A probabilistic approach for the evaluation of minimal residual disease by multiparameter flow cytometry in leukemic B-cell chronic lymphoproliferative disorders

Multiparameter flow cytometry has become an essential tool for monitoring response to therapy in hematological malignancies, including B-cell chronic lymphoproliferative disorders (B-CLPD). However, depending on the expertise of the operator minimal residual disease (MRD) can be misidentified, given that data analysis is based on the definition of expert-based bidimensional plots, where an operator selects the subpopulations of interest. Here, we propose and evaluate a probabilistic approach based on pattern classification tools and the Bayes theorem, for automated analysis of flow cytometry data from a group of 50 B-CLPD versus normal peripheral blood B-cells under MRD conditions, with the aim of reducing operator-associated subjectivity. The proposed approach provided a tool for MRD detection in B-CLPD by flow cytometry with a sensitivity of ≤8 × 10-5 (median of ≤2 × 10-7). Furthermore, in 86% of B-CLPD cases tested, no events corresponding to normal B-cells were wrongly identified as belonging to the neoplastic B-cell population at a level of ≤10-7. Thus, this approach based on the search for minimal numbers of neoplastic B-cells similar to those detected at diagnosis could potentially be applied with both a high sensitivity and specificity to investigate for the presence of MRD in virtually all B-CLPD. Further studies evaluating its efficiency in larger series of patients, where reactive conditions and non-neoplastic disorders are also included, are required to confirm these results. © 2008 International Society for Advancement of Cytometry.European Commission (EuroFlow); Grant number: LSHB-CT-2006- 018708; The Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain; Grant number: ISCIII-RTICC RD06/0020/0035-FEDER; Ministerio de Educación y Ciencia, Madrid, Spain (Programa Hispano- Brasileño de Cooperación Universitaria); Grant number: PHB 2004-0800-PC; CAPES/Ministerio da Educaçao, Brasilia, Brazil; CNPq-Brazilian National Research Council, Brasilia, Brazil; FAPERJ-Rio de Janeiro Research Foundation, Rio de Janeiro, Brazil; Fundación Marcelino Botín, Madrid, Spain.Peer Reviewe

A Probabilistic Approach for the Evaluation of Minimal Residual Disease by Multiparameter Flow Cytometry in Leukemic B-Cell Chronic Lymphoproliferative Disorders

Multiparameter flow cytometry has become an essential too] for monitoring response to therapy in hematological malignancies, including B-cell chronic lymphoproliferative disorders (B-CLPD). However, depending on the expertise of the operator minimal residual disease (MRD) can be misidentified, given that data analysis is based on the definition of expert-based bidimensional plots, where an operator selects the subpopulations of interest. Here, we propose and evaluate a probabilistic approach based on pattern classification tools and the Bayes theorem, for automated analysis of flow cytometry data from a group of 50 B-CLPD versus normal peripheral blood B-cells under MRD conditions, with the aim of reducing operator-associated subjectivity. The proposed approach provided a tool for MRD detection in B-CLPD by flow cytometry with a sensitivity of <= 8 x 10(-5) (median of <= 2 x 10(-7)). Furthermore, in 86% of BCLPD cases tested, no events corresponding to normal B-cells were wrongly identified as belonging to the neoplastic B-cell population at a level of <= 10(-7). Thus, this approach based on the search for minimal numbers of neoplastic B-cells similar to those detected at diagnosis could potentially be applied with both a high sensitivity and specificity to investigate for the presence of MRD in virtually all B-CLPD. Further studies evaluating its efficiency in larger series of patients, where reactive conditions and non-neoplastic disorders are also included, are required to confirm these results. (C) 2008 International Society for Advancement of Cytometr

A probabilistic approach for the evaluation of minimal residual disease by multiparameter flow cytometry in leukemic B-cell chronic lymphoproliferative disorders

Multiparameter flow cytometry has become an essential tool for monitoring response to therapy in hematological malignancies, including B-cell chronic lymphoproliferative disorders (B-CLPD). However, depending on the expertise of the operator minimal residual disease (MRD) can be misidentified, given that data analysis is based on the definition of expert-based bidimensional plots, where an operator selects the subpopulations of interest. Here, we propose and evaluate a probabilistic approach based on pattern classification tools and the Bayes theorem, for automated analysis of flow cytometry data from a group of 50 B-CLPD versus normal peripheral blood B-cells under MRD conditions, with the aim of reducing operator-associated subjectivity. The proposed approach provided a tool for MRD detection in B-CLPD by flow cytometry with a sensitivity of ≤8 × 10-5 (median of ≤2 × 10-7). Furthermore, in 86% of B-CLPD cases tested, no events corresponding to normal B-cells were wrongly identified as belonging to the neoplastic B-cell population at a level of ≤10-7. Thus, this approach based on the search for minimal numbers of neoplastic B-cells similar to those detected at diagnosis could potentially be applied with both a high sensitivity and specificity to investigate for the presence of MRD in virtually all B-CLPD. Further studies evaluating its efficiency in larger series of patients, where reactive conditions and non-neoplastic disorders are also included, are required to confirm these results. © 2008 International Society for Advancement of Cytometry.European Commission (EuroFlow); Grant number: LSHB-CT-2006- 018708; The Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain; Grant number: ISCIII-RTICC RD06/0020/0035-FEDER; Ministerio de Educación y Ciencia, Madrid, Spain (Programa Hispano- Brasileño de Cooperación Universitaria); Grant number: PHB 2004-0800-PC; CAPES/Ministerio da Educaçao, Brasilia, Brazil; CNPq-Brazilian National Research Council, Brasilia, Brazil; FAPERJ-Rio de Janeiro Research Foundation, Rio de Janeiro, Brazil; Fundación Marcelino Botín, Madrid, Spain.Peer Reviewe