title: Pre-Emptive Immunotherapy for Clearance of Molecular Disease in Childhood Acute Lymphoblastic Leukemia after Transplantation.
abstract: Monitoring of minimal residual disease (MRD) or chimerism may help guide pre-emptive immunotherapy (IT) with a view to preventing relapse in childhood acute lymphoblastic leukemia (ALL) after transplantation. Patients with ALL who consecutively underwent transplantation in Frankfurt/Main, Germany between January 1, 2005 and July 1, 2014 were included in this retrospective study. Chimerism monitoring was performed in all, and MRD assessment was performed in 58 of 89 patients. IT was guided in 19 of 24 patients with mixed chimerism (MC) and MRD and by MRD only in another 4 patients with complete chimerism (CC). The 3-year probabilities of event-free survival (EFS) were .69 ± .06 for the cohort without IT and .69 ± .10 for IT patients. Incidences of relapse (CIR) and treatment-related mortality (CITRM) were equally distributed between both cohorts (without IT: 3-year CIR, .21 ± .05, 3-year CITRM, .10 ± .04; IT patients: 3-year CIR, .18 ± .09, 3-year CITRM .13 ± .07). Accordingly, 3-year EFS and 3-year CIR were similar in CC and MC patients with IT, whereas MC patients without IT experienced relapse. IT was neither associated with an enhanced immune recovery nor an increased risk for acute graft-versus-host disease. Relapse prevention by IT in patients at risk may lead to the same favorable outcome as found in CC and MRD-negative-patients. This underlines the importance of excellent MRD and chimerism monitoring after transplantation as the basis for IT to improve survival in childhood ALL.
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany. Electronic address: eva.rettinger@kgu.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Rettinger
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Merker
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Emilia
authors.initials: E
authors.lastname: Salzmann-Manrique
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Kreyenberg
authors.affiliation: Pediatric Hematology and Oncology, University of Saarland, Homburg/Saar, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krenn
authors.affiliation: Department of Pediatric Oncology, University of Mannheim, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dürken
authors.affiliation: Department of Pediatric Hematology and Oncology, Children's Hospital of Johannes Gutenberg University, Mainz, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Faber
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Huenecke
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cappel
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bremm
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Willasch
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Bakhtiar
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jarisch
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Soerensen
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.affiliation: University Hospital Frankfurt/Main, Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe-University Frankfurt/Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D005260:Female; D005858:Germany; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy / Q000379:methods* / Q000401:mortality; D017710:Lymphocyte Transfusion; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012008:Recurrence; D055502:Secondary Prevention / Q000379:methods*; D016019:Survival Analysis; D014184:Transplantation, Homologous; D055815:Young Adult
keywords: Allogeneic hematopoietic stem cell transplantation; Chimerism; Minimal residual disease; Pre-emptive immunotherapy