Valérie
V
Guérin-El Khourouj
Raphael
R
Porcher
Mony
M
Fahd
Sandrine
S
Leveillé
Karima
K
Yakouben
Marie
M
Ouachée-Chardin
Jerome
J
LeGoff
Debora Jorge
DJ
Cordeiro
Beatrice
B
Pédron
Andre
A
Baruchel
Jean-Hugues
JH
Dalle
Ghislaine
G
Sterkers
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000302:isolation & purification / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology*; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000150:complications / Q000276:immunology* / Q000628:therapy; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome; D014766:Viremia / Q000150:complications / Q000276:immunology; D014775:Virus Activation
children; cytomegalovirus; haematopoietic stem cell transplantation; immune recovery; relapse risk