1. Multiparameter flow cytometry evaluation of plasma cell DNA content and proliferation in 595 transplant-eligible patients with myeloma included in the Spanish GEM2000 and GEM2005<65y trials.
- Author
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Paiva B, Vídriales MB, Montalbán MÁ, Pérez JJ, Gutiérrez NC, Rosiñol L, Martínez-López J, Mateos MV, Cordón L, Oriol A, Terol MJ, Echeveste MA, De Paz R, De Arriba F, Palomera L, de la Rubia J, Díaz-Mediavilla J, Sureda A, Gorosquieta A, Alegre A, Martin A, Lahuerta JJ, Bladé J, Orfao A, and San Miguel JF
- Subjects
- Aged, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Cell Proliferation drug effects, Clone Cells, Disease-Free Survival, Dose-Response Relationship, Drug, Humans, Middle Aged, Multiple Myeloma drug therapy, Multivariate Analysis, Plasma Cells drug effects, Spain, DNA, Neoplasm metabolism, Flow Cytometry methods, Multiple Myeloma pathology, Multiple Myeloma therapy, Plasma Cells metabolism, Stem Cell Transplantation
- Abstract
The incorporation of high-dose therapy/autologous stem cell transplantation (HDT/ASCT) and novel agents has significantly improved survival in patients with multiple myeloma (MM), but whether this improvement also benefits patients harboring poor prognostic features, such as nonhyperdiploid MM (NH-MM) and a high proliferation index, remains largely unknown. We analyzed the DNA content and proliferation index of bone marrow plasma cells (PCs) by multiparameter flow cytometry in 595 newly diagnosed transplant-eligible patients with MM included in two consecutive PETHEMA/GEM trials: GEM2000 [VBMCP/VBAD (vincristine, carmustine, melphalan, cyclophosphamide, prednisone/vincristine, bischloroethylnitrosourea, adriamycin, and dexamethasone) followed by HDT/ASCT; n = 319] and GEM2005<65y (randomized induction with VBMCP/VBAD/bortezomib or thalidomide/dexamethasone or bortezomib/thalidomide/dexamethasone followed by HDT/ASCT; n = 276). Of the 595 patients, 295 were classified as NH-MM (49.6%) and 336 (56.5%) as high-proliferative MM (≥1% PCs in S-phase). Detection of NH-MM DNA content and ≥1% PCs in S-phase were of independent prognostic value for overall survival. Treatment with bortezomib-based regimens abrogated the inferior overall survival of patients with ≥1% PCs in S-phase but not of patients with NH-MM. Finally, a comparative analysis of PC proliferation index at diagnosis versus disease progression showed a twofold increase at relapse in 44 of 52 patients (85%) analyzed at both time points. NH-MM and a high proliferation index assessed by multiparameter flow cytometry remain as independent prognostic factors in MM, but the latter may be overcome by incorporating novel agents in the HDT/ASCT setting., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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