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Leukemia-cell proliferation and disease progression in patients with early stage chronic lymphocytic leukemia.
Murphy, E J; Neuberg, D S; Rassenti, L Z; Hayes, G; Redd, R; Emson, C; Li, K; Brown, J R; Wierda, W G; Turner, S; Greaves, A W; Zent, C S; Byrd, J C; McConnel, C; Barrientos, J; Kay, N; Hellerstein, M K; Chiorazzi, N; Kipps, T J; Rai, K R.
Afiliación
  • Murphy EJ; Department of Medicine, University of California, San Francisco, CA, USA.
  • Neuberg DS; KineMed Inc., Emeryville, CA, USA.
  • Rassenti LZ; Dana Farber Cancer Institute, Boston, MA, USA.
  • Hayes G; CLL Research Consortium, San Diego, CA, USA.
  • Redd R; CLL Research Consortium, San Diego, CA, USA.
  • Emson C; Department of Medicine, Moores Cancer Center, University of California, San Diego, CA, USA.
  • Li K; KineMed Inc., Emeryville, CA, USA.
  • Brown JR; Dana Farber Cancer Institute, Boston, MA, USA.
  • Wierda WG; KineMed Inc., Emeryville, CA, USA.
  • Turner S; KineMed Inc., Emeryville, CA, USA.
  • Greaves AW; Dana Farber Cancer Institute, Boston, MA, USA.
  • Zent CS; CLL Research Consortium, San Diego, CA, USA.
  • Byrd JC; CLL Research Consortium, San Diego, CA, USA.
  • McConnel C; Department of Medicine, M. D. Anderson Cancer Center, Houston, TX, USA.
  • Barrientos J; KineMed Inc., Emeryville, CA, USA.
  • Kay N; CLL Research Consortium, San Diego, CA, USA.
  • Hellerstein MK; Department of Medicine, Moores Cancer Center, University of California, San Diego, CA, USA.
  • Chiorazzi N; CLL Research Consortium, San Diego, CA, USA.
  • Kipps TJ; Department of Medicine, Mayo Clinic, Rochester, MN, USA.
  • Rai KR; CLL Research Consortium, San Diego, CA, USA.
Leukemia ; 31(6): 1348-1354, 2017 06.
Article en En | MEDLINE | ID: mdl-28115735
ABSTRACT
The clinical course of patients with recently diagnosed early stage chronic lymphocytic leukemia (CLL) is highly variable. We examined the relationship between CLL-cell birth rate and treatment-free survival (TFS) in 97 patients with recently diagnosed, Rai stage 0-II CLL in a blinded, prospective study, using in vivo 2H2O labeling. Birth rates ranged from 0.07 to 1.31% new cells per day. With median follow-up of 4.0 years, 33 subjects (34%) required treatment by NCI criteria. High-birth rate was observed in 44% of subjects and was significantly associated with shorter TFS, unmutated IGHV status and expression of ZAP70 and of CD38. In multivariable modeling considering age, gender, Rai stage, expression of ZAP70 or CD38, IGHV mutation status and FISH cytogenetics, only CLL-cell birth rate and IGHV mutation status met criteria for inclusion. Hazard ratios were 3.51 (P=0.002) for high-birth rate and 4.93 (P<0.001) for unmutated IGHV. The association between elevated birth rate and shorter TFS was observed in subjects with either mutated or unmutated IGHVs, and the use of both markers was a better predictor of TFS than either parameter alone. Thus, an increased CLL birth rate in early stage disease is a strong predictor of disease progression and earlier treatment.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Biomarcadores de Tumor / Proliferación Celular / Mutación Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B / Biomarcadores de Tumor / Proliferación Celular / Mutación Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos