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Background Extranodal nasal-type NK/T-cell lymphoma is a rare and severe disease. Considering the rarity of this lymphoma in Europe, we conducted a multicentric retrospective study on nasal-type NK/T cell lymphoma to determine the optimal induction strategy and identify prognostic factors. Methods Thirty-six adult patients with nasal-type NK/T-cell lymphoma were recruited and assessed. In total, 80 % of patients were classified as having upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20 % extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL). Results For advanced-stage disease, chemotherapy alone (CT) was the primary treatment (84 % vs. 10 % for combined CT + radiation therapy (RT), respectively), while for early-stage disease, 50 % of patients received the combination of CT + RT and 50 % CT alone. Five-year overall survival (OS) and progression-free survival (PFS) rates were 39 % and 33 %. Complete remission (CR) rates were significantly higher when using CT + RT (90 %) versus CT alone (33 %) (p < 0.0001). For early-stage disease, CR rates were 37 % for CT alone versus 100 % for CT + RT. Quality of response was significantly associated with survival, with 5-year OS being 80 % for CR patients versus 0 % for progressive disease patients (p  <  0.01). Conclusion Early RT concomitantly or sequentially with CT led to improved patient outcomes, with quality of initial response being the most important prognosticator for 5-year OS.

The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens. We aimed to assess, in patients aged 18–59 years, the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with standard treatment plus rituximab. We did an open-label randomised trial comparing dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) with subsequent consolidation versus standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Random assignment was done with a computer-assisted randomisation-allocation sequence with a block size of four. Patients were aged 18–59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1. Our primary endpoint was event-free survival. Our analyses of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00140595. One patient withdrew consent before treatment and 54 did not complete treatment. After a median follow-up of 44 months, our 3-year estimate of event-free survival was 81% (95% CI 75–86) in the R-ACVBP group and 67% (59–73) in the R-CHOP group (hazard ratio [HR] 0·56, 95% CI 0·38–0·83; p=0·0035). 3-year estimates of progression-free survival (87% [95% CI, 81–91] vs 73% [66–79]; HR 0·48 [0·30–0·76]; p=0·0015) and overall survival (92% [87–95] vs 84% [77–89]; HR 0·44 [0·28–0·81]; p=0·0071) were also increased in the R-ACVBP group. 82 (42%) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 (15%) of 183 in the R-CHOP group. Grade 3–4 haematological toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (38% [75 of 196] vs 9% [16 of 183]). Compared with standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18–59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index. Haematological toxic effects of the intensive regimen were raised but manageable. Groupe d'Etudes des Lymphomes de l'Adulte and Amgen.

Multiparametric flow cytometry has proven to be a powerful method for detection and immunophenotypic characterization of clonal subsets, particularly in lymphoproliferative disorders of the B-cell lineage. Although in theory promising, this approach has not been comparably fulfilled in mature T-cell malignancies. Specifically, the T-cell receptor-Vβ repertoire analysis in blood can provide strong evidence of clonality, particularly when a single expanded Vß family is detected. The purpose of this study was to determine the relevance of this approach when applied to biopsies, at the site of tumor involvement. To this end, 30 peripheral T-cell lymphoma and 94 control biopsies were prospectively studied. Vβ expansions were commonly detected within CD4+ or CD8+ T cells (97% of peripheral T-cell lymphoma and 54% of non-peripheral T-cell lymphoma cases); thus, not differentiating malignant from reactive processes. Interestingly, we demonstrated that using a standardized evaluation, the detection of a high Vβ expansion was closely associated with diagnosis of peripheral T-cell lymphoma, with remarkable specificity (98%) and sensitivity (90%). This approach also identified eight cases of peripheral T-cell lymphoma that were not detectable by other forms of immunophenotyping. Moreover, focusing Vβ expression analysis to T-cell subsets with aberrant immunophenotypes, we demonstrated that the T-cell clone might be heterogeneous with regard to surface CD7 or CD10 expression (4/11 cases), providing indication on ‘phenotypic plasticity’. Finally, among the wide variety of Vβ families, the occurrence of a Vβ17 expansion in five cases was striking. To our knowledge, this is the first report demonstrating the power of T-cell receptor-Vβ repertoire analysis by flow cytometry in biopsies as a basis for peripheral T-cell lymphoma diagnosis and precise T-cell clone identification and characterization.

Multiparametric flow cytometry has proven to be a powerful method for detection and immunophenotypic characterization of clonal subsets, particularly in lymphoproliferative disorders of the B-cell lineage. Although in theory promising, this approach has not been comparably fulfilled in mature T-cell malignancies. Specifically, the T-cell receptor-V[beta] repertoire analysis in blood can provide strong evidence of clonality, particularly when a single expanded Vß family is detected. The purpose of this study was to determine the relevance of this approach when applied to biopsies, at the site of tumor involvement. To this end, 30 peripheral T-cell lymphoma and 94 control biopsies were prospectively studied. V[beta] expansions were commonly detected within CD4+ or CD8+ T cells (97% of peripheral T-cell lymphoma and 54% of non-peripheral T-cell lymphoma cases); thus, not differentiating malignant from reactive processes. Interestingly, we demonstrated that using a standardized evaluation, the detection of a high V[beta] expansion was closely associated with diagnosis of peripheral T-cell lymphoma, with remarkable specificity (98%) and sensitivity (90%). This approach also identified eight cases of peripheral T-cell lymphoma that were not detectable by other forms of immunophenotyping. Moreover, focusing V[beta] expression analysis to T-cell subsets with aberrant immunophenotypes, we demonstrated that the T-cell clone might be heterogeneous with regard to surface CD7 or CD10 expression (4/11 cases), providing indication on 'phenotypic plasticity'. Finally, among the wide variety of V[beta] families, the occurrence of a V[beta]17 expansion in five cases was striking. To our knowledge, this is the first report demonstrating the power of T-cell receptor-V[beta] repertoire analysis by flow cytometry in biopsies as a basis for peripheral T-cell lymphoma diagnosis and precise T-cell clone identification and characterization.

BACKGROUND: Extranodal nasal-type NK/T-cell lymphoma is a rare and severe disease. Considering the rarity of this lymphoma in Europe, we conducted a multicentric retrospective study on nasaltype NK/T cell lymphoma to determine the optimal induction strategy and identify prognostic factors. METHODS: Thirty-six adult patients with nasal-type NK/T-cell lymphoma were recruited and assessed. In total, 80 % of patients were classified as having upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20 % extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL). RESULTS: For advanced-stage disease, chemotherapy alone (CT) was the primary treatment (84 % vs. 10 % for combined CT + radiation therapy (RT), respectively), while for early-stage disease, 50 % of patients received the combination of CT + RT and 50 % CT alone. Five-year overall survival (OS) and progression-free survival (PFS) rates were 39 % and 33 %. Complete remission (CR) rates were significantly higher when using CT + RT (90 %) versus CT alone (33 %) (p < 0.0001). For early-stage disease, CR rates were 37 % for CT alone versus 100 % for CT + RT. Quality of response was significantly associated with survival, with 5-year OS being 80 % for CR patients versus 0 % for progressive disease patients (p < 0.01). CONCLUSION: Early RT concomitantly or sequentially with CT led to improved patient outcomes, with quality of initial response being the most important prognosticator for 5-year OS.