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?
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.
Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, Republic of Korea.
Gyeong-Won
GW
Lee
Jung-Hun
JH
Kang
In-Suk
IS
Kim
Hoon-Gu
HG
Kim
Gyung Hyuck
GH
Ko
Jeong Hee
JH
Lee
Dong Chool
DC
Kim
Dae Hyun
DH
Song
Jung Wook
JW
Yang
Jong Sil
JS
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D019175:DNA Methylation; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D015999:Multivariate Analysis; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011241:Prednisone