title: CD4(+) tumor infiltrating lymphocytes are prognostic and independent of R-IPI in patients with DLBCL receiving R-CHOP chemo-immunotherapy.
abstract: Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P < 0.001). Consistent with previous reports, systemic immunity also predicted outcome (86% OS for high lymphocyte to monocyte ratio [LMR], versus 63% with low LMR, P = 0.01). Multivariate analysis confirmed LMR as independently prognostic. Flow cytometry on fresh diagnostic lymphoma tissue, identified CD4(+) T-cell infiltration as the most significant predictor of outcome with ≥23% infiltration dividing the cohort into high and low risk groups with regard to event-free survival (EFS, P = 0.007) and OS (P = 0.003). EFS and OS were independent of the R-IPI and LMR. Importantly, within very good/good R-IPI patients, CD4(+) T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P = 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP.
authors: Queensland Institute of Medical Research, Brisbane, Queensland, Australia. colm_keane@health.qld.gov.au
authors: Colm
authors: C
authors: Keane
authors: Devinder
authors: D
authors: Gill
authors: Frank
authors: F
authors: Vari
authors: Donna
authors: D
authors: Cross
authors: Lynn
authors: L
authors: Griffiths
authors: Maher
authors: M
authors: Gandhi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology*; D015999:Multivariate Analysis; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012306:Risk; D000069283:Rituximab; D016019:Survival Analysis; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone