title: Minimal residual disease monitoring by 8-color flow cytometry in mantle cell lymphoma: an EU-MCL and LYSA study.
abstract: Quantification of minimal residual disease may guide therapeutic strategies in mantle cell lymphoma. While multiparameter flow cytometry is used for diagnosis, the gold standard method for minimal residual disease analysis is real-time quantitative polymerase chain reaction (RQ-PCR). In this European Mantle Cell Lymphoma network (EU-MCL) pilot study, we compared flow cytometry with RQ-PCR for minimal residual disease detection. Of 113 patients with at least one minimal residual disease sample, RQ-PCR was applicable in 97 (86%). A total of 284 minimal residual disease samples from 61 patients were analyzed in parallel by flow cytometry and RQ-PCR. A single, 8-color, 10-antibody flow cytometry tube allowed specific minimal residual disease assessment in all patients, with a robust sensitivity of 0.01%. Using this cut-off level, the true-positive-rate of flow cytometry with respect to RQ-PCR was 80%, whereas the true-negative-rate was 92%. As expected, RQ-PCR frequently detected positivity below this 0.01% threshold, which is insufficiently sensitive for prognostic evaluation and would ideally be replaced with robust quantification down to a 0.001% (10-5) threshold. In 10 relapsing patients, the transition from negative to positive by RQ-PCR (median 22.5 months before relapse) nearly always preceded transition by flow cytometry (4.5 months), but transition to RQ-PCR positivity above 0.01% (5 months) was simultaneous. Pre-emptive rituximab treatment of 2 patients at minimal residual disease relapse allowed re-establishment of molecular and phenotypic complete remission. Flow cytometry minimal residual disease is a complementary approach to RQ-PCR and a promising tool in individual mantle cell lymphoma therapeutic management. (clinicaltrials identifiers: 00209209 and 00209222).
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France Clinical Hematology, Paris Descartes - Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Cheminant
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Derrieux
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Touzart
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Schmit
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Grenier
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Trinquand
authors.affiliation: Biological Hematology and Immunology, AP-HP, Groupe Hospitalier Mondor, Créteil, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Delfau-Larue
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lhermitte
authors.affiliation: Hemato-Oncology, Saint-Louis Hospital, APHP - Paris Diderot - Sorbonne Paris Cité University - INSERM U728 - Institut Universitaire d'Hematologie, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
authors.affiliation: Département de Médecine, Institut Gustave Roussy, Villejuif, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.affiliation: Clinical Hematology, University Hospital of Caen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cheze
authors.affiliation: Clinical Hematology, Perpignan Hospital, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Sanhes
authors.affiliation: Clinical Hematology, INSERM U918, IRIB, Centre Henri Becquerel, Rouen, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
authors.affiliation: Clinical Hematology, Paris Descartes - Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France.
authors.forename: François
authors.initials: F
authors.lastname: Lefrère
authors.affiliation: Clinical Hematology, Paris Descartes - Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.affiliation: Institute of Medical Informatics, Biometry, and Epidemiology, University of Munich, Germany Department of Internal Medicine III, University Hospital Munich, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hoster
authors.affiliation: Department of Internal Medicine III, University Hospital Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France.
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.affiliation: Clinical Hematology, Paris Descartes - Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France elizabeth.macintyre@aphp.fr.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010865:Pilot Projects; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor