title: Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for adult acute lymphoblastic leukemia.
abstract: Little data are available on the relative merits of chimerism and minimal residual disease (MRD) monitoring for relapse prediction after allogeneic hematopoietic stem cell transplantation (HCT). We performed a retrospective analysis of serial chimerism assessments in 101 adult HCT recipients with acute lymphoblastic leukemia (ALL) and of serial MRD assessments in a subgroup of 22 patients. All patients had received myeloablative conditioning. The cumulative incidence of relapse was significantly higher in the patients with increasing mixed chimerism (in-MC) compared with those with complete chimerism, low-level MC, and decreasing MC, but the sensitivity of in-MC detection with regard to relapse prediction was only modest. In contrast, MRD assessment was highly sensitive and specific. Patients with MRD positivity after HCT had the highest incidence of relapse among all prognostic groups analyzed. The median time from MRD positivity to relapse was longer than the median time from detection of in-MC, but in some cases in-MC preceded MRD positivity. We conclude that MRD assessment is a powerful prognostic tool that should be included in the routine post-transplantation monitoring of patients with ALL, but chimerism analysis may provide additional information in some cases. Integration of these tools and clinical judgment should allow optimal decision making with regard to post-transplantation therapeutic interventions.
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Berlin, Germany. Electronic address: theis.terwey@charite.de.
authors.forename: Theis Helge
authors.initials: TH
authors.lastname: Terwey
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Philipp Georg
authors.initials: PG
authors.lastname: Hemmati
authors.affiliation: Institute of Legal Medicine and Forensic Sciences, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Nagy
authors.affiliation: Department of Medicine II, Goethe University Hospital, Frankfurt, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Pfeifer
authors.affiliation: Department of Medicine II, Goethe University Hospital, Frankfurt, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.affiliation: Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Brüggemann
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Tanja Melinh
authors.initials: TM
authors.lastname: Le Duc
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.affiliation: Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Arnold
mesh_terms: D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D019653:Myeloablative Agonists
keywords: Acute lymphoblastic leukemia; Chimerism; Minimal residual disease; Relapse; Stem cell transplantation