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Nishitha Reddy - One of the best experts on this subject based on the ideXlab platform.

  • differences in outcome of patients with syncytial variant hodgkin lymphoma compared with typical Nodular Sclerosis hodgkin lymphoma
    Therapeutic advances in hematology, 2017
    Co-Authors: Tarsheen K Sethi, Van T Nguyen, Shaoying Li, David S Morgan, John P Greer, Nishitha Reddy
    Abstract:

    BACKGROUND: Nodular Sclerosis Hodgkin lymphoma (NS-HL) is the most common subtype of HL and usually has a good prognosis. A variant of NS, the syncytial variant (SV) has well-established histopathologic features but little is known about its clinical behavior. Small case series have suggested that SV patients present with advanced disease and have a comparatively aggressive course. The objective of this study was to determine the clinical characteristics and outcome of SV patients. METHODS: A total of 167 adult patients with NS-HL including 43 patients with SV and 124 patients with typical NS (t-NS) were included in our analysis following institutional review board (IRB) approval. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. RESULTS: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) was the most frequent induction regimen administered in 91% of all patients. The rate of complete response (CR) in the SV group was 74% versus 87% in the t-NS group (p = 0.05). At 49 months follow up, the PFS was 17 months in the SV group and not reached in the t-NS group [p < 0.0001; hazard ratio (HR) = 3.695; 95% confidence interval (CI) = 3.0, 11.07]. The median OS was not reached in both groups (p = 0.32). CONCLUSIONS: Our results show that SV histology represents a poor risk group with lower CR rate and shorter PFS and this should be considered in the risk stratification of classical HL patients.

  • differences in outcome of patients with syncytial variant hodgkin lymphoma hl compared with typical Nodular Sclerosis hl
    Blood, 2015
    Co-Authors: Tarsheen K Sethi, Van T Nguyen, Shaoying Li, David S Morgan, John P Greer, Nishitha Reddy
    Abstract:

    Introduction: Syncytial variant of Nodular Sclerosis HL (SV) is a well-described distinct pathologic entity characterized by prominent aggregates of Hodgkin/Reed- Sternberg cells in nodules separated by fibrous collagen bands. Despite its well-known morphologic description, little is known regarding the clinical behavior of the SV. Previous reports suggest that patients with SV often presented with B symptoms and advanced stage disease, however, large series defining the clinical outcome have not been reported so far. We systematically studied the clinical features and outcome of patients with SV and further compared them with patients with typical Nodular Sclerosis HL (t-NS). Patients and Methods: 167 adult patients (pts.) with Nodular Sclerosis HL were included in our analysis following institutional IRB approval. Differences between the two groups (SV vs. t-NS) were analyzed using Chi- square and t -Student tests. Statistical significance was set at P Results: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. The median age at diagnosis was 31 yrs. (range: 18-75 yrs.) and 85 patients were male (51%). At diagnosis, 100% patients had an ECOG status of 0-1; 39 % had advanced stage disease (stage III and IV); and 48% had B symptoms. 23 % patients presented with bulky disease defined as a mass > 10 cm or a mediastinal mass >1/3 of thorax at T5-T6. 90% patients received ABVD as their initial treatment. The remaining were treated with Stanford V, MOPP or on a clinical trial. 37 % patients received radiation therapy. Furthermore, 63% patients with SV and relapsed disease were treated with high dose therapy followed by stem cell transplant (ASCT). In the SV vs. t-NS comparison, no statistically significant differences were observed between the two groups with regards to age, gender, stage at presentation, B symptoms, bulky disease or favorable features. The rate of complete response (CR) in the SV group was 74% vs. 87% in the t-NS group (P=0.05). Moreover, at a median follow up of 49 months, the median progression free survival (PFS) was inferior in the SV group (17.02 months) compared with the t-NS group (not reached) (P Discussion: In summary, our results suggest that SV was associated with a lower rate of complete response to standard ABVD chemotherapy +/- radiation and inferior PFS. Despite the high rate of relapse associated with SV, these patients can be salvaged with standard salvage regimens, ASCT or newer immunomodulatory agents and therefore not compromising OS. Our report suggests that patients with SV should be considered for novel combination immuno-chemotherapies to improve the rate of complete remission and subsequently avoid the need for ASCT. Disclosures Reddy:PCYC: Consultancy; ImmunoGen: Consultancy; Gilead: Other: Speaker; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding.

Tarsheen K Sethi - One of the best experts on this subject based on the ideXlab platform.

