title: 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.
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.
authors.affiliation: Hospital Universitario de Salamanca, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Vídriales
authors.forename: María-Ángeles
authors.initials: MÁ
authors.lastname: Montalbán
authors.forename: José J
authors.initials: JJ
authors.lastname: Pérez
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Joaquín
authors.initials: J
authors.lastname: Martínez-López
authors.forename: María-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Lourdes
authors.initials: L
authors.lastname: Cordón
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: María-José
authors.initials: MJ
authors.lastname: Terol
authors.forename: María-Asunción
authors.initials: MA
authors.lastname: Echeveste
authors.forename: Raquel
authors.initials: R
authors.lastname: De Paz
authors.forename: Felipe
authors.initials: F
authors.lastname: De Arriba
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: Joaquín
authors.initials: J
authors.lastname: Díaz-Mediavilla
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Ana
authors.initials: A
authors.lastname: Gorosquieta
authors.forename: Adrian
authors.initials: A
authors.lastname: Alegre
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martin
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000378:metabolism*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy*; D015999:Multivariate Analysis; D010950:Plasma Cells / Q000187:drug effects / Q000378:metabolism*; D013030:Spain; D033581:Stem Cell Transplantation
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm