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1.
Ann Oncol ; 22(7): 1601-1607, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21199885

ABSTRACT

BACKGROUND: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) shows poor prognosis and frequent central nervous system (CNS) relapses under anthracycline-containing chemotherapy. The aim of this study was to determine the prognosis and CNS relapse incidence of CD5+ DLBCL in the rituximab era. PATIENTS AND METHODS: We analyzed 337 patients with CD5+ DLBCL who received chemotherapy with (R-chemotherapy group; n = 184) or without (chemotherapy group; n = 153) rituximab. RESULTS: No significant difference was found in clinical background comparisons between the two groups. In the R-chemotherapy group, 60% of the patients were older than 65 years at diagnosis. Both the complete response rate and overall survival (OS) were significantly better in the R-chemotherapy group (P = 0.0003 and P = 0.002, respectively). Multivariate analysis confirmed that chemotherapy without rituximab was associated with unfavorable OS. However, the probability of CNS relapse did not differ between the two groups (P = 0.89). The CNS relapse was strongly associated with short OS (P < 0.0001). In the R-chemotherapy group, 83% of patients who experienced CNS relapse had parenchymal disease. CONCLUSIONS: Our results indicate that rituximab improves the OS of patients with CD5+ DLBCL but does not decrease the CNS relapse rate. More effective treatments with CNS prophylaxis are needed for CD5+ DLBCL patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , CD5 Antigens/metabolism , Lymphoma, Large B-Cell, Diffuse/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Brain Neoplasms/metabolism , Brain Neoplasms/secondary , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Prednisone/administration & dosage , Remission Induction , Retrospective Studies , Rituximab , Survival Rate , Treatment Outcome , Vincristine/administration & dosage , Young Adult
2.
Ann Oncol ; 21(6): 1217-1221, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19884246

ABSTRACT

BACKGROUND: A recent laboratory study indicated that statins impaired the antitumor effects of rituximab by inducing conformational changes in CD20. Although these findings raised significant concerns about statin use during rituximab treatment, their clinical significance is unclear. PATIENTS AND METHODS: We conducted a retrospective study investigating the effects of statins on the prognosis of diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Newly diagnosed DLBCL patients were analyzed (n = 256), including 35 patients taking statins. RESULTS: The 3-year progression-free survival rates were 84% and 73% (P = 0.38), while the overall survival rates were 89% and 78% (P = 0.28) for those patients treated with and without statins, respectively. After adjusting for the International Prognostic Index and serum cholesterol level, statin use was not associated with prognosis. CONCLUSIONS: These results indicate that statins do not influence the clinical prognosis of DLBCL treated with RCHOP. Further studies with larger numbers of patients are warranted to confirm the prognostic significance of statins for patients with DLBCL receiving rituximab-containing chemotherapy.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Drug Antagonism , Female , Humans , Immunotherapy , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Prednisone/therapeutic use , Prognosis , Retrospective Studies , Rituximab , Survival Analysis , Vincristine/therapeutic use , Young Adult
3.
Ann Oncol ; 20(3): 526-33, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19074749

ABSTRACT

BACKGROUND: Soluble interleukin-2 receptor (SIL-2R) is known to be a prognostic parameter in patients with diffuse large B-cell lymphoma (DLBCL) receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy. However, its prognostic value has not been well known since the introduction of rituximab. PATIENTS AND METHODS: We retrospectively evaluated the prognostic impact of SIL-2R in 228 DLBCL patients, comparing 141 rituximab-combined CHOP (RCHOP)-treated patients with 87 CHOP-treated patients as a historical control. RESULTS: Patients with high serum SIL-2R showed significantly poorer event-free survival (EFS) and overall survival (OS) than patients with low SIL-2R in both the RCHOP group (2-year EFS, 66% versus 92%, P<0.001; OS, 82% versus 95%, P=0.005) and the CHOP group (2-year EFS, 40% versus 82%; OS, 61% versus 90%, both P<0.001). Multivariate analysis including the five parameters of International Prognostic Index (IPI) and two-categorized IPI revealed that SIL-2R was an independent prognostic factor for EFS and OS in the RCHOP group as well as in the CHOP group. CONCLUSIONS: Our results demonstrate that SIL-2R retains its prognostic value in the rituximab era. The prognostic value of SIL-2R in DLBCL patients receiving rituximab-combined chemotherapy should be reassessed on a larger scale and by long-term follow-up.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Lymphoma, Large B-Cell, Diffuse/drug therapy , Receptors, Interleukin-2/metabolism , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Female , Humans , Lymphoma, Large B-Cell, Diffuse/metabolism , Male , Middle Aged , Prednisone/administration & dosage , Prednisone/therapeutic use , Retrospective Studies , Rituximab , Vincristine/administration & dosage , Vincristine/therapeutic use
4.
Ann Oncol ; 19(11): 1921-6, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18573805

ABSTRACT

BACKGROUND: Several biomarkers indicating poor prognosis have been reassessed in patients receiving rituximab combination chemotherapy for diffuse large B-cell lymphoma (DLBCL). However, few studies have investigated outcome in relation to a combination of these biomarkers. In addition, no large-scale studies have reassessed the outcome of patients with CD5-positive DLBCL treated with rituximab. PATIENTS AND METHODS: We conducted a retrospective study and investigated the predictive value of three biomarkers -- BCL2, germinal center (GC) phenotype and CD5 -- in 121 DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone. RESULTS: CD5-positive patients showed significantly poorer event-free survival (EFS) and overall survival (OS) than CD5-negative patients (2-year EFS, 18% versus 73%, P < 0.001; 2-year OS, 45% versus 91%, P = 0.001). However, no significant difference in outcome according to BCL2 or GC phenotype was observed. Multivariate analysis revealed that CD5 expression was a significant prognostic factor for EFS [hazard ratio 14.2, 95% confidence interval (CI) 4.7-43.2] and OS (hazard ratio 20.3, 95% CI 3.6-114.4). CONCLUSIONS: CD5 expression was the only significant prognostic factor among the biomarkers examined in this study. Further studies with larger numbers are warranted to confirm the prognostic significance of CD5 expression for patients with DLBCL receiving rituximab-containing chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/biosynthesis , CD5 Antigens/biosynthesis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm Staging , Phenotype , Prednisone/administration & dosage , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Rituximab , Vincristine/administration & dosage
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