  • differences in outcome of patients with syncytial variant hodgkin lymphoma compared with typical Nodular Sclerosis hodgkin lymphoma
    Therapeutic advances in hematology, 2017
    Co-Authors: Tarsheen K Sethi, Van T Nguyen, Shaoying Li, David S Morgan, John P Greer, Nishitha Reddy
    Abstract:

    BACKGROUND: Nodular Sclerosis Hodgkin lymphoma (NS-HL) is the most common subtype of HL and usually has a good prognosis. A variant of NS, the syncytial variant (SV) has well-established histopathologic features but little is known about its clinical behavior. Small case series have suggested that SV patients present with advanced disease and have a comparatively aggressive course. The objective of this study was to determine the clinical characteristics and outcome of SV patients. METHODS: A total of 167 adult patients with NS-HL including 43 patients with SV and 124 patients with typical NS (t-NS) were included in our analysis following institutional review board (IRB) approval. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. RESULTS: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) was the most frequent induction regimen administered in 91% of all patients. The rate of complete response (CR) in the SV group was 74% versus 87% in the t-NS group (p = 0.05). At 49 months follow up, the PFS was 17 months in the SV group and not reached in the t-NS group [p < 0.0001; hazard ratio (HR) = 3.695; 95% confidence interval (CI) = 3.0, 11.07]. The median OS was not reached in both groups (p = 0.32). CONCLUSIONS: Our results show that SV histology represents a poor risk group with lower CR rate and shorter PFS and this should be considered in the risk stratification of classical HL patients.

  • differences in outcome of patients with syncytial variant hodgkin lymphoma hl compared with typical Nodular Sclerosis hl
    Blood, 2015
    Co-Authors: Tarsheen K Sethi, Van T Nguyen, Shaoying Li, David S Morgan, John P Greer, Nishitha Reddy
    Abstract:

    Introduction: Syncytial variant of Nodular Sclerosis HL (SV) is a well-described distinct pathologic entity characterized by prominent aggregates of Hodgkin/Reed- Sternberg cells in nodules separated by fibrous collagen bands. Despite its well-known morphologic description, little is known regarding the clinical behavior of the SV. Previous reports suggest that patients with SV often presented with B symptoms and advanced stage disease, however, large series defining the clinical outcome have not been reported so far. We systematically studied the clinical features and outcome of patients with SV and further compared them with patients with typical Nodular Sclerosis HL (t-NS). Patients and Methods: 167 adult patients (pts.) with Nodular Sclerosis HL were included in our analysis following institutional IRB approval. Differences between the two groups (SV vs. t-NS) were analyzed using Chi- square and t -Student tests. Statistical significance was set at P Results: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. The median age at diagnosis was 31 yrs. (range: 18-75 yrs.) and 85 patients were male (51%). At diagnosis, 100% patients had an ECOG status of 0-1; 39 % had advanced stage disease (stage III and IV); and 48% had B symptoms. 23 % patients presented with bulky disease defined as a mass > 10 cm or a mediastinal mass >1/3 of thorax at T5-T6. 90% patients received ABVD as their initial treatment. The remaining were treated with Stanford V, MOPP or on a clinical trial. 37 % patients received radiation therapy. Furthermore, 63% patients with SV and relapsed disease were treated with high dose therapy followed by stem cell transplant (ASCT). In the SV vs. t-NS comparison, no statistically significant differences were observed between the two groups with regards to age, gender, stage at presentation, B symptoms, bulky disease or favorable features. The rate of complete response (CR) in the SV group was 74% vs. 87% in the t-NS group (P=0.05). Moreover, at a median follow up of 49 months, the median progression free survival (PFS) was inferior in the SV group (17.02 months) compared with the t-NS group (not reached) (P Discussion: In summary, our results suggest that SV was associated with a lower rate of complete response to standard ABVD chemotherapy +/- radiation and inferior PFS. Despite the high rate of relapse associated with SV, these patients can be salvaged with standard salvage regimens, ASCT or newer immunomodulatory agents and therefore not compromising OS. Our report suggests that patients with SV should be considered for novel combination immuno-chemotherapies to improve the rate of complete remission and subsequently avoid the need for ASCT. Disclosures Reddy:PCYC: Consultancy; ImmunoGen: Consultancy; Gilead: Other: Speaker; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding.

W. C. Chan - One of the best experts on this subject based on the ideXlab platform.

  • the clonal relationship between Nodular Sclerosis hodgkin s disease with a clonal reed sternberg cell population and a subsequent b cell small noncleaved cell lymphoma
    Modern Pathology, 1998
    Co-Authors: T Ohno, G Wu, G Trenn, A Abouelella, H E Reis, W. C. Chan
    Abstract:

    : We evaluated the clonal relationship between a case of Nodular Sclerosis Hodgkin's disease (NSHD) and a small noncleaved cell (SNC) lymphoma that subsequently developed. Single Hodgkin and Reed-Sternberg (H-RS) cells were isolated from immunostained sections of the NSHD by micromanipulation, and the immunoglobulin heavy chain gene (IgH) complementarity determining region (CDR) III of the cells was amplified by the polymerase chain reaction (PCR). A clonal population of H-RS cells was found in the NSHD tumor. The nucleotide sequence of the clonal H-RS cells was compared with the clonal IgH CDRIII sequence from the SNC lymphoma. The two sequences were found to be unrelated. In addition, clone-specific primers and probes were designed from the two clonal IgH CDRIII sequences and used to investigate the presence of the respective clonal population in the NSHD tumor. The latter studies confirmed the presence of a major clonal H-RS cell population, as detected by the single cell assay, but cells corresponding to the SNC clone were not demonstrable by this highly sensitive technique. These findings suggest that the SNC arising in this case represents the development of the second neoplasm clonally unrelated to the preceding NSHD. They also support the recent findings that the H-RS cells in classical HD consist of a clonal population of B cells.

  • Phenotype, genotype and clonality of Reed-Sternberg cells in Nodular Sclerosis Hodgkin’s disease: results of a single-cell study
    British Journal of Haematology, 1996
    Co-Authors: Jan Delabie, Anne Tierens, Gavriil T, G Wu, Dennis D. Weisenburger, W. C. Chan
    Abstract:

    : The genotype and clonality of Reed-Sternberg (RS) cells in Hodgkin's disease (HD) has remained a controversial issue, largely due to the scarcity of RS cells in tissues and the limitations of the techniques used to resolve this issue. Southern hybridization and polymerase chain reaction (PCR) assays using DNA extracted from tissues can only document clonal gene rearrangements, but do not indicate which cellular population is responsible for such rearrangements. To overcome the limitations of these previous techniques for studying the genotype and clonality of RS cells, we analysed single RS cells with a single-cell PCR assay to detect immunoglobulin heavy chain gene (IgH) rearrangements and X-chromosome inactivation. Six cases of Nodular Sclerosis (NS) HD were studied. The RS cells displayed a B-cell phenotype in three cases and a null-cell phenotype in the other three cases. IgH rearrangements were detected in the RS cells of the three cases with a B-cell phenotype, but not in the other cases. In these three cases the IgH rearrangements in the RS cells were polyclonal, although a subpopulation of clonal RS cells was documented in one case. The finding that the RS cells with IgH rearrangements were not monoclonal was supported in one case by studying the pattern of X-chromosome inactivation in single RS cells by a single-cell human androgen receptor gene (HUMARA) PCR assay. Our results indicate that NSHD begins as a polyclonal process in which a clonal RS cell population may arise; and that the RS cells in a subset of NSHD show evidence of B-lineage differentiation.

  • phenotype genotype and clonality of reed sternberg cells in Nodular Sclerosis hodgkin s disease results of a single cell study
    British Journal of Haematology, 1996
    Co-Authors: Jan Delabie, Anne Tierens, G Wu, Dennis D. Weisenburger, T Gavriil, W. C. Chan
    Abstract:

    : The genotype and clonality of Reed-Sternberg (RS) cells in Hodgkin's disease (HD) has remained a controversial issue, largely due to the scarcity of RS cells in tissues and the limitations of the techniques used to resolve this issue. Southern hybridization and polymerase chain reaction (PCR) assays using DNA extracted from tissues can only document clonal gene rearrangements, but do not indicate which cellular population is responsible for such rearrangements. To overcome the limitations of these previous techniques for studying the genotype and clonality of RS cells, we analysed single RS cells with a single-cell PCR assay to detect immunoglobulin heavy chain gene (IgH) rearrangements and X-chromosome inactivation. Six cases of Nodular Sclerosis (NS) HD were studied. The RS cells displayed a B-cell phenotype in three cases and a null-cell phenotype in the other three cases. IgH rearrangements were detected in the RS cells of the three cases with a B-cell phenotype, but not in the other cases. In these three cases the IgH rearrangements in the RS cells were polyclonal, although a subpopulation of clonal RS cells was documented in one case. The finding that the RS cells with IgH rearrangements were not monoclonal was supported in one case by studying the pattern of X-chromosome inactivation in single RS cells by a single-cell human androgen receptor gene (HUMARA) PCR assay. Our results indicate that NSHD begins as a polyclonal process in which a clonal RS cell population may arise; and that the RS cells in a subset of NSHD show evidence of B-lineage differentiation.

