PATIENTS WITH PRIMARY CNS LYMPHOMA OR PRIMARY TESTICULAR DIFFUSE LARGE B-CELL LYMPHOMA HAVE AN INFERIOR PROGNOSIS WHEN CO-EXPRESSING C-MYC AND BCL2.
(Abstract release date: 05/19/16)
EHA Library. Troppan K. 06/09/16; 132524; E975
Dr. Katharina Troppan
Contributions
Contributions
Abstract
Abstract: E975
Type: Eposter Presentation
Background
Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal diffuse large B-cell lymphomas (DLBCLs) exhibiting a similar genetic signature and are characterised by an inferior response to current treatment regimens. DLBCL can be stratified by cell of origin (COO) derivation into the prognostically favorable germinal center B-cell (GCB)–like and the unfavorable activated B-cell (ABC) or non-GCB-like subtype based on gene expression signatures or immunohistochemical determination. The majority of PCNSL or PTL lymphoma derives from the non-GCB subtype. Recently, DLBCL patients with an immunohistochemical co-expression of c-MYC and BCL2 demonstrated inferior prognosis suggesting that concurrent expression of MYC/BCL2, termed double-protein-expression lymphoma (DPL), is a predictor of prognosis. Up to now there are no data, investigating the impact of DHL in patients with PCNSL or PTL.
Aims
We determined the frequency of DPL in a single center cohort of PCNSL or PTL and evaluated patients’ outcome in contrast to “standard” DLBCL not exhibiting concurrent expression of MYC/BCL2.
Methods
We evaluated retrospectively the appearance of DPL in 42 patients with CNS or testicular DLBCL, consecutively diagnosed and treated between 2004 and 2014 at our institution. To determine the double-hit score, immunohistochemistry for c-MYC and BCL2 was performed on diagnostic samples. Furthermore, the Choi algorithm was used to subclassify samples by cell-of-origin. On the basis of immunohistochemical c-MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group was defined by high expression of both MYC and BCL2 protein.
Results
Except for 3 samples, all patients were classified as non-GCB subtype. For 7 patients, no classification according to cell-of-origin could be performed. Of 42 primary extranodal DLBCL (PCNSL, n=28, PTL, n= 14), 29 patients were evaluable, 5 of them showed a double-hit score of 0, 11 patients had a DHS of 1, and 13 a DHS of 2, respectively. Using Kaplan-Meier curves and log-rank tests, probably due to small sample size, we could not demonstrate a significant different outcome for PCNSL or PTL patients with the non-GCB subtype as compared to the GCB subtype (p=0.74). However, we could clearly demonstrate a significant impaired outcome for patients with DHS of 2 (OS 61 versus 7 months, p=0.01) (Figure 1). Particularly, for patients with non-GCB subtype, we were able to further discriminate a subgroup of patients with an even worse clinical outcome to standard treatment (p=0.007).
Conclusion
: In this single center cohort, we could demonstrate a significant negative effect on OS for PCNSL or testicular large cell lymphoma patients co-expressing MYC and BCL2. We could further define a subgroup of patients within the non-GCB cohort demonstrating double hit positivity (DHS of 2) that is associated with a particular short survival. These non-GCB-, DHS positive DLBCL patients are candidates for novel therapeutic strategies.
Session topic: E-poster
Keyword(s): BCL2, Diffuse large B cell lymphoma, MYC
Type: Eposter Presentation
Background
Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal diffuse large B-cell lymphomas (DLBCLs) exhibiting a similar genetic signature and are characterised by an inferior response to current treatment regimens. DLBCL can be stratified by cell of origin (COO) derivation into the prognostically favorable germinal center B-cell (GCB)–like and the unfavorable activated B-cell (ABC) or non-GCB-like subtype based on gene expression signatures or immunohistochemical determination. The majority of PCNSL or PTL lymphoma derives from the non-GCB subtype. Recently, DLBCL patients with an immunohistochemical co-expression of c-MYC and BCL2 demonstrated inferior prognosis suggesting that concurrent expression of MYC/BCL2, termed double-protein-expression lymphoma (DPL), is a predictor of prognosis. Up to now there are no data, investigating the impact of DHL in patients with PCNSL or PTL.
