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.

Autores de IIS La Fe

• Abelardo Garcia De Lorenzo Mateos

  Autor

• Lourdes Cordón Gallego

  Autor

• 

  Javier De La Rubia Comos

  Autor

• Joan Antoni Teixidor Sureda

  Autor

Participantes ajenos a IIS La Fe

• Paiva B
• Vídriales MB
• Montalbán MÁ
• Pérez JJ
• Gutiérrez NC
• Rosiñol L
• Martínez-López J
• Oriol A
• Terol MJ
• Echeveste MA
• De Paz R
• De Arriba F
• Palomera L
• Díaz-Mediavilla J
• Gorosquieta A
• Alegre A
• Martin A
• Lahuerta JJ
• Bladé J
• Orfao A
• San Miguel JF

Grupos

• Hematología y Hemoterapia

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.