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Haematologica. 2016 Mar;101(3):336-45. doi: 10.3324/haematol.2015.134957. Epub 2015 Dec 24.

Minimal residual disease monitoring by 8-color flow cytometry in mantle cell lymphoma: an EU-MCL and LYSA study.

Author information

1
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.
2
Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France.
3
Biological Hematology and Immunology, AP-HP, Groupe Hospitalier Mondor, Créteil, France.
4
Hemato-Oncology, Saint-Louis Hospital, APHP - Paris Diderot - Sorbonne Paris Cité University - INSERM U728 - Institut Universitaire d'Hematologie, France.
5
Département de Médecine, Institut Gustave Roussy, Villejuif, France.
6
Clinical Hematology, University Hospital of Caen, France.
7
Clinical Hematology, Perpignan Hospital, France.
8
Clinical Hematology, INSERM U918, IRIB, Centre Henri Becquerel, Rouen, France.
9
Clinical Hematology, Paris Descartes - Sorbonne Paris Cité University, IMAGINE Institut, Necker Hospital, AP-HP, France.
10
Institute of Medical Informatics, Biometry, and Epidemiology, University of Munich, Germany Department of Internal Medicine III, University Hospital Munich, Germany.
11
Department of Internal Medicine III, University Hospital Munich, Germany.
12
Biological Hematology, Paris Descartes - Sorbonne Paris Cité University, Institut Necker-Enfants Malades, AP-HP, France elizabeth.macintyre@aphp.fr.

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).

PMID:
26703963
PMCID:
PMC4815725
DOI:
10.3324/haematol.2015.134957
[Indexed for MEDLINE]
Free PMC Article

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