Van T Nguyen - One of the best experts on this subject based on the ideXlab platform.

  • differences in outcome of patients with syncytial variant hodgkin lymphoma compared with typical Nodular Sclerosis hodgkin lymphoma
    Therapeutic advances in hematology, 2017
    Co-Authors: Tarsheen K Sethi, Van T Nguyen, Shaoying Li, David S Morgan, John P Greer, Nishitha Reddy
    Abstract:

    BACKGROUND: Nodular Sclerosis Hodgkin lymphoma (NS-HL) is the most common subtype of HL and usually has a good prognosis. A variant of NS, the syncytial variant (SV) has well-established histopathologic features but little is known about its clinical behavior. Small case series have suggested that SV patients present with advanced disease and have a comparatively aggressive course. The objective of this study was to determine the clinical characteristics and outcome of SV patients. METHODS: A total of 167 adult patients with NS-HL including 43 patients with SV and 124 patients with typical NS (t-NS) were included in our analysis following institutional review board (IRB) approval. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. RESULTS: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) was the most frequent induction regimen administered in 91% of all patients. The rate of complete response (CR) in the SV group was 74% versus 87% in the t-NS group (p = 0.05). At 49 months follow up, the PFS was 17 months in the SV group and not reached in the t-NS group [p < 0.0001; hazard ratio (HR) = 3.695; 95% confidence interval (CI) = 3.0, 11.07]. The median OS was not reached in both groups (p = 0.32). CONCLUSIONS: Our results show that SV histology represents a poor risk group with lower CR rate and shorter PFS and this should be considered in the risk stratification of classical HL patients.

  • differences in outcome of patients with syncytial variant hodgkin lymphoma hl compared with typical Nodular Sclerosis hl
    Blood, 2015
    Co-Authors: Tarsheen K Sethi, Van T Nguyen, Shaoying Li, David S Morgan, John P Greer, Nishitha Reddy
    Abstract:

    Introduction: Syncytial variant of Nodular Sclerosis HL (SV) is a well-described distinct pathologic entity characterized by prominent aggregates of Hodgkin/Reed- Sternberg cells in nodules separated by fibrous collagen bands. Despite its well-known morphologic description, little is known regarding the clinical behavior of the SV. Previous reports suggest that patients with SV often presented with B symptoms and advanced stage disease, however, large series defining the clinical outcome have not been reported so far. We systematically studied the clinical features and outcome of patients with SV and further compared them with patients with typical Nodular Sclerosis HL (t-NS). Patients and Methods: 167 adult patients (pts.) with Nodular Sclerosis HL were included in our analysis following institutional IRB approval. Differences between the two groups (SV vs. t-NS) were analyzed using Chi- square and t -Student tests. Statistical significance was set at P Results: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. The median age at diagnosis was 31 yrs. (range: 18-75 yrs.) and 85 patients were male (51%). At diagnosis, 100% patients had an ECOG status of 0-1; 39 % had advanced stage disease (stage III and IV); and 48% had B symptoms. 23 % patients presented with bulky disease defined as a mass > 10 cm or a mediastinal mass >1/3 of thorax at T5-T6. 90% patients received ABVD as their initial treatment. The remaining were treated with Stanford V, MOPP or on a clinical trial. 37 % patients received radiation therapy. Furthermore, 63% patients with SV and relapsed disease were treated with high dose therapy followed by stem cell transplant (ASCT). In the SV vs. t-NS comparison, no statistically significant differences were observed between the two groups with regards to age, gender, stage at presentation, B symptoms, bulky disease or favorable features. The rate of complete response (CR) in the SV group was 74% vs. 87% in the t-NS group (P=0.05). Moreover, at a median follow up of 49 months, the median progression free survival (PFS) was inferior in the SV group (17.02 months) compared with the t-NS group (not reached) (P Discussion: In summary, our results suggest that SV was associated with a lower rate of complete response to standard ABVD chemotherapy +/- radiation and inferior PFS. Despite the high rate of relapse associated with SV, these patients can be salvaged with standard salvage regimens, ASCT or newer immunomodulatory agents and therefore not compromising OS. Our report suggests that patients with SV should be considered for novel combination immuno-chemotherapies to improve the rate of complete remission and subsequently avoid the need for ASCT. Disclosures Reddy:PCYC: Consultancy; ImmunoGen: Consultancy; Gilead: Other: Speaker; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding.

