Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study

Pfreundschuh, Michael; Ho, Anthony D.; Cavallin‐Ståhl, Eva; Wolf, Max; Pettengell, Ruth; Vášová, Ingrid; Belch, Andrew R.; Walewski, Jan; Zinzani, Pier Luigi; Mingrone, Walter; Kvaløy, Stein; Shpilberg, Ofer; Jaeger, Ulrich; Hansen, Mads; Corrado, Claudia; Scheliga, Adriana; Loeffler, Markus; Kuhnt, Evelyn

doi:10.1016/s1470-2045(08)70078-0

Cited by 198 publications

(150 citation statements)

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“…For the rest of the group, the clinical findings were: stage I (29%), II (21%), III (22%), and IV (28%); B-symptoms (34%), elevated lactate dehydrogenase (67%); International Prognostic Index of 0-1 (low; 42%), 2 (low-intermediate; 24%), 3 (high-intermediate; 20%), 4-5 (high; 15%), and mean largest tumor mass of 5.7 ± 3.5 cm (range 1-18; 16% 410 cm, ie, bulky disease). 29 After therapy, complete remission was achieved in 424 (75%) patients, partial remission in 75 (13%), stable disease in 25 (4%), and 39 (7%) had progressive disease. Within the mean observation period of 43.4 months (range 1-140, median 40), there were 184 recurrences and 212 (38%) patients died, 147 (26%) of whom died of/with disease.…”

Section: Patient Characteristicsmentioning

confidence: 98%

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

et al. 2014

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In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using break-apart probes and IGH/MYC dual-fusion probes. Concurrent BCL2 and BCL6 aberrations were also assessed. Data were correlated with clinicopathological variables and prognostic parameters. MYC rearrangements were observed in 39/432 evaluable cases (9%), including 4 rearrangements detectable only with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P ¼ 0.02), MYC protein expression (P ¼ 0.032), and larger tumor mass size (P ¼ 0.0003). Patients with MYC rearrangements were more likely to be treatment resistant (Po0.0001). All types of MYC rearrangements were associated with poorer disease-specific survival, that is, 20/39 dead, median disease-specific survival 42 months, compared with 98/393 dead among the nonrearranged cases, median disease-specific survival not reached (P ¼ 0.0002). Cases with MYC rearrangements that overexpressed MYC protein were at risk with respect to disease-specific survival independent of the International Prognostic Index (P ¼ 0.046 and Po0.001, respectively). Presence of concurrent BCL2 aberrations but not of BCL6 aberrations was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC

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Section: Patient Characteristicsmentioning

confidence: 98%

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

et al. 2014

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“…Moreover, the predictive significance of some prognostic factors changed following the introduction of a CD20 monoclonal antibody, rituximab, underscores the necessity for revaluating the prognostic value of predictive factors after the introduction of rituximab (7,16).…”

Section: Introductionmentioning

confidence: 99%

“…The impact of BCL2 overexpression on survival in DLBCL is still debatable in previous studies. Additionally, the prognostic value of BCL2 protein overexpression is also different between GCB and ABC subtypes (14,15).Moreover, the predictive significance of some prognostic factors changed following the introduction of a CD20 monoclonal antibody, rituximab, underscores the necessity for revaluating the prognostic value of predictive factors after the introduction of rituximab (7,16).In the present study, we intended to investigate the optimal prognosis cut off value of Ki-67 index in DLBCL patients, and to confirm the specific prognostic value of BCL2 and its association with cell of origin classification (COOC). Furthermore, we investigated whether the BCL2/Ki-67 index has a more significant importance on the outcome of DLBCL patients.…”

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confidence: 99%

BCL2/Ki-67 index predict survival in germinal center B-cell-like diffuse large B-cell lymphoma

Tang

Zhou

Cheng³

et al. 2017

Oncology Letters

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Abstract. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. BCL2 apoptosis regulator (BCL2) and marker of proliferation are established prognostic markers, which have traditionally been assessed separately in DLBCL. However, no studies have evaluated the prognostic value of the combination of BCL2 and Ki-67 index. Thus, the present study aimed to analyze the prognostic value of combination of these two markers. Immunohistochemical analysis was used to assess the expression of BCL2 and Ki-67 in 274 cases of DLBCL. The BCL2/Ki-67 index demonstrated a significant association with decreased overall and progression free survival of patients with DLBCL, particularly for the germinal center B-cell-like subtype of DLBCL. Following multivariate analysis, the BCL2/Ki-67 index retained prognostic significance. Patients with coexpression of BCL2 and Ki-67 constituted a unique group with poor survival, thus novel therapies targeting BCL2 protein and high proliferative activity may improve the outcome of these patients. IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for 30-40% of all NHL patients (1-3), which is considered to be a heterogeneous entity based on its biological characteristics and clinical outcomes (3-5). The survivals of DLBCL patients have notably improved since addition of rituximab to CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy (6,7). However, some DLBCL patients continue to present an inferior prognosis under standard R-CHOP therapy (1).Ki-67, a nuclear nonhistone protein, is synthesized at the beginning of cell proliferation (8). Ki-67 expression has been widely used in clinical practice as an index to evaluate the proliferative activity of lymphoma. High Ki-67 expression was highly associated with worse OS for NHL (9). However, the relationship between Ki-67 expression and outcome with DLBCL are still contradictory and inconclusive in various studies (10-12).BCL2 protein functions as an antiapoptotic protein inhibiting cells from programmed cell death (13). Both gene amplification and translocation are common mechanisms causing BCL2 protein overexpression in DLBCL. The clinical significance of BCL2 protein expression in DLBCL is still controversial. The impact of BCL2 overexpression on survival in DLBCL is still debatable in previous studies. Additionally, the prognostic value of BCL2 protein overexpression is also different between GCB and ABC subtypes (14,15).Moreover, the predictive significance of some prognostic factors changed following the introduction of a CD20 monoclonal antibody, rituximab, underscores the necessity for revaluating the prognostic value of predictive factors after the introduction of rituximab (7,16).In the present study, we intended to investigate the optimal prognosis cut off value of Ki-67 index in DLBCL patients, and to confirm the specific prognostic value of BCL2 and its association with cell of origin classification (CO...

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“…[1][2][3][4] Although R-CHOP improves both the overall response rate (ORR) and overall survival (OS), there remains room for improvement because ϳ 20%-40% of patients still relapse after R-CHOP. [1][2][3][4] Epratuzumab is a humanized monoclonal IgG1 antibody directed against the B-cell specific antigen, CD22. 5,6 CD22 is a 135-kDa transmembrane phosphoglycoprotein expressed by pre-B and mature, normal B cells.…”

Section: Introductionmentioning

confidence: 99%

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

Micallef

Maurer

Wiseman

et al. 2011

Blood

135

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Prognostic significance of maximum tumour (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study

Cited by 198 publications

References 41 publications

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

BCL2/Ki-67 index predict survival in germinal center B-cell-like diffuse large B-cell lymphoma

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

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