title: Peripheral blood late mixed chimerism in leucocyte subpopulations following allogeneic stem cell transplantation for childhood malignancies: does it matter?
abstract: The impact of persistent mixed chimerism (MC) after haematopoietic stem cell transplantation (HSCT) remains unclarified. We investigated the incidence of MC in peripheral blood beyond day +50 after HSCT and its impact on rejection, chronic graft-versus-host disease (c-GvHD) and relapse in 161 children receiving allogeneic HSCT for haematological malignancies. The 1-year incidence of late MC was 26%. Spontaneous conversion to complete donor chimerism (CC) occurred in 43% of patients as compared to 62% after donor lymphocyte infusions. No graft rejection occurred. The 1-year incidence of c-GvHD was 20 ± 7% for MC, and 18 ± 4% for CC patients (P = 0·734). The 3-year cumulative incidence of relapse (CIR) according to chimerism status at days +50 and +100 was 22 ± 4% for CC patients vs. 22 ± 8% for MC patients (day +50; P = 0·935) and 21 ± 4% vs. 20 ± 7% (day +100; P = 0·907). Three-year CIRs in patients with persistent MC and patients with CC/limited MC were comparable (8 ± 7% vs. 19 ± 4%; P = 0·960). HSCT for acute leukaemia or myelodysplastic syndrome as secondary malignancies (hazard ratio (HR) 4·7; P = 0·008), for AML (HR 3·0; P = 0·02) and from mismatched donors (HR 3·1; P = 0·03) were independent factors associated with relapse. Our data suggest that late MC neither protects from c-GvHD nor does it reliably predict impending disease relapse.
authors.affiliation: Department of Paediatrics, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Pichler
authors.affiliation: Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fritsch
authors.affiliation: Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Medical University of Vienna, Vienna, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: König
authors.affiliation: Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Medical University of Vienna, Vienna, Austria.
authors.forename: Helga
authors.initials: H
authors.lastname: Daxberger
authors.affiliation: Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Medical University of Vienna, Vienna, Austria.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Glogova
authors.affiliation: Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.affiliation: Department of Paediatrics, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Breuer
authors.affiliation: Department of Paediatrics, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Anita
authors.initials: A
authors.lastname: Lawitschka
authors.affiliation: Department of Paediatrics, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Ece D
authors.initials: ED
authors.lastname: Güclü
authors.affiliation: Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Medical University of Vienna, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Karlhuber
authors.affiliation: Department of Paediatrics, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holter
authors.affiliation: Department of Paediatrics, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.|Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Medical University of Vienna, Vienna, Austria.
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.affiliation: Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lion
authors.affiliation: Department of Paediatrics, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Matthes-Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection; D006086:Graft vs Host Disease; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D016131:Lymphocyte Subsets; D008297:Male; D016609:Neoplasms, Second Primary; D012008:Recurrence; D013997:Time Factors; D018183:Transplantation Chimera / Q000097:blood*; D019172:Transplantation Conditioning / Q000379:methods; D055815:Young Adult
keywords: allogeneic stem cell transplantation; childhood malignancies; chimerism analysis; chronic GvHD; relapse