Germinal center B (GCB) and non‐GCB cell‐like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation

Costa, Luciano J.; Feldman, Andrew L.; Micallef, Ivana N.; Inwards, David J.; Johnston, Patrick B.; Porrata, Luis F.; Ansell, Stephen M.

doi:10.1111/j.1365-2141.2008.07207.x

Cited by 28 publications

(16 citation statements)

References 36 publications

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“…In order to strictly select an appropriate indication of HSCT, poorer prognostic groups need to be further discriminated by additional prognostic factors. As for DLBCL subtypes, the significance of the prognosis between GCB type and ABC type is controversial [26][27][28][29]. In the present study, there was a significant difference in PFS only between the GCB and non-GCB subgroups.…”

Section: Discussioncontrasting

confidence: 53%

Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens

et al. 2011

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Serum concentration of soluble interleukin-2 receptor (sIL-2R) predicts the clinical outcome of patients with aggressive non-Hodgkin's lymphoma treated with the cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen without rituximab. In the present study, we aim to re-assess the prognostic significance of serum sIL-2R for diffuse large B cell lymphoma (DLBCL) patients treated with CHOP plus rituximab and to assess sIL-2R with subtype of DLBCL, such as GCB type and non-GCB type. Two hundred and thirty-three patients with DLBCL were enrolled between December 2002 and March 2008. To evaluate serum levels of sIL-2R, venous blood samples were drawn from patients immediately before initiation of treatment. Serum sIL-2R was determined by sandwich enzyme-linked immunosorbent assay. The 5-year overall survival (OS) rates for patients with sIL-2R levels of ≥2,000 (110 cases) and <2,000 U/mL (123 cases) were 54.2% and 89.0% (P < 0.0001), respectively. Multivariate analysis using the proportional-hazards model revealed that serum sIL-2R (P = 0.0099) and extranodal involvement sites (P = 0.0392) were independent prognostic factors for OS and that clinical stage (P = 0.0168), performance status (P = 0.0181), sIL-2R (P = 0.0232), and LDH (P = 0.0316) were independent prognostic factors for progression-free survival in sIL-2R and every factor of the International Prognostic Index. Serum sIL-2R might be a useful prognostic factor for DLBCL patients in the rituximab era.

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Section: Discussioncontrasting

confidence: 53%

Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens

et al. 2011

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“…A recent IHC study in 59 DLBCL patients with chemosensitive disease undergoing HDC-ASCS demonstrated that germinal center B-cell-like and nongerminal center B-cell-like patients (defined by Hans criteria) did not differ in risk of progression or OS. 29 Nevertheless, among patients with MUM1-positive DLBCL, there was a trend for a higher risk of progression (P ¼ .08).…”

Section: Discussionmentioning

confidence: 97%

Higher response to lenalidomide in relapsed/refractory diffuse large B‐cell lymphoma in nongerminal center B‐cell–like than in germinal center B‐cell–like phenotype

Hernandez‐Ilizaliturri

Deeb

Zinzani

et al. 2011

Cancer

283

180

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BACKGROUND: There is a need to develop novel therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and to identify biomarkers predictive for therapeutic response. Lenalidomide was previously shown to induce an overall response rate (ORR) of 28% in patients with relapsed/refractory DLBCL. It is currently unknown if response rates differ between patients with different DLBCL subtypes. METHODS: The authors retrospectively evaluated clinical outcomes of patients with germinal center B-cell-like versus nongerminal center B-cell-like DLBCL treated with salvage lenalidomide at 4 academic institutions. RESULTS: Forty patients with relapsed/refractory DLBCL were included (24 men; 16 women; median age, 66 years; median of 4 prior treatments, including rituximab chemotherapy). Patients were classified as germinal center B-cell-like (n ¼ 23) or nongerminal center B-cell-like (n ¼ 17) DLBCL according to the Hans algorithm. The subgroups were similar in terms of stage, international prognostic index score, prior number of treatments, and rituximab resistance. A significant difference in clinical response to lenalidomide was observed in nongerminal center B-cell-like versus germinal center B-cell-like patients. ORR was 52.9% versus 8.7% (P ¼ .006); complete response rate was 23.5% versus 4.3%. Median progression-free survival was 6.2 versus 1.7 months (P ¼ .004), although no difference in OS was observed between nongerminal center B-cell-like and germinal center B-cell-like DLBCL patients. CONCLUSIONS: The data suggest that the 2 major subgroups of patients with DLBCL (germinal center B cell and nongerminal center B cell) have different antitumor responsiveness to lenalidomide in the relapsed/refractory setting. A large international trial (NCT01197560) has been opened to enrollment in an attempt to prospectively validate these retrospective observations. Cancer 2011;117:5058-

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“…GC or ABC type did not appear to be a factor determining outcome in patients with primary refractory or relapsed DLBCL (Costa et al , 2008).…”

Section: Impact On Clinical Outcomementioning

confidence: 99%

The role of BCL6 in lymphomas and routes to therapy

2010

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SummaryBCL6 is a transcription factor that has essential B-cell and T-cell roles in normal antibody responses. It is involved in chromosomal translocations in diffuse large B-cell lymphoma (DBCL; including primary mediastinal B-cell lymphoma) and nodular lymphocyte predominant Hodgkin lymphoma, and is expressed in follicular lymphoma and Burkitt's lymphoma. The neoplastic T-cells of angioimmunoblastic T-cell lymphoma also express BCL6. BCL6 prevents terminal B-cell differentiation largely through repression of PRDM1. In the ''cell of origin'' classification of DLBCL BCL6 is associated with the germinal centre subtype, which carries a good response to modern treatments. More recently, specific BCL6 antagonists, including small molecule inhibitors, have been developed. These antagonists have demonstrated that DLBCL cells, in which BCL6 is transcriptionally active, are dependent on this gene for survival. BCL6 antagonists are active against primary DLBCL and may find future application in the treatment of lymphomas.

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Germinal center B (GCB) and non‐GCB cell‐like diffuse large B cell lymphomas have similar outcomes following autologous haematopoietic stem cell transplantation

Cited by 28 publications

References 36 publications

Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens

Serum soluble interleukin-2 receptor (sIL-2R) level is associated with the outcome of patients with diffuse large B cell lymphoma treated with R-CHOP regimens

Higher response to lenalidomide in relapsed/refractory diffuse large B‐cell lymphoma in nongerminal center B‐cell–like than in germinal center B‐cell–like phenotype

The role of BCL6 in lymphomas and routes to therapy

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