Adenoviral infections after transplantation of positive selected stem cells from haploidentical donors in children: an update.
We present updated results of stem cell transplantation with highly purified stem cells from haploidentical parental donors and infection with human adenovirus (HAdV) post stem cell transplantation (SCT). Survival post SCT is primarily determined by relapse, infections and far less by GvHD or other transplant related mortality. During the immune reconstitution the host is at significant risk for severe viral infections. HAdV infection is especially in children an important complication post SCT, with significant morbidity and mortality despite new antiviral treatment strategies. Although control of infection seems to require T-cells, the characterization of HAdV-specific T-cells post SCT has not been introduced in surveillance and treatment decisions.


METHODS
Therefore we evaluated the impact of HAdV-infections on the survival between 1995 and 2004 (n = 63) and studied the occurrence of adenovirus-specific T-cells in children with (n = 9) and without (n = 9) HAdV-infection post allogeneic SCT and in healthy donors (n = 53). After stimulation ex-vivo with HAdV-antigen IFN-gamma secreting T-cells were analyzed by flowcytometry and defined as HAdV-specific T-cells.


RESULTS
Until day 180 post SCT the cumulative incidence of all lethal viral infections (HAdV n = 5, cytomegalovirus n = 3, herpes simplex virus n = 1) was 16 % for the whole cohort of patients. Cumulative incidence of HAdV-associated mortality was 8.5 %. Cumulative incidence of all lethal viral infections could be now reduced from 16 % to 8 % in conjunction with new surveillance- and therapeutic-strategies. Children with HAdV-associated mortality all had no specific T-cells, although reconstitution of absolute lymphocyte counts exceeded 300/microl within 30 days post transplant. Patients who cleared HAdV infection had normal frequencies of HAdV-specific T-cells until day 200 post SCT.


CONCLUSIONS
In summary adenovirus specific T-cell reconstitution should be monitored in patients after SCT to limit the use of anti viral chemotherapy and help to identify those patients that would benefit from new therapeutic strategies like adoptive transfer of virus specific T-cells.
Feuchtinger
T
T
Department of Pediatric Hematology/Oncology, University Children's Hospital, Eberhard-Karls-University, Tübingen, Germany.
Richard
C
C
Pfeiffer
M
M
Neuhäuser
F
F
Lücke
J
J
Handgretinger
R
R
Greil
J
J
Bader
P
P
Klingebiel
T
T
Schlegel
P-G
PG
Jahn
G
G
Niethammer
D
D
Lang
P
P
D000258:Adenovirus Infections, Human / Q000276:immunology* / Q000401:mortality; D000260:Adenoviruses, Human / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008223:Lymphoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D009894:Opportunistic Infections / Q000276:immunology* / Q000401:mortality; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology