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Analysis of Prognostic Factors in Patients with HIV-Associated Aggressive B-Cell Non-Hodgkin Lymphomas
Abstracts 528
529
Analysis of Prognostic Factors in Patients with HIV-Associated Aggressive B-Cell Non-Hodgkin Lymphomas
The role of pregnancy induced hormonal milieu in lymphoma progression
1
1
2
Blessy Mathew, Samir Dalia, Joseph Hall, Bijal Shah,1 Celeste Bello,1 Lubomir Sokol,1 Eduardo Sotomayor,1 Julio Chavez1
Netanel A. Horowitz,1 Noam Bettman,1 Ali Abed El Wahab,1 Tami Katz,1 Irit Avivi2 1
Hematology, Rambam Health Care Campus; 2Hematology, Tel Aviv
Sourasky Medical Center
1
Medicine/hematology oncology, Moffitt Cancer Center; 2Morsani
College of Medicine, University of South Florida
The occurrence of non-Hodgkin lymphomas (NHLs) is a significant challenge in HIV positive (HIV+) patients in the era of antiretroviral therapy (ART). Risk-stratification of these patients is vitally important. The study’s purpose was to analyze prognostic factors that could impact the survival of HIV+ patients with aggressive B-cell NHL. Patients with HIV associated aggressive B-cell NHL were identified between 1998 and 2012. Patients with indolent and primary central nervous system lymphoma were excluded. Clinical data including CD4 count, HIV viral load and opportunistic infections (OI) were analyzed using the Kaplan Meier method and statistical significance was assessed using the log-rank test. A total of 55 patients were included. The male: female ratio was 7/1. Median age was 43 years (29-65). The median time from HIV to NHL diagnosis was 29 months (0 e 284). Forty four (80%) had advanced stage (III/IV). The Eastern Cooperative Oncology Group performance status was 0-1 in 62%. The most common histologies were Diffuse Large B Cell Lymphoma 33 (62%) and Burkitt’s lymphoma 18 (33%). Bulky disease was present in 6 (11%), B symptoms in 18 (33%), elevated LDH in 20 (36%), and CD4 count < 100/mL at diagnosis in 11 (20%) patients. The mean Hb, SA and CD4 count were 12.1 g/dL, 3.73 g/dL and 224/uL. The median CD4 count at diagnosis was 180 (5 e 680). A serum albumin (SA) < 3.7 g/dL and Hb < 10 g/dl were present in 33% and 20.5% of patients, respectively. Twenty eight (51%) had ART at diagnosis. Sixty-one percent of patients received chemoimmunotherapy; the most common regimen was R-CHOP (50%). The cohort’s median OS was 29 months. The OS at 5 years was 42%. Poorer OS was associated with SA< 3.7 g/dl (median OS 11 m, HR: 3.15 [CI: 1.23-8.06], p¼0.017), IPI score 3(median OS 8 m, HR: 3.87 [CI: 1.53-9.73], p¼0.003), Hb < 10 g/dl (median OS 4 m, HR: 3.72 [CI 1.43-9.63], p¼0.012). The CD4 count and VL at diagnosis did not impact OS. A history of OIs had a trend toward worse OS (p¼0.056). Anemia and hypoalbuminemia are associated with poorer OS in HIV associated aggressive B-cell NHLs. These factors could be used as prognostic markers at NHL diagnosis in HIV+ patients. Future validation in larger studies will be needed.
S230
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Clinical Lymphoma, Myeloma & Leukemia June 2015
Introduction: Lymphoma is the most common hematological cancer reported during pregnancy. Recent data suggest that unlike lymphoma occurring outside of pregnancy, pregnancy-associated lymphoma is characterized by an excessive involvement of reproductive organs, advanced disease stage at diagnosis and an aggressive course, potentially leading to a high death rate of mothers. Objective: To determined the role of estrogen and progesterone in lymphoma progression in vitro. Methods: Several human lymphoma cell lines were analyzed by FACS for expression of estrogen (a & b) and progesterone receptors. Human breast cancer cell line Mfc-7 was used as a positive control. CFSE-stained BL2 cells, were treated with E2 (25mM & 100mM) for 24h & 48h. Cells were harvested and analyzed by FACS for determining cell proliferation. Ramos cells, were treated with E2 (5-25mM) for 72h. Cells were harvested and stained with Annexin-PI for determining live/ necrotic/apoptotic cell proportion. BL2 cells, either seeded alone or co-cultured with HK cells for 24h, were treated with E2 (25mM & 100mM) for 24h. Cells were analyzed for determining live/necrotic/ apoptotic cell proportion. Results: Lymphoma cell lines express both estrogen receptors but not progesterone receptor. Estrogen treated lymphoma cells demonstrated reduced proliferation rate in a concentration dependent manner. Furthermore, apoptosis and necrosis of lymphoma cells were significantly increased with concentration-dependent estrogen treatment. Progesterone had no effect on lymphoma cells proliferation, apoptosis or necrosis. The negative effect of estrogen on lymphoma cells was reversed in the presence of lymph node stromal cells. Estrogen treated lymphoma cells that were cultured on lymph node stromal cells demonstrated significantly less apoptosis and necrosis rates relative to non cultured cells. Conclusion: Lymphoma cells express estrogen but not progesterone receptors. Estrogen induces lymphoma cells necrosis and apoptosis and reduces proliferation. Lymph node stromal cells protect lymphoma cells from estrogen mediated effects. The direct effect of estrogen on lymphoma cells does not support lymphoma progression and other mechanisms should be seek to explain the aggressive nature of lymphoma diagnosed during pregnancy.
