title: Minimal residual disease after allogeneic stem cell transplant: a comparison among multiparametric flow cytometry, Wilms tumor 1 expression and chimerism status (Complete chimerism versus Low Level Mixed Chimerism) in acute leukemia.
abstract: Relapse represents the main cause of treatment failure after allogeneic stem cell transplant (allo-SCT). The detection of minimal residual disease (MRD) by multiparametric flow cytometry (MFC), chimerism, cytogenetics and molecular analysis may be critical to prevent relapse. Therefore, we assessed the overall agreement among chimerism (low level mixed chimerism [LL-MC] vs. complete chimerism [CC]), MFC and Wilms tumor 1 (WT1) mRNA to detect MRD and investigated the impact of MRD obtained from the three methods on patient outcome. Sixty-seven fresh bone marrow (BM) samples from 24 patients (17 acute myeloid leukemia [AML], seven acute lymphoblastic leukemia [ALL]) in complete remission (CR) after allo-SCT were investigated at different time points. A moderate agreement was found among the three techniques investigated. A higher concordance between positive results from MFC (75.0% vs. 32.7%, p = 0.010) and WT1 (58.3% vs. 29.1%, p = 0.090) was detected among LL-MC rather than CC samples. Relapse-free survival (RFS) and overall survival (OS) were found to be higher in MRD negative patients than in MRD positive patients analyzed with MFC and WT1. Our results discourage the use of low autologous signals as the only marker of MRD, and suggest the usefulness of MFC and WT1 real-time quantitative polymerase chain reaction (RQ-PCR) in stratifying patients with respect to risk of relapse.
authors.affiliation: Department of Hematology and Stem Cell Transplantation Unit.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rossi
authors.forename: Angelo Michele
authors.initials: AM
authors.lastname: Carella
authors.forename: Maria Marta
authors.initials: MM
authors.lastname: Minervini
authors.forename: Lucia
authors.initials: L
authors.lastname: Savino
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Michele Mario
authors.initials: MM
authors.lastname: Greco
authors.forename: Emanuela
authors.initials: E
authors.lastname: Merla
authors.forename: Gianni
authors.initials: G
authors.lastname: Quarta
authors.forename: Giacomo
authors.initials: G
authors.lastname: Loseto
authors.forename: Silvana
authors.initials: S
authors.lastname: Capalbo
authors.forename: Gaetano
authors.initials: G
authors.lastname: Palumbo
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascavilla
mesh_terms: D000293:Adolescent; D000328:Adult; D046528:Chimerism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012680:Sensitivity and Specificity; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015514:Oncogene Proteins, Fusion