Aims
We determined the frequency of DPL in a single center cohort of PCNSL or PTL and evaluated patients’ outcome in contrast to “standard” DLBCL not exhibiting concurrent expression of MYC/BCL2.
Methods
We evaluated retrospectively the appearance of DPL in 42 patients with CNS or testicular DLBCL, consecutively diagnosed and treated between 2004 and 2014 at our institution. To determine the double-hit score, immunohistochemistry for c-MYC and BCL2 was performed on diagnostic samples. Furthermore, the Choi algorithm was used to subclassify samples by cell-of-origin. On the basis of immunohistochemical c-MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group was defined by high expression of both MYC and BCL2 protein.
Results
Except for 3 samples, all patients were classified as non-GCB subtype. For 7 patients, no classification according to cell-of-origin could be performed. Of 42 primary extranodal DLBCL (PCNSL, n=28, PTL, n= 14), 29 patients were evaluable, 5 of them showed a double-hit score of 0, 11 patients had a DHS of 1, and 13 a DHS of 2, respectively. Using Kaplan-Meier curves and log-rank tests, probably due to small sample size, we could not demonstrate a significant different outcome for PCNSL or PTL patients with the non-GCB subtype as compared to the GCB subtype (p=0.74). However, we could clearly demonstrate a significant impaired outcome for patients with DHS of 2 (OS 61 versus 7 months, p=0.01) (Figure 1). Particularly, for patients with non-GCB subtype, we were able to further discriminate a subgroup of patients with an even worse clinical outcome to standard treatment (p=0.007).
Conclusion
: In this single center cohort, we could demonstrate a significant negative effect on OS for PCNSL or testicular large cell lymphoma patients co-expressing MYC and BCL2. We could further define a subgroup of patients within the non-GCB cohort demonstrating double hit positivity (DHS of 2) that is associated with a particular short survival. These non-GCB-, DHS positive DLBCL patients are candidates for novel therapeutic strategies.
Session topic: E-poster
Keyword(s): BCL2, Diffuse large B cell lymphoma, MYC
Abstract: E975
Type: Eposter Presentation
Background
Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal diffuse large B-cell lymphomas (DLBCLs) exhibiting a similar genetic signature and are characterised by an inferior response to current treatment regimens. DLBCL can be stratified by cell of origin (COO) derivation into the prognostically favorable germinal center B-cell (GCB)–like and the unfavorable activated B-cell (ABC) or non-GCB-like subtype based on gene expression signatures or immunohistochemical determination. The majority of PCNSL or PTL lymphoma derives from the non-GCB subtype. Recently, DLBCL patients with an immunohistochemical co-expression of c-MYC and BCL2 demonstrated inferior prognosis suggesting that concurrent expression of MYC/BCL2, termed double-protein-expression lymphoma (DPL), is a predictor of prognosis. Up to now there are no data, investigating the impact of DHL in patients with PCNSL or PTL.
Aims
We determined the frequency of DPL in a single center cohort of PCNSL or PTL and evaluated patients’ outcome in contrast to “standard” DLBCL not exhibiting concurrent expression of MYC/BCL2.
Methods
We evaluated retrospectively the appearance of DPL in 42 patients with CNS or testicular DLBCL, consecutively diagnosed and treated between 2004 and 2014 at our institution. To determine the double-hit score, immunohistochemistry for c-MYC and BCL2 was performed on diagnostic samples. Furthermore, the Choi algorithm was used to subclassify samples by cell-of-origin. On the basis of immunohistochemical c-MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group was defined by high expression of both MYC and BCL2 protein.