529
Analysis of Prognostic Factors in Patients with HIV-Associated Aggressive B-Cell Non-Hodgkin Lymphomas
The role of pregnancy induced hormonal milieu in lymphoma progression
1
1
2
Blessy Mathew, Samir Dalia, Joseph Hall, Bijal Shah,1 Celeste Bello,1 Lubomir Sokol,1 Eduardo Sotomayor,1 Julio Chavez1
Netanel A. Horowitz,1 Noam Bettman,1 Ali Abed El Wahab,1 Tami Katz,1 Irit Avivi2 1
Hematology, Rambam Health Care Campus; 2Hematology, Tel Aviv
Sourasky Medical Center
1
Medicine/hematology oncology, Moffitt Cancer Center; 2Morsani
College of Medicine, University of South Florida
The occurrence of non-Hodgkin lymphomas (NHLs) is a significant challenge in HIV positive (HIV+) patients in the era of antiretroviral therapy (ART). Risk-stratification of these patients is vitally important. The study’s purpose was to analyze prognostic factors that could impact the survival of HIV+ patients with aggressive B-cell NHL. Patients with HIV associated aggressive B-cell NHL were identified between 1998 and 2012. Patients with indolent and primary central nervous system lymphoma were excluded. Clinical data including CD4 count, HIV viral load and opportunistic infections (OI) were analyzed using the Kaplan Meier method and statistical significance was assessed using the log-rank test. A total of 55 patients were included. The male: female ratio was 7/1. Median age was 43 years (29-65). The median time from HIV to NHL diagnosis was 29 months (0 e 284). Forty four (80%) had advanced stage (III/IV). The Eastern Cooperative Oncology Group performance status was 0-1 in 62%. The most common histologies were Diffuse Large B Cell Lymphoma 33 (62%) and Burkitt’s lymphoma 18 (33%). Bulky disease was present in 6 (11%), B symptoms in 18 (33%), elevated LDH in 20 (36%), and CD4 count < 100/mL at diagnosis in 11 (20%) patients. The mean Hb, SA and CD4 count were 12.1 g/dL, 3.73 g/dL and 224/uL. The median CD4 count at diagnosis was 180 (5 e 680). A serum albumin (SA) < 3.7 g/dL and Hb < 10 g/dl were present in 33% and 20.5% of patients, respectively. Twenty eight (51%) had ART at diagnosis. Sixty-one percent of patients received chemoimmunotherapy; the most common regimen was R-CHOP (50%). The cohort’s median OS was 29 months. The OS at 5 years was 42%. Poorer OS was associated with SA< 3.7 g/dl (median OS 11 m, HR: 3.15 [CI: 1.23-8.06], p¼0.017), IPI score 3(median OS 8 m, HR: 3.87 [CI: 1.53-9.73], p¼0.003), Hb < 10 g/dl (median OS 4 m, HR: 3.72 [CI 1.43-9.63], p¼0.012). The CD4 count and VL at diagnosis did not impact OS. A history of OIs had a trend toward worse OS (p¼0.056). Anemia and hypoalbuminemia are associated with poorer OS in HIV associated aggressive B-cell NHLs. These factors could be used as prognostic markers at NHL diagnosis in HIV+ patients. Future validation in larger studies will be needed.
S230
-
Clinical Lymphoma, Myeloma & Leukemia June 2015
Introduction: Lymphoma is the most common hematological cancer reported during pregnancy. Recent data suggest that unlike lymphoma occurring outside of pregnancy, pregnancy-associated lymphoma is characterized by an excessive involvement of reproductive organs, advanced disease stage at diagnosis and an aggressive course, potentially leading to a high death rate of mothers. Objective: To determined the role of estrogen and progesterone in lymphoma progression in vitro. Methods: Several human lymphoma cell lines were analyzed by FACS for expression of estrogen (a & b) and progesterone receptors. Human breast cancer cell line Mfc-7 was used as a positive control. CFSE-stained BL2 cells, were treated with E2 (25mM & 100mM) for 24h & 48h. Cells were harvested and analyzed by FACS for determining cell proliferation. Ramos cells, were treated with E2 (5-25mM) for 72h. Cells were harvested and stained with Annexin-PI for determining live/ necrotic/apoptotic cell proportion. BL2 cells, either seeded alone or co-cultured with HK cells for 24h, were treated with E2 (25mM & 100mM) for 24h. Cells were analyzed for determining live/necrotic/ apoptotic cell proportion. Results: Lymphoma cell lines express both estrogen receptors but not progesterone receptor. Estrogen treated lymphoma cells demonstrated reduced proliferation rate in a concentration dependent manner. Furthermore, apoptosis and necrosis of lymphoma cells were significantly increased with concentration-dependent estrogen treatment. Progesterone had no effect on lymphoma cells proliferation, apoptosis or necrosis. The negative effect of estrogen on lymphoma cells was reversed in the presence of lymph node stromal cells. Estrogen treated lymphoma cells that were cultured on lymph node stromal cells demonstrated significantly less apoptosis and necrosis rates relative to non cultured cells. Conclusion: Lymphoma cells express estrogen but not progesterone receptors. Estrogen induces lymphoma cells necrosis and apoptosis and reduces proliferation. Lymph node stromal cells protect lymphoma cells from estrogen mediated effects. The direct effect of estrogen on lymphoma cells does not support lymphoma progression and other mechanisms should be seek to explain the aggressive nature of lymphoma diagnosed during pregnancy.