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Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL.
GLA - German Lymphoma Alliance

Abstract (Expand)

The survival of diffuse large B-cell lymphoma patients varies considerably, reflecting the molecular diversity of tumors. In view of the controversy whether cytologic features, immunohistochemical … markers or gene expression signatures may capture this molecular diversity, we investigated which features provide prognostic information in a prospective trial in the R-CHOP treatment era. Within the cohort of DLBCLs patients treated in the RICOVER-60 trial of the German High-Grade Lymphoma Study Group (DSHNHL), we tested the prognostic impact of IB morphology in 949 patients. The expression of immunohistochemical markers CD5, CD10, BCL2, BCL6, human leukocyte antigen (HLA)-DR, interferon regulatory factor-4/multiple myeloma-1 (IRF4/MUM1), and Ki-67 was assessed in 506 patients. Expression of the immunohistochemical markers tested was of modest, if any, prognostic relevance. Moreover, the Hans algorithm using the expression patterns of CD10, BCL6, and interferon regulatory factor-4/multiple myeloma-1 failed to show prognostic significance in the entire cohort as well as in patient subgroups. IB morphology, however, emerged as a robust, significantly adverse prognostic factor in multivariate analysis, and its diagnosis showed a good reproducibility among expert hematopathologists. We conclude, therefore, that IB morphology in DLBCL is likely to capture some of the adverse molecular alterations that are currently not detectable in a routine diagnostic setting, and that its recognition has significant prognostic power.

Authors: G. Ott, M. Ziepert, W. Klapper, H. Horn, M. Szczepanowski, H. W. Bernd, C. Thorns, A. C. Feller, D. Lenze, M. Hummel, H. Stein, H. K. Muller-Hermelink, M. Frank, M. L. Hansmann, T. F. Barth, P. Moller, S. Cogliatti, M. Pfreundschuh, N. Schmitz, L. Trumper, M. Loeffler, A. Rosenwald

Date Published: 2nd Dec 2010

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Impact of rituximab and radiotherapy on outcome of patients with aggressive B-cell lymphoma and skeletal involvement.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: To study clinical presentation, outcome, and the role of radiotherapy in patients with aggressive B-cell lymphoma and skeletal involvement treated with and without rituximab. PATIENTS AND … METHODS: Outcome of patients with skeletal involvement was analyzed in a retrospective study of nine consecutive prospective trials of the German High-Grade Non-Hodgkin lymphoma Study Group. RESULTS: Of 3,840 patients, 292 (7.6%) had skeletal involvement. In the MabThera International Trial (MInT) for young good-prognosis patients and the Rituximab With CHOP Over 60 Years (RICOVER-60) study for elderly patients, the randomized addition of rituximab improved event-free survival (EFS; hazard ratio for MInT [HRMInT] = 0.4, P > 001; hazard ratio for RICOVER-60 [HRRICOVER-60] = 0.6, P > .001) and overall survival (OS; HRMInT = 0.4, P < .001; HRRICOVER-60 = 0.7, P = .002) in patients without skeletal involvement, but failed to improve the outcome of patients with skeletal involvement (EFS: HRMInT = 1.4, P = .444; HRRICOVER-60 = 0.8, P = .449; OS: HRMInT = 0.6, P = .449; HRRICOVER-60 = 1.0, P = .935). Skeletal involvement was associated with a worse outcome after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (HREFS = 1.5, P = .048; HROS = 1.1; P = .828), but not after CHOP without rituximab (HREFS = 0.8, P = .181; HROS = 0.7, P = .083). In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a decreased risk (HREFS = 0.3, P = .001; HROS = 0.5; P = .111). CONCLUSION: Rituximab failed to improve the outcome of patients with diffuse large B-cell lymphoma with skeletal involvement, although our data suggest a beneficial effect of radiotherapy to sites of skeletal involvement. Whether radiotherapy to sites of skeletal involvement can be spared in cases with a negative positron emission tomography after immunochemotherapy should be addressed in appropriately designed prospective trials.

Authors: G. Held, S. Zeynalova, N. Murawski, M. Ziepert, B. Kempf, A. Viardot, M. Dreyling, M. Hallek, M. Witzens-Harig, J. Fleckenstein, C. Rube, C. Zwick, B. Glass, N. Schmitz, M. Pfreundschuh

Date Published: 10th Nov 2013

Publication Type: Not specified

Human Diseases: B-cell lymphoma

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