title: Early recipient chimerism testing in the T- and NK-cell lineages for risk assessment of graft rejection in pediatric patients undergoing allogeneic stem cell transplantation.
abstract: Timely diagnosis of impending graft rejection is crucial for effective therapeutic intervention after allogeneic hematopoietic stem cell transplantation (SCT). We have investigated the predictive potential of early leukocyte subset-specific chimerism for graft loss in children undergoing SCT. In total, 192 pediatric patients transplanted for the treatment of malignant and non-malignant diseases after reduced-intensity or myeloablative conditioning were investigated. Surveillance of lineage-specific chimerism was initiated upon first appearance of leukocyte counts amenable to cell sorting. Graft rejection occurred in 23 patients between 24 and 492 days post-transplant (median 63 days). The first chimerism analysis of T and NK cells performed at a median of 20 days after SCT identified three different risk groups that were independent from the conditioning regimen: recipient chimerism (RC) levels in T cells below 50% indicated a very low risk of rejection (1.4%), whereas high levels of RC (>90%) both in T and NK cells heralded graft loss in the majority of patients (90%) despite therapeutic interventions. RC >50% in T cells and ≤90% in NK cells defined an intermediate-risk group in which timely immunotherapy frequently prevented rejection. Early assessment of T- and NK-cell chimerism can therefore be instrumental in the risk assessment and therapeutic management of imminent graft rejection.
authors.affiliation: St Anna Children's Hospital, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Breuer
authors.forename: S
authors.initials: S
authors.lastname: Preuner
authors.forename: G
authors.initials: G
authors.lastname: Fritsch
authors.forename: H
authors.initials: H
authors.lastname: Daxberger
authors.forename: M
authors.initials: M
authors.lastname: Koenig
authors.forename: U
authors.initials: U
authors.lastname: Poetschger
authors.forename: A
authors.initials: A
authors.lastname: Lawitschka
authors.forename: C
authors.initials: C
authors.lastname: Peters
authors.forename: G
authors.initials: G
authors.lastname: Mann
authors.forename: T
authors.initials: T
authors.lastname: Lion
authors.forename: S
authors.initials: S
authors.lastname: Matthes-Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D006084:Graft Rejection / Q000175:diagnosis* / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007694:Killer Cells, Natural / Q000378:metabolism*; D008212:Lymphocyte Depletion; D022423:Myeloid Cells / Q000378:metabolism; D011379:Prognosis; D018570:Risk Assessment; D013601:T-Lymphocytes / Q000378:metabolism*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult