PROGNOSTIC IMPACT, PHENOTYPIC AND MOLECULAR CHARACTERIZATION OF CONCORDANT AND DISCORDANT BONE MARROW INVOLVEMENT IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA
(Abstract release date: 05/19/16)
EHA Library. Alcoceba M. 06/09/16; 132930; E1381
Dr. Miguel Alcoceba
Contributions
Contributions
Abstract
Abstract: E1381
Type: Eposter Presentation
Background
In the rituximab era, the biology and prognostic influence of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) has been hardly studied.
Aims
In this retrospective study, we aimed to investigate: i) the prognostic influence of concordant (DLBCL histology) and discordant (low-grade lymphoma) BM infiltration in patients with DLBCL; ii) the correlation of cell of origin (COO) of the DLBCL and the type of BM infiltration; iii) the clonal relationship between BM and lymph node (LN) tumor cells in the discordant cases; and iiii) the incidence of TP53, CMYC, BCL2, BCL6 genetic alterations in the cases with BM infiltration.
Methods
All patients with histological diagnosis of DLBCL in our center from January 1, 1999 were included. Survival analysis was performed only in the patients treated with rituximab (R) plus curative chemotherapy. All BM samples were reviewed and classified as concordant or discordant infiltration according to histological criteria. COO was assessed by Hans method. Phenotypic description of discordant marrows was performed by flow cytometry (FCM). Clonal relationship between BM and lymph node (LN) was performed by VDJ sequencing according to BIOMED-2 protocol. TP53, CMYC, BCL2, BCL6 were analyzed using fluorescence in situ hybridation (FISH).
Results
From 232 patients included in the study, 36 (15%) had concordant histological BM infiltration and 22 (9%) discordant. Phenotypic characterization of the discordant cases, including those detected only by FCM, was heterogeneous, representing different types of indolent B-cell lymphomas:CLL (7), FL (8), MZL (4) LPL (2), DLBCL (23), Composite (2), Not specified (8). Clonality studies from the 15 evaluable discordant cases, confirmed the same clone in both BM and lymphadenopathy in 12 patients (80%); we observed that the most frequent VH segment was VH4.34, only seen in patients with non-germinal center (non-GCB) COO phenotype. FISH analysis revealed a high rate of genetic aberrations, particularly in the concordant group of patients, as shown in table 2. BCL2 translocations stood out in the GC phenotype group, while CMYC gains concentrated among those with discordant BM infiltration. TP53 deletions, were mostly seen in the concordant non-GC group of patients. Survival analysis were conducted in the 189 patients treated with R plus curative chemotherapy. With a median follow up of 58 months, 5-year PFS was significantly worse in patients with concordant BM infiltration (30,4%) compared with those with discordant (64.8%, p=0.004) or without infiltration (67.8%, p=0.001). This negative influence of concordant BM involvement on PFS was independent of IPI in the multivariate analysis (HR = 2.25, 95% CI 1.2 to 4.3, p = 0.01). IPI was the only variable with independent influence on OS. By combining COO and type of BM infiltration, we observed that patients with discordant BM and non-GC COO were a group not previously described with decreased PFS (41.9% at 5 years) as compared with the non-infiltrated GCB group (78.3%, p=0.007) and the non-infiltrated non-GCB group (73%, p=0.05) (Figure1).
Conclusion
Our results confirm the adverse prognosis of concordant BM infiltration but reveal that the type of BM infiltration could be more informative when combined with DLBCL COO and FISH analysis, allowing better prognostic stratification of patients. Among discordant cases we find a high rate of clonal relationship between the two different histologies, which suggest that most cases are histologic transformations from a low-grade lymphoma. Larger prospective studies are needed to confirm these results.
Session topic: E-poster
Keyword(s): Bone Marrow
Type: Eposter Presentation
Background
In the rituximab era, the biology and prognostic influence of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) has been hardly studied.
Aims
In this retrospective study, we aimed to investigate: i) the prognostic influence of concordant (DLBCL histology) and discordant (low-grade lymphoma) BM infiltration in patients with DLBCL; ii) the correlation of cell of origin (COO) of the DLBCL and the type of BM infiltration; iii) the clonal relationship between BM and lymph node (LN) tumor cells in the discordant cases; and iiii) the incidence of TP53, CMYC, BCL2, BCL6 genetic alterations in the cases with BM infiltration.
Methods
All patients with histological diagnosis of DLBCL in our center from January 1, 1999 were included. Survival analysis was performed only in the patients treated with rituximab (R) plus curative chemotherapy. All BM samples were reviewed and classified as concordant or discordant infiltration according to histological criteria. COO was assessed by Hans method. Phenotypic description of discordant marrows was performed by flow cytometry (FCM). Clonal relationship between BM and lymph node (LN) was performed by VDJ sequencing according to BIOMED-2 protocol. TP53, CMYC, BCL2, BCL6 were analyzed using fluorescence in situ hybridation (FISH).
Results
From 232 patients included in the study, 36 (15%) had concordant histological BM infiltration and 22 (9%) discordant. Phenotypic characterization of the discordant cases, including those detected only by FCM, was heterogeneous, representing different types of indolent B-cell lymphomas:CLL (7), FL (8), MZL (4) LPL (2), DLBCL (23), Composite (2), Not specified (8). Clonality studies from the 15 evaluable discordant cases, confirmed the same clone in both BM and lymphadenopathy in 12 patients (80%); we observed that the most frequent VH segment was VH4.34, only seen in patients with non-germinal center (non-GCB) COO phenotype. FISH analysis revealed a high rate of genetic aberrations, particularly in the concordant group of patients, as shown in table 2. BCL2 translocations stood out in the GC phenotype group, while CMYC gains concentrated among those with discordant BM infiltration. TP53 deletions, were mostly seen in the concordant non-GC group of patients. Survival analysis were conducted in the 189 patients treated with R plus curative chemotherapy. With a median follow up of 58 months, 5-year PFS was significantly worse in patients with concordant BM infiltration (30,4%) compared with those with discordant (64.8%, p=0.004) or without infiltration (67.8%, p=0.001). This negative influence of concordant BM involvement on PFS was independent of IPI in the multivariate analysis (HR = 2.25, 95% CI 1.2 to 4.3, p = 0.01). IPI was the only variable with independent influence on OS. By combining COO and type of BM infiltration, we observed that patients with discordant BM and non-GC COO were a group not previously described with decreased PFS (41.9% at 5 years) as compared with the non-infiltrated GCB group (78.3%, p=0.007) and the non-infiltrated non-GCB group (73%, p=0.05) (Figure1).
Conclusion
Our results confirm the adverse prognosis of concordant BM infiltration but reveal that the type of BM infiltration could be more informative when combined with DLBCL COO and FISH analysis, allowing better prognostic stratification of patients. Among discordant cases we find a high rate of clonal relationship between the two different histologies, which suggest that most cases are histologic transformations from a low-grade lymphoma. Larger prospective studies are needed to confirm these results.
Session topic: E-poster
Keyword(s): Bone Marrow
Abstract: E1381
Type: Eposter Presentation
Background
In the rituximab era, the biology and prognostic influence of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) has been hardly studied.
Aims
In this retrospective study, we aimed to investigate: i) the prognostic influence of concordant (DLBCL histology) and discordant (low-grade lymphoma) BM infiltration in patients with DLBCL; ii) the correlation of cell of origin (COO) of the DLBCL and the type of BM infiltration; iii) the clonal relationship between BM and lymph node (LN) tumor cells in the discordant cases; and iiii) the incidence of TP53, CMYC, BCL2, BCL6 genetic alterations in the cases with BM infiltration.
Methods
All patients with histological diagnosis of DLBCL in our center from January 1, 1999 were included. Survival analysis was performed only in the patients treated with rituximab (R) plus curative chemotherapy. All BM samples were reviewed and classified as concordant or discordant infiltration according to histological criteria. COO was assessed by Hans method. Phenotypic description of discordant marrows was performed by flow cytometry (FCM). Clonal relationship between BM and lymph node (LN) was performed by VDJ sequencing according to BIOMED-2 protocol. TP53, CMYC, BCL2, BCL6 were analyzed using fluorescence in situ hybridation (FISH).
Results
From 232 patients included in the study, 36 (15%) had concordant histological BM infiltration and 22 (9%) discordant. Phenotypic characterization of the discordant cases, including those detected only by FCM, was heterogeneous, representing different types of indolent B-cell lymphomas:CLL (7), FL (8), MZL (4) LPL (2), DLBCL (23), Composite (2), Not specified (8). Clonality studies from the 15 evaluable discordant cases, confirmed the same clone in both BM and lymphadenopathy in 12 patients (80%); we observed that the most frequent VH segment was VH4.34, only seen in patients with non-germinal center (non-GCB) COO phenotype. FISH analysis revealed a high rate of genetic aberrations, particularly in the concordant group of patients, as shown in table 2. BCL2 translocations stood out in the GC phenotype group, while CMYC gains concentrated among those with discordant BM infiltration. TP53 deletions, were mostly seen in the concordant non-GC group of patients. Survival analysis were conducted in the 189 patients treated with R plus curative chemotherapy. With a median follow up of 58 months, 5-year PFS was significantly worse in patients with concordant BM infiltration (30,4%) compared with those with discordant (64.8%, p=0.004) or without infiltration (67.8%, p=0.001). This negative influence of concordant BM involvement on PFS was independent of IPI in the multivariate analysis (HR = 2.25, 95% CI 1.2 to 4.3, p = 0.01). IPI was the only variable with independent influence on OS. By combining COO and type of BM infiltration, we observed that patients with discordant BM and non-GC COO were a group not previously described with decreased PFS (41.9% at 5 years) as compared with the non-infiltrated GCB group (78.3%, p=0.007) and the non-infiltrated non-GCB group (73%, p=0.05) (Figure1).
Conclusion
Our results confirm the adverse prognosis of concordant BM infiltration but reveal that the type of BM infiltration could be more informative when combined with DLBCL COO and FISH analysis, allowing better prognostic stratification of patients. Among discordant cases we find a high rate of clonal relationship between the two different histologies, which suggest that most cases are histologic transformations from a low-grade lymphoma. Larger prospective studies are needed to confirm these results.
Session topic: E-poster
Keyword(s): Bone Marrow
Type: Eposter Presentation
Background
In the rituximab era, the biology and prognostic influence of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) has been hardly studied.
Aims
In this retrospective study, we aimed to investigate: i) the prognostic influence of concordant (DLBCL histology) and discordant (low-grade lymphoma) BM infiltration in patients with DLBCL; ii) the correlation of cell of origin (COO) of the DLBCL and the type of BM infiltration; iii) the clonal relationship between BM and lymph node (LN) tumor cells in the discordant cases; and iiii) the incidence of TP53, CMYC, BCL2, BCL6 genetic alterations in the cases with BM infiltration.
Methods
All patients with histological diagnosis of DLBCL in our center from January 1, 1999 were included. Survival analysis was performed only in the patients treated with rituximab (R) plus curative chemotherapy. All BM samples were reviewed and classified as concordant or discordant infiltration according to histological criteria. COO was assessed by Hans method. Phenotypic description of discordant marrows was performed by flow cytometry (FCM). Clonal relationship between BM and lymph node (LN) was performed by VDJ sequencing according to BIOMED-2 protocol. TP53, CMYC, BCL2, BCL6 were analyzed using fluorescence in situ hybridation (FISH).
Results
From 232 patients included in the study, 36 (15%) had concordant histological BM infiltration and 22 (9%) discordant. Phenotypic characterization of the discordant cases, including those detected only by FCM, was heterogeneous, representing different types of indolent B-cell lymphomas:CLL (7), FL (8), MZL (4) LPL (2), DLBCL (23), Composite (2), Not specified (8). Clonality studies from the 15 evaluable discordant cases, confirmed the same clone in both BM and lymphadenopathy in 12 patients (80%); we observed that the most frequent VH segment was VH4.34, only seen in patients with non-germinal center (non-GCB) COO phenotype. FISH analysis revealed a high rate of genetic aberrations, particularly in the concordant group of patients, as shown in table 2. BCL2 translocations stood out in the GC phenotype group, while CMYC gains concentrated among those with discordant BM infiltration. TP53 deletions, were mostly seen in the concordant non-GC group of patients. Survival analysis were conducted in the 189 patients treated with R plus curative chemotherapy. With a median follow up of 58 months, 5-year PFS was significantly worse in patients with concordant BM infiltration (30,4%) compared with those with discordant (64.8%, p=0.004) or without infiltration (67.8%, p=0.001). This negative influence of concordant BM involvement on PFS was independent of IPI in the multivariate analysis (HR = 2.25, 95% CI 1.2 to 4.3, p = 0.01). IPI was the only variable with independent influence on OS. By combining COO and type of BM infiltration, we observed that patients with discordant BM and non-GC COO were a group not previously described with decreased PFS (41.9% at 5 years) as compared with the non-infiltrated GCB group (78.3%, p=0.007) and the non-infiltrated non-GCB group (73%, p=0.05) (Figure1).
Conclusion
Our results confirm the adverse prognosis of concordant BM infiltration but reveal that the type of BM infiltration could be more informative when combined with DLBCL COO and FISH analysis, allowing better prognostic stratification of patients. Among discordant cases we find a high rate of clonal relationship between the two different histologies, which suggest that most cases are histologic transformations from a low-grade lymphoma. Larger prospective studies are needed to confirm these results.
Session topic: E-poster
Keyword(s): Bone Marrow
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