Shaoying Li - One of the best experts on this subject based on the ideXlab platform.

  • differences in outcome of patients with syncytial variant hodgkin lymphoma compared with typical Nodular Sclerosis hodgkin lymphoma
    Therapeutic advances in hematology, 2017
    Co-Authors: Tarsheen K Sethi, Van T Nguyen, Shaoying Li, David S Morgan, John P Greer, Nishitha Reddy
    Abstract:

    BACKGROUND: Nodular Sclerosis Hodgkin lymphoma (NS-HL) is the most common subtype of HL and usually has a good prognosis. A variant of NS, the syncytial variant (SV) has well-established histopathologic features but little is known about its clinical behavior. Small case series have suggested that SV patients present with advanced disease and have a comparatively aggressive course. The objective of this study was to determine the clinical characteristics and outcome of SV patients. METHODS: A total of 167 adult patients with NS-HL including 43 patients with SV and 124 patients with typical NS (t-NS) were included in our analysis following institutional review board (IRB) approval. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. RESULTS: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) was the most frequent induction regimen administered in 91% of all patients. The rate of complete response (CR) in the SV group was 74% versus 87% in the t-NS group (p = 0.05). At 49 months follow up, the PFS was 17 months in the SV group and not reached in the t-NS group [p < 0.0001; hazard ratio (HR) = 3.695; 95% confidence interval (CI) = 3.0, 11.07]. The median OS was not reached in both groups (p = 0.32). CONCLUSIONS: Our results show that SV histology represents a poor risk group with lower CR rate and shorter PFS and this should be considered in the risk stratification of classical HL patients.

  • differences in outcome of patients with syncytial variant hodgkin lymphoma hl compared with typical Nodular Sclerosis hl
    Blood, 2015
    Co-Authors: Tarsheen K Sethi, Van T Nguyen, Shaoying Li, David S Morgan, John P Greer, Nishitha Reddy
    Abstract:

    Introduction: Syncytial variant of Nodular Sclerosis HL (SV) is a well-described distinct pathologic entity characterized by prominent aggregates of Hodgkin/Reed- Sternberg cells in nodules separated by fibrous collagen bands. Despite its well-known morphologic description, little is known regarding the clinical behavior of the SV. Previous reports suggest that patients with SV often presented with B symptoms and advanced stage disease, however, large series defining the clinical outcome have not been reported so far. We systematically studied the clinical features and outcome of patients with SV and further compared them with patients with typical Nodular Sclerosis HL (t-NS). Patients and Methods: 167 adult patients (pts.) with Nodular Sclerosis HL were included in our analysis following institutional IRB approval. Differences between the two groups (SV vs. t-NS) were analyzed using Chi- square and t -Student tests. Statistical significance was set at P Results: Of the 167 patients, 43 were confirmed as SV based on morphology and immunophenotype. The median age at diagnosis was 31 yrs. (range: 18-75 yrs.) and 85 patients were male (51%). At diagnosis, 100% patients had an ECOG status of 0-1; 39 % had advanced stage disease (stage III and IV); and 48% had B symptoms. 23 % patients presented with bulky disease defined as a mass > 10 cm or a mediastinal mass >1/3 of thorax at T5-T6. 90% patients received ABVD as their initial treatment. The remaining were treated with Stanford V, MOPP or on a clinical trial. 37 % patients received radiation therapy. Furthermore, 63% patients with SV and relapsed disease were treated with high dose therapy followed by stem cell transplant (ASCT). In the SV vs. t-NS comparison, no statistically significant differences were observed between the two groups with regards to age, gender, stage at presentation, B symptoms, bulky disease or favorable features. The rate of complete response (CR) in the SV group was 74% vs. 87% in the t-NS group (P=0.05). Moreover, at a median follow up of 49 months, the median progression free survival (PFS) was inferior in the SV group (17.02 months) compared with the t-NS group (not reached) (P Discussion: In summary, our results suggest that SV was associated with a lower rate of complete response to standard ABVD chemotherapy +/- radiation and inferior PFS. Despite the high rate of relapse associated with SV, these patients can be salvaged with standard salvage regimens, ASCT or newer immunomodulatory agents and therefore not compromising OS. Our report suggests that patients with SV should be considered for novel combination immuno-chemotherapies to improve the rate of complete remission and subsequently avoid the need for ASCT. Disclosures Reddy:PCYC: Consultancy; ImmunoGen: Consultancy; Gilead: Other: Speaker; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding.