Is inactivation of O6-methylguanine DNA methyltransferase still a favorable prognostic factor of patients with diffuse large B-cell lymphoma in the era of R-CHOP chemotherapy?

Leuk Lymphoma. 2009 Dec;50(12):1992-8. doi: 10.3109/10428190903312462.

Abstract

The prognostic significance of O6-methylguanine DNA methyltransferase (MGMT) inactivation was evaluated in patients with diffuse large B-cell lymphoma (DLBCL) who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in addition to rituximab. In this retrospective study, we used the methylation-specific polymerase chain reaction to investigate MGMT promoter methylation status and immunohistochemistry to evaluate MGMT expression in patients with DLBCL who received rituximab plus CHOP (R-CHOP) chemotherapy. No difference in patient characteristics, disease characteristics, response, or survival in patients with DLBCL who received front-line R-CHOP chemotherapy was observed according to MGMT methylation status and MGMT expression. On multivariate analysis, Grade 3-4 mucositis in the MGMT methylated group was significantly higher than that in the MGMT unmethylated group (hazard ratio (HR) 2.40, 95% CIs: 1.26-7.26, p = 0.014). This study demonstrated that inactivation of MGMT does not appear to play an important role in patients with DLBCL who received R-CHOP chemotherapy either with regard to the response rate or overall survival. Additionally, Grade 3-4 mucositis was found to be significantly related with inactivation of MGMT by a multivariate analysis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • DNA Methylation
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / enzymology
  • Male
  • Middle Aged
  • Mucositis / chemically induced
  • Multivariate Analysis
  • O(6)-Methylguanine-DNA Methyltransferase / antagonists & inhibitors*
  • O(6)-Methylguanine-DNA Methyltransferase / genetics
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism
  • Polymerase Chain Reaction / methods
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Rituximab
  • Survival Analysis
  • Vincristine / administration & dosage
  • Vincristine / adverse effects
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • O(6)-Methylguanine-DNA Methyltransferase
  • Prednisone