Results
Except for 3 samples, all patients were classified as non-GCB subtype. For 7 patients, no classification according to cell-of-origin could be performed. Of 42 primary extranodal DLBCL (PCNSL, n=28, PTL, n= 14), 29 patients were evaluable, 5 of them showed a double-hit score of 0, 11 patients had a DHS of 1, and 13 a DHS of 2, respectively. Using Kaplan-Meier curves and log-rank tests, probably due to small sample size, we could not demonstrate a significant different outcome for PCNSL or PTL patients with the non-GCB subtype as compared to the GCB subtype (p=0.74). However, we could clearly demonstrate a significant impaired outcome for patients with DHS of 2 (OS 61 versus 7 months, p=0.01) (Figure 1). Particularly, for patients with non-GCB subtype, we were able to further discriminate a subgroup of patients with an even worse clinical outcome to standard treatment (p=0.007).
Conclusion
: In this single center cohort, we could demonstrate a significant negative effect on OS for PCNSL or testicular large cell lymphoma patients co-expressing MYC and BCL2. We could further define a subgroup of patients within the non-GCB cohort demonstrating double hit positivity (DHS of 2) that is associated with a particular short survival. These non-GCB-, DHS positive DLBCL patients are candidates for novel therapeutic strategies.
Session topic: E-poster
Keyword(s): BCL2, Diffuse large B cell lymphoma, MYC
Type: Eposter Presentation
Background
Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal diffuse large B-cell lymphomas (DLBCLs) exhibiting a similar genetic signature and are characterised by an inferior response to current treatment regimens. DLBCL can be stratified by cell of origin (COO) derivation into the prognostically favorable germinal center B-cell (GCB)–like and the unfavorable activated B-cell (ABC) or non-GCB-like subtype based on gene expression signatures or immunohistochemical determination. The majority of PCNSL or PTL lymphoma derives from the non-GCB subtype. Recently, DLBCL patients with an immunohistochemical co-expression of c-MYC and BCL2 demonstrated inferior prognosis suggesting that concurrent expression of MYC/BCL2, termed double-protein-expression lymphoma (DPL), is a predictor of prognosis. Up to now there are no data, investigating the impact of DHL in patients with PCNSL or PTL.
Aims
We determined the frequency of DPL in a single center cohort of PCNSL or PTL and evaluated patients’ outcome in contrast to “standard” DLBCL not exhibiting concurrent expression of MYC/BCL2.
Methods
We evaluated retrospectively the appearance of DPL in 42 patients with CNS or testicular DLBCL, consecutively diagnosed and treated between 2004 and 2014 at our institution. To determine the double-hit score, immunohistochemistry for c-MYC and BCL2 was performed on diagnostic samples. Furthermore, the Choi algorithm was used to subclassify samples by cell-of-origin. On the basis of immunohistochemical c-MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group was defined by high expression of both MYC and BCL2 protein.
Results
Except for 3 samples, all patients were classified as non-GCB subtype. For 7 patients, no classification according to cell-of-origin could be performed. Of 42 primary extranodal DLBCL (PCNSL, n=28, PTL, n= 14), 29 patients were evaluable, 5 of them showed a double-hit score of 0, 11 patients had a DHS of 1, and 13 a DHS of 2, respectively. Using Kaplan-Meier curves and log-rank tests, probably due to small sample size, we could not demonstrate a significant different outcome for PCNSL or PTL patients with the non-GCB subtype as compared to the GCB subtype (p=0.74). However, we could clearly demonstrate a significant impaired outcome for patients with DHS of 2 (OS 61 versus 7 months, p=0.01) (Figure 1). Particularly, for patients with non-GCB subtype, we were able to further discriminate a subgroup of patients with an even worse clinical outcome to standard treatment (p=0.007).
Conclusion
: In this single center cohort, we could demonstrate a significant negative effect on OS for PCNSL or testicular large cell lymphoma patients co-expressing MYC and BCL2. We could further define a subgroup of patients within the non-GCB cohort demonstrating double hit positivity (DHS of 2) that is associated with a particular short survival. These non-GCB-, DHS positive DLBCL patients are candidates for novel therapeutic strategies.
Session topic: E-poster
Keyword(s): BCL2, Diffuse large B cell lymphoma, MYC
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