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. 2016 Mar 19:35:49.
doi: 10.1186/s13046-016-0324-0.

Flow cytometry remission by Ig light chains ratio is a powerful marker of outcome in multiple myeloma after tandem autologous transplant: a real-life study

Iole Cordone  1   2 , Francesco Marchesi  3 , Serena Masi  4 , Valentina Summa  4 , Francesco Pisani  3 , Roberta Merola  4 , Giovanni Cigliana  4 , Giulia Orlandi  4 , Svitlana Gumenyuk  3 , Francesca Palombi  3 , Atelda Romano  3 , Antonio Spadea  3 , Daniela Renzi  3 , Elena Papa  3 , Marco Canfora  5 , Laura Conti  4 , Maria Concetta Petti  3 , Andrea Mengarelli  3
Affiliations

Flow cytometry remission by Ig light chains ratio is a powerful marker of outcome in multiple myeloma after tandem autologous transplant: a real-life study

Iole Cordone et al. J Exp Clin Cancer Res. .

Abstract

Background: The achievement of complete response (CR) significantly correlates with a better clinical outcome in multiple myeloma (MM) patients treated with autologous stem cell transplant (ASCT). The depth of response is one of the most relevant factors to predict patient's outcome, however the definition of CR through standard criteria has shown several limitations.

Methods: In this study we evaluated the minimal residual disease (MRD) in 50 consecutive MM patients who underwent an up-front tandem ASCT in our center, using a single-tube six-colors flow cytometry assay (FC) based on intra-cytoplasmic immunoglobulin (cy-Ig) light chains ratio evaluated on patient-specific plasma cells (PC) immune profile, in a real-life setting.

Results: With a sensitivity up to 10(-5), clonal-PC were documented by FC in 36.4% (12/33) of patients in conventional CR after second transplant. The number of flow MRD-negative patients significantly increased after induction and first ASCT, but not between first and second transplant. The 5-years progression-free survival (5ys-PFS) of flow MRD-negative patients after second transplant was significantly better than patients who remained MRD-positive considering both all patients (5ys-PFS: 70% vs 5%) and patients in CR according to standard criteria (5ys-PFS: 67% vs 0%).

Conclusions: FC remission through cy-Ig light ratio on PC sub-populations is a sensitive, highly informative, low-cost and routinely applicable MRD assay, a powerful tool in treatment response evaluation and a crucial marker of outcome in MM.

Keywords: Autologous stem cell transplant; Flow cytometry remission; Light chains ratio; Minimal residual disease; Multiple myeloma.

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Figures

Fig. 1
Fig. 1
Flow cytometry gating strategy for MRD assessment: representative analysis of a bone marrow sample. a CD38bright PC population, b CD45+ Lymphocytes (Ly), c surface membrane expression of CD19 and CD56 assessed on CD38bright PC, d cy-Ig Kappa/Lambda ratio on CD19+ PC (normal; ratio 1.9); e cy-Ig Kappa/Lambda ratio on CD56+ PC (clonal; ratio 0.01); f cy-Ig Kappa/Lambda ratio on CD19+ Ly utilized as internal control (normal; ratio 1.8); g cy-Ig Kappa/Lambda ratio on the PC and Ly populations; h populations hierarchy
Fig. 2
Fig. 2
Patients in CR according to standard criteria and MRD negative from FC assessment in all check-points of the therapeutic program
Fig. 3
Fig. 3
5-years PFS curves according to MRD assessment by FC after second transplant: all patients (a); patients in CR according to standard criteria (b)
See this image and copyright information in PMC

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