Ki-67 expression as a prognostic factor in diffuse large B-cell lymphoma patients treated with rituximab plus CHOP

Eur J Haematol. 2010 Aug;85(2):149-57. doi: 10.1111/j.1600-0609.2010.01467.x. Epub 2010 May 6.

Abstract

Background: Assessment of tumor cell proliferation based on Ki-67 expression yielded conflicting prognostic predictions of patients with diffuse large B-cell lymphoma (DLBCL). The introduction of rituximab to the DLBCL treatment regime has led to alterations in the significance of previous prognostic factors.

Methods: We analyzed Ki-67 expression and its correlation with prognosis in 144 patients with DLBCL treated with rituximab plus CHOP (R-CHOP) between July 2003 and January 2008.

Results: The complete response (CR) rates following R-CHOP administration were not significantly different, based on Ki-67 expression status (P = 0.104). However, higher rates of relapse were observed in the high Ki-67 expression group (Ki-67 >or= 85%, n = 46) with 25.0%, compared to 10.0% in the low Ki-67 expression group (Ki-67 < 85%, n = 88) (P = 0.040). The 2-yr event-free survival (EFS) rates were 44.3% and 74.1% in the high and low Ki-67 expression groups, respectively (P = 0.011). The 2-yr overall survival (OS) rate was 66.4% in the high Ki-67 expression group and 82.2% in the low Ki-67 expression group (P = 0.016). In multivariate analysis, Ki-67 expression was a significant prognostic factor for EFS [hazard ratio (HR) = 2.909; 95% confidence interval (CI) 1.261-6.708; P = 0.012]. Ki-67 was associated with OS but with borderline significance (HR = 2.876; 95% CI, 0.972-8.508; P = 0.056).

Conclusion: Elevated Ki-67 expression seems to be associated with higher relapse after CR and inferior EFS in patients with DLBCL treated with R-CHOP.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell Proliferation / drug effects
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Humans
  • Ki-67 Antigen / analysis*
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / mortality*
  • Middle Aged
  • Prednisone / administration & dosage
  • Prognosis
  • Recurrence
  • Rituximab
  • Survival Analysis
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Ki-67 Antigen
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol