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  • 1
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1756-1756
    Abstract: Although immunosuppression has long been recognized in classical Hodgkin lymphoma (cHL), the underlying basis for the lack of an effective immune response against the tumor remains unclear. Increased frequencies of regulatory CD4+ T lymphocytes in the tumor microenvironment and peripheral blood have been proposed as one of the mechanisms for this anergic state. However, little is known about the disbalance between regulatory and effector CD4+ subpopulations and cytokines in the peripheral blood of cHL patients and how treatment can modify this regulatory/effector ratio. In this study, we analyzed the regulatory and effector CD4+ subpopulations together with pro and anti-inflammatory cytokines in peripheral blood of cHL patients and the impact of treatment on these cells and cytokines. Material and Methods This is an open multicenter study and, so far, we included 54 patients from December 2009 to July 2013. Thirty-four patients have completed therapy on July 2012 and were included in this study. Blood was drawn at diagnosis and after completion of treatment (1 to 4 months). Nineteen healthy blood donors volunteers were recruited as controls. Quantification of regulatory and effector T lymphocytes was done by flow cytometry using CD3, CD8, CD4, CD25, Foxp3, CTLA4, GITR and interleukin-17 (IL17) antibodies. Ten cytokines were studied: IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, sIL-2Rα, TNF-α, IFN-γ, and VEGF. Cytokine levels were determined by multiplexed immunoassay system. All these parameters were correlated to phenotypic and clinical parameters in uni- and multivariate models pre and post-treatment. In this study, only cHL patients whose histology could be confirmed and EBV association established were studied. All patients were HIV negative and received ABVD chemotherapy protocol and radiotherapy if necessary. Results From the 34 cHL patients recruited for this study, 17 (50%) were male, 16 (47%) had Epstein-Barr virus (EBV) related cHL, 27 (79%) patients presented with B symptoms and 18 (53%) patients had advanced diseases at diagnosis. Results of subsets of CD4+ T cells and cytokines are summarized in the following table: After treatment, the percentage of regulatory CD4+CD25highFoxP3+ and effector CD4+IL17+ T lymphocytes were not different from diagnosis (0.9 vs 0.4, p=0.45; 0.6 vs 0.9, p=0.52; respectively) and from controls (0.9 vs 0.3, p=0.22; 0.6 vs 0.7, p=0.84; respectively). Interestingly, increased CD4+CD25highFoxP3+ T lymphocytes were correlated with advanced disease at diagnosis (p=0.03) and an erythrocyte sedimentation rate (ESR) 〉 30 mmHg (p=0.01). Additionally, we found a negative correlation between soluble IL-2Rα and CD4+GITR+ (p=0.02) and CD4+FOXP3+ (p=0.02). Conclusions In this study, we showed that, after treatment, there was a decrease of some subsets of CD4+ T cells with regulatory phenotype, together with a decrease of IL-6, IL-10 and sIL-2Rα. Understanding cHL associated immunosuppression and the immune reconstitution after treatment maybe the key to develop new treatment strategies, designed to manipulate regulatory activity. Further studies investigating these CD4+ T lymphocytes subpopulations with functional assays are warranted. Given that the incidence of EBV-related cHL, disease presentation and severity are different in developing countries than in developed ones, we emphasize the importance of this ongoing Brazilian multicenter project. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 2
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4777-4777
    Abstract: Abstract 4777 Understanding the mechanisms of how tumor microenvironment of classical Hodgkin lymphoma (cHL) fosters immune privilege and survival of Hodgkin-Reed-Sternberg (HRS) cells is crucial for the development of new biomarkers and therapy strategies. Recently, infiltrating regulatory T CD4+CD25+FOXP3+ lymphocytes (Tregs) and tumor-associated macrophages CD68+ (TAMs) have been shown to play a role in HRS immune evasion, disease progression and survival. However, data arising from studies of different populations of cHL patients are conflicting. Purpose: In this study, we evaluated the importance of infiltrating Tregs and TAMs in a subset of 130 cHL patients treated in public hospitals in southeast Brazil and correlated these findings with Epstein-Barr virus (EBV) presence in HRS cells. Material and Methods: Tissue microarrays were constructed using diagnostic biopsies available in 130 patients and stained with CD4, CD8, CD25, FOXP3, CD15, CD30, CD68 e LMP1. Quantification of TAMs and Tregs was performed using automated slide scanning and image analysis (Aperio ScanScope XT Slide Scanner and Aperio ImageScope Software with Aperio Positive Pixel Count Sample Macro algorithm). Immunohistochemical scoring ranged from 1 to 4 for the antibodies tested, with higher scores indicating a greater proportion of positive cells. For Tregs and TAMs quantification, score 1 was considered negative (≤ 25 % of Tregs or TAMs) and scores 2, 3, and 4 (more than 25 % of positive cells) were considered positive. All patients underwent similar chemotherapy protocols. For the present study, only cHL patients whose histology could be confirmed and EBV-association established were studied. Results: From the 130 cHL patients selected for this study, 56 (43%) were classified as EBV related and 74 (57%) EBV non-related cHL. The expression of Tregs (CD4/CD25/FOXP3) was more common in the EBV related cHL group (p=0.02). TAMs did not correlate with EBV presence in HRS cells. Response to treatment, either complete response or partial response, and relapse rate were independent of Tregs and TAMs quantification and EBV status. Increased Tregs and TAMs in the tumor microenvironment did not influence event-free survival (EFS) and overall survival (OS). For further analysis, we stratified our patients into 4 groups, according to Tregs and TAMs quantification and EBV status and we still did not find any difference on EFS and OS. Additionally, stratified survival analysis according to age, stage and IPS-risk group did not identify any impact of Tregs and TAMs quantification on EFS and OS. Conclusion: This study demonstrates that increased Tregs and TAMs in the tumor microenvironment of cHL patients neither correlate with treatment response nor survival. Additionally, increased Tregs correlated with EBV presence in HRS cells. It is well known that the incidence of EBV-related cHL in developing countries is different from that in developed ones, as well as the severity of the disease at presentation, with advanced disease being more common at diagnosis. Our results, although different from those recently published, probably reflect the reality of the Brazilian population enrolled in the public health system, highlighting the importance of studying the same disease and their potential biomarkers within different populations. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4236-4236
    Abstract: Classical Hodgkin lymphoma (cHL) is one of the most curable cancers, with cure rates ranging from 65-90%, depending on different risk factors. These factors include both clinical (international prognostic score, IPS) and biological markers (tumor associated macrophages, for example). However, most biological biomarkers are not available in a routine basis and IPS does not offer risk stratification for patients diagnosed with early stage cHL. Recently, Porrata et al described the peripheral lymphocyte/monocyte ratio (LMR) as a strong prognostic factor in patients with cHL. In his study, an LMR of less than 1.1 was related with poor outcome. Objectives To assess the role of lymphocyte/monocyte ratio at diagnosis in predicting outcome and survival in cHL patients in Brazil. Patient and Methods This is a retrospective multicenter study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of cHL, diagnosed between April 1986 to January 2013, with clinical, epidemiological and laboratorial parameters available after a thorough chart review were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Advanced stage disease was defined as stage I or II with B symptoms and/or bulky disease and stage III or IV. Patients with conflicted data or loss of follow up were excluded from the analysis. Results A total of 570 patients were diagnosed with cHL in this period. However, 303 patients were selected for this study. Nodular sclerosis subtype was diagnosed in 207 (68%) of all patients. Median age at diagnosis was 30 years old (raging from 12-78), with a 0,9:1 Female:Male ratio. The majority (210, 69%) presented with advanced disease. ABVD chemotherapy protocol was the initial therapy in 91% of patients, MOPP/ABV in 8% and 1% of patients received only radiotherapy. For early-stage disease, a median of 6 cycles was delivered and 8 cycles were given for patients with advanced disease. Consolidation radiotherapy was done in 175 (58%) of all patients after chemotherapy. Overall responses were: CR in 90,7% (n=274), Partial response/Refractory disease in 8,9% (n=27); one patient died due to treatment-related toxicity. CR rates were 97,8% in early stage disease and 89,4% in advanced stage (p=0.07). Overall Survival (OS) for the entire group was 95% in 5 years (CI95% 73-83%), with a progression free survival (PFS) of 78% (CI95% 91-97%). A Lymphocyte/Monocyte ratio (LMR) less than 1.1 was not predictive of survival in our patients, neither PFS (84% vs 78%, p=0.30) nor OS (95% vs 96%, p=0.48). However, absolute lymphocyte count (ALC) greater than 1000 cells/mL at diagnosis was related to a better OS (97% vs 88%, p=0.003). Conclusions Although cHL is highly curable, it is an unmet medical need to better stratify these patients at diagnosis, especially with simple and straightforward prognostic factors, such as absolute lymphocyte count at diagnosis. In our study, LMR less than 1.1 was not associated with survival, as recently pointed by Porrata et al., but an ALC greater than 1000 cells/mL was related to better overall survival. It is well known that the incidence of EBV-related cHL, disease presentation and severity are different in developing countries than in developed ones; therefore, prognostic factors may differ from different studied populations, highlighting the importance of our results. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4780-4780
    Abstract: Abstract 4780 Introduction: Epstein-Barr virus (EBV) can be found latently infecting Reed-Sternberg (RS) malignant cells in approximately 50% of classical Hodgkin lymphoma (cHL) patients in Brazil. EBV signaling leads to a disbalance between effector and regulatory CD4 T lymphocytes in the tumor microenvironment, promoting the immune evasion of RS malignant cells. However, little is known about these lymphocytes subpopulations in the peripheral blood of patients with cHL and how treatment can modify this regulatory/effector ratio. In this study, we analyzed the regulatory and effector CD4+ subpopulations in peripheral blood in patients with EBV related and non-related cHL and the impact of treatment on these cells. Material and Methods: This is an open multicentric study and, so far, we included 35 patients from December 2009 to December 2011. Blood was drawn at diagnosis and after completion of treatment (1 to 4 months). Eighteen healthy blood donors volunteers were recruited as controls. Quantification of regulatory and effector T lymphocytes was done by flow cytometry using CD3, CD8, CD4, CD25, Foxp3, GITR, CD127 and interleukin-17 (IL17) antibodies and correlated to phenotypic and clinical parameters in uni- and multivariate models pre and post-treatment. In this study, only cHL patients whose histology could be confirmed and EBV association established were studied. All patients were HIV negative and received ABVD chemotherapy protocol and radiotherapy if necessary. Results: From the 35 cHL patients, 17 were EBV related and 18 EBV non-related. The percentage of CD4+CD25highFoxP3+ and CD4+GITR+ at diagnosis was significantly different from healthy controls (median 1.04 vs 0.26, p=0.02; 4.2 vs 2.2, p=0.003; respectively). CD4+CD127+ T lymphocytes were not different from controls (p=0.3). Additionally, CD4+ T lymphocytes with effector phenotype (CD4+IL17+) were significantly increased in cHL patients compared with controls (0.42 vs 0.13, p 〈 0.001). When we compared pre-treatment values of regulatory and effector CD4+ T lymphocytes with post-treatment values, we did not find any statistical difference. Interestingly, post-treatment values were not statistically different from healthy controls. There was no difference on regulatory and effector CD4+ T lymphocytes in the EBV related and non-related cHL patients. Regarding patient's baseline characteristics, patients with advanced disease and B symptoms presented with increased CD4+CD25highFoxP3+ and CD4+GITR+ T lymphocytes (p=0.03 and p=0.01, respectively). Conclusions: Our results demonstrate that patients with cHL presented with increased CD4+CD25highFoxP3+, CD4+GITR+ and CD4+IL17+ at diagnosis compared with healthy controls. Also, treatment had no impact on these CD4+ T lymphocytes populations. Probably, the moment blood was drawn after completion of therapy could have influenced our results as we know that immunological reconstitution in patients with cHL may take several months. Further studies investigating these CD4+ T lymphocytes subpopulations together with functional assays will contribute not only to our understanding on the pathogenesis of cHL but also to the development of therapeutic strategies designed to manipulate regulatory activity. Given that the incidence of EBV-related cHL, disease presentation and severity are different in developing countries than in developed ones, we emphasize the importance of this ongoing Brazilian multicentric project. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4240-4240
    Abstract: CD4+CTLA-4+ T lymphocytes has long been recognized as regulatory T cells, potentially decreasing antitumor immune response. Augmentation of the immune response via blockade of CTLA-4 has shown an improvement in survival for patients with metastatic melanoma, which prompted the Food and Drug Administration (FDA) approval of the CTLA-4 function blocking antibody Ipilimumab for this disease. CD4+CD127+ T lymphocytes also participate in immune homeostasis and T-cell development. The increased expression of this marker on CD4+ T cells is associated with a effector phenotype. CD127-mediated signaling in human leukemia T-cells that may be of therapeutic value, namely regarding the potential use of PI3K and mTOR pharmacological inhibitors. Increased frequencies of regulatory CD4+ cells, together with decreased effector CD4+ cells in the tumor microenvironment and peripheral blood have been proposed as one of the mechanisms for the immunosuppression state observed in classical Hodgkin lymphoma (cHL) patients. However, little is known about CD4+ T cells subsets in patients with classical Hodgkin lymphoma (cHL) and how treatment can modify these cells. Objective The aim of the study was to evaluate the surface expression of CTLA-4 and CD127 on CD4+ T cells in peripheral blood mononuclear cells (PBMC) of patients with classical Hodgkin lymphoma (cHL) at diagnosis and post-treatment and correlate these findings with clinical and epidemiological aspects. Material and Methods This is an open multicentric study and, so far, we included 54 patients from december 2009 to July 2013. Thirty-four patients have completed therapy until July 2012 and were included in this study. Blood was drawn at diagnosis and post-treatment (1 to 4 months after completion of therapy). The T cell phenotype was evaluated by flow cytometry using CD3, CD4, CD8, CTLA-4 and CD127 and correlated to phenotypic and clinical parameters in uni- and multivariate models pre and post-treatment. Nineteen healthy blood donors volunteers were recruited as controls. In this study, only cHL patients whose histology could be confirmed and Epstein-Barr (EBV) association established were studied. All patients were HIV negative and received ABVD chemotherapy protocol and radiotherapy if necessary. Results From the 34 cHL patients recruited for this study, 17 (50%) were male, 16 (47%) had Epstein-Barr virus (EBV) related cHL, 27 (79%) patients presented with B symptoms and 18 (53%) patients had advanced diseases at diagnosis. The percentage of CD4+ T cells with CTLA-4 surface expression was significantly increased in patients with cHL at diagnosis compared with healthy controls (median 8.7 (0.8 - 30.3) vs 2.5 (0.7 - 11.2); P 〈 0.001). Additionally, CD4+CTLA-4+ T lymphocytes significantly decreased following treatment (8.7 (0.8 - 30.3) vs 3.9 (0.8 - 10.3); p=0.01), with values similar to healthy controls (3.9 vs 2.5; p=0.42). By contrast, CD4+CD127+ T lymphocytes were decreased at diagnosis, with values increasing after therapy (41.2 (3.3 – 75.7) vs 54.9 (17.1 – 81.3); p=0.002), similar to healthy controls (54.9 (17.1 – 81.3) vs 58.2 (41.2 – 89.8); p=0.21). The expression of CD127 on CD4+ T cells negative correlated with the expression of CTLA-4 (p 〈 0.001). In this study, these CD4+ T cells subpopulations were neither associated with treatment response nor relapse. The frequencies of these cells were not correlated with age, gender, disease stage, erythrocyte sedimentation rate (ESR), albumin levels and EBV status. Conclusions In this study we showed a negative correlation between CTLA-4 expression on CD4+ T cells with the expression of CD127 at diagnosis of patients with cHL. These results suggest a role of CTLA-4 and CD127 on Hodgkin lymphomagenesis, possibly negatively regulating host anti-tumor immune response. Further studies investigating these CD4+ T lymphocytes subpopulations with functional assays are warranted. The promising immunotherapy regimen targeting CTLA-4 and the use of drugs that alter CD127 signaling might be beneficial in classical Hodgkin lymphoma. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4778-4778
    Abstract: Abstract 4778 Cytotoxic T lymphocyte antigen-4 (CTLA-4) is one of the basic antigens involved in immune responses regulation associated with autoimmune diseases and cancer. Its key role in regulating the immune system has made CTLA-4 an attractive target for cancer. Augmentation of the immune response via blockade of CTLA-4 has shown an improvement in survival for patients with metastatic melanoma, which prompted the Food and Drug Administration (FDA) approval of the CTLA-4 function blocking antibody Ipilimumab for this disease. Objective: The aim of the study was to evaluate the surface expression of CTLA-4 on CD4+ T cells in peripheral blood mononuclear cells (PBMC) of patients with classical Hodgkin lymphoma (cHL) at diagnosis and post-treatment and correlate these findings with clinical and epidemiological aspects. Material and Methods: This is an open study and, so far, we included 35 patients from December 2009 to December 2011. Blood was drawn at diagnosis and post-treatment (1 to 4 months after completion of therapy). The T cell phenotype was evaluated by flow cytometry using CD3, CD4, CD8, CTLA-4 and correlated to phenotypic and clinical parameters in uni- and multivariate models pre and post-treatment. Eighteen healthy blood donors volunteers were recruited as controls. In this study, only cHL patients whose histology could be confirmed and Epstein-Barr (EBV) association established were studied. All patients were HIV negative and received ABVD chemotherapy protocol and radiotherapy if necessary. Three patients relapsed, and blood was also drawn at this time. Results: From the 35 cHL patients, 17 were EBV related and 18 EBV non-related. The percentage of CD4+ T cells with CTLA-4 surface expression was significantly increased in patients with cHL at diagnosis compared with healthy controls (median 7.36 vs 2.73; P 〈 0.001). Additionally, CD4+CTLA-4+ T lymphocytes significantly decreased following treatment and complete response (7.36 vs 4.53; p=0.008), with values similar to healthy controls (4.53 vs 2.73; p=0.07). Interestingly, CD4+CTLA-4+ T lymphocytes on relapse were significantly different from post-treatment values and similar to pre treatment. There was no difference on CD4+CTLA-4+ T lymphocytes in the EBV related and non-related cHL patients. Regarding patient's baseline characteristics, CD4+CTLA-4+ T lymphocytes strongly correlated with erythrocyte sedimentation rate (ESR) values (r=0.67; p=0.002). Conclusions: We showed that CD4+CTLA-4+ T lymphocytes are increased in Brazilian cHL patients at diagnosis compared with post-treatment values and healthy controls. These results suggest a role of CTLA-4 on Hodgkin lymphomagenesis, possibly negatively regulating host anti-tumor immune response. The promising immunotherapy regimen targeting CTLA-4 might be beneficial in classical Hodgkin lymphoma. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3913-3913
    Abstract: Introduction: Post-transplant lymphoproliferative disorders are a rare heterogenous group of diseases occurring in the setting of post-transplant immunossupression (IS). Clinically, extranodal involvement is common, and it occurs in the central nervous system (CNS) in approximately 7-15% of cases. Most data on PTLD-CNS are based on case series/reports and due to paucity of data no treatment algorithms have been established. In our series, we retrospectively analyzed 23 consecutively cases of PTLD-CNS in Hospital do Rim, Sao Paulo, Brazil. Methods: We retrospectively reviewed all cases of PTLD-CNS diagnosed between 2001 and 2014 at Hospital do Rim (HRim), a school hospital from the Federal University of São Paulo, Brazil. HRim is considered the leading renal transplant hospital in the world for the past 15 years. For this study, only PTLD patients with tumors whose histology could be confirmed by hemopathologist review, EBV-association established and whose clinical, epidemiological and laboratorial parameters could be retrieved were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of second-line therapy) or relapse. Results: From 2001 to 2014, from a total of 98 PTLD patients, 23 patients (23%) were diagnosed with PTLD-CNS. Median age at time of diagnosis was 36, with a male:female ratio of 0.9:1. Fifteen (65%) patients received anti-thymocyte globulin (ATG) at the time of transplant and 17 (74%) had at least one episode of acute rejection. The most common immunossupressive regimen (IR) consisted of cyclosporine or tacrolimus associated with prednisone and azathioprine (15, 65%). Median time from transplant to PTLD diagnosis was 31 months (ranging from 8.4 to 153). EBV was positive in tumor lymphocytes by in situ hybridization in 21 cases (91%). Monomorphic cases were diagnosed in 21 (91%) patients. All patients had their IR reduced, usually with suspension of azathioprine and calcineurin inhibitors and change from prednisone to dexamethasone, 19 (82%) patients underwent WBRt (from 25 to 40 Gy) together with intra-thecal (IT) chemotherapy with methotrexate (MTX) 12mg and dexamethasone 2mg. Only 1 patient received high dose MTX and died due to treatment-related toxicities 1 month after diagnosis and 2 patients died before starting WBRt due to disease progression and poor performance status (PS). For those patients who received WBRt together with IT chemotherapy, fourteen patients (74%) had CR, 2 patients (10%) had refractory disease and 3 patients (16%) had relapsed disease within 2 years. Overall Survival (OS) for the group treated with WBRt and IT chemotherapy was 62% in 5 years (CI95% 69-82%). In our series, induction therapy with ATG and acute rejection were associated with increased risk of PTLD-CNS. Age and PS at diagnosis were the only 2 factors predictive of survival. No serious cognitive impairment was identified among the survivors. Conclusions: The current study demonstrated that PTLD-CNS is a serious late EBV-induced B-cell lymphoma, mostly monomorphic with an incidence of 23%, higher than previously described in the post renal transplant setting. Treatment with immunossupression reduction, intrathecal chemotherapy and whole-brain radiotherapy showed a high CR rate with favorable survival in many cases. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
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  • 8
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5049-5049
    Abstract: In 1998, Hasenclever et al published the International Prognostic Factor for patients with advanced stage classical Hodgkin lymphoma (cHL). Since then, the IPS has been considered the most important prognostic score for cHL and has been validated in different populations, and also in early stage cHL. From the seven factors analyzed in the IPS, albumin is the only that can be influenced by environmental, economic and nutritional status. We hypothesized if, in developing countries, albumin should still be a prognostic factor, and if so, what is the ideal cutoff value. Objectives To assess if albumin at diagnosis of cHL patients in Brazil was prognostic for overall survival (OS) and progression free survival (PFS) and what would be the best cutoff. Patient and Methods This is a retrospective multicenter study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of cHL, diagnosed between April 1996 To January 2013, with clinical, epidemiological and laboratorial parameters available after a thorough chart review were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Advanced stage disease was defined as stage I or II with B symptoms and/or bulky disease and stage III or IV. Patients with conflicted data or loss of follow up were excluded from the analysis. Results A total of 179 patients were selected for this study. Nodular sclerosis subtype was diagnosed in 125 (68.9%) of all patients. Median age at diagnosis was 28 years old (ranging from 13-76). Only 22.9% of patients presented with early stage disease. ABVD chemotherapy protocol was the initial therapy in 91% of patients. Consolidation radiotherapy was done in 48.6%. Median serum albumin was 3.74 (range: 1.34 – 5.52). Median albumin for patients treated in private hospital was 3.6 (range: 2.7 – 4.7) in contrast to patients treated in public hospitals with a median level of 3.0 (range: 1.34 – 5.52), although this difference was not statistically different. Overall responses were: CR in 90%, Partial response/Refractory disease in 10%; one patient died due to treatment-related toxicity. Overall Survival (OS) for the entire group was 93% in 5 years (CI95% 87-96%), with a progression free survival (PFS) of 79% (CI95% 73-86%). When applying the cutoff of 4g/dL, albumin was not related to OS (91% vs 98%, p=ns) or PFS (85 vs 77%, p=ns). However, an albumin value greater than 2g/dL was related to a better OS (94% vs 71%, p=0.01). Conclusions Prognostic factors may differ from different studied populations. This is particularly truth for albumin, which is the only IPS factor influenced by the environment. In our study, however, albumin was not significantly related to OS or PFS, unless when a cutoff of 2g/dL was used. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5054-5054
    Abstract: Introduction: Post-Transplant Lymphoproliferative Disease (PTLD) is a rarewell-recognized group of lymphoid and or plasmacytic proliferations that occur following both solid organ (SOT) and allogenic hematopoietic stem cell transplantation (HSCT) as a result of immunossupression. A continuum of disease has been described, including early lesions, polymorphic PTLD and monomorphic PTLD. Epstein-bar virus (EBV) is considered the most important causative factor, with EBV positivity observed within up 90% of tumor lymphocytes. Optimal risk stratifications specific to kidney transplantation are still lacking. Patient and Methods: In our series, we retrospectively analyzed 98 consecutively cases of PTLD diagnosed between 2001 and 2014 at Hospital do Rim (HRim), a school hospital from the Federal University of São Paulo, São Paulo, Brazil. HRim is considered the leading renal transplant hospital in the world for the past 15 years. For this study, only PTLD patients with tumors whose histology could be confirmed by hemopathologist review, EBV-association established and whose clinical, epidemiological and laboratorial parameters could be retrieved were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of second-line therapy) or relapse. Patients with conflicted data or loss of follow up were excluded. Results: A total of 98 patients were diagnosed with PTLD from 7665 renal transplants performed in this period, with a incidence of 1,3%. Two patients were excluded from the analysis due to conflicting clinical data. Median age at diagnosis was 41.4 years (range from 4-74), with a 0,6:1 Female:Male ratio. Median time of transplant to PTLD diagnosis was 56 months (range 1-967). Thirty-six patients (37.5%) received anti-thymocyte globulin (ATG), and the most common immunossupressive regimen (IR) consisted of cyclosporine or tacrolimus associated with prednisone and azathioprine (66, 69%). Monomorphic PTLD was observed in 75 (78%) patients, and two patients presented with HL. EBV positivity was seen in 67 patients (70.5%), being more frequent within PTLD cases diagnosed during the first 3 years of transplantation (90%). All patients had their IR reduced after PTLD diagnosis. The incidence of loss of engraftment following IR reduction was 19% (20 patients). Overall responses were: CR in 67% (n=64) and Partial response/Refractory disease in 33% (n=32); 30 patients died due to treatment-related toxicity and/or disease progression. Overall Survival (OS) for the entire group was 63% in 5 years (CI95% 73-83%), with a progression free survival (PFS) of 58% (CI95% 91-97%). EBV positivity was seen in 67 patients (70.5%). Median number of extra nodal sites involved was 1,2. The median overall survival time was 97 months. Patient survival following diagnosis was 77% at 1 year, 63% at 5 years and 38% at 10 years. The most common extra-nodal sites involved were: Gastro-intestinal Tract (43, 45%) followed by Central Nervous System (23, 24%). Extra nodal involvement was correlated with poorer outcome (p 0.014) as was the loss of engraftment (p 〈 0.0001). Conclusions: PTLD is a rare complication of immunossupression, usually related to EBV, specially for PTLD diagnosed within the first 3 years of transplantation. Basically, the initial treatment consists of reduction or withdrawal of the immunossupressive regimen followed by specific imuno-chemotherapy as needed. In our cohort, the incidence of loss of engraftment was low, although it was correlated with inferior outcome, together with extranodal involvement. To date this is the largest cohort of post-renal transplant lymphoproliferative disease ever reported. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5044-5044
    Abstract: Introduction: Post-Transplant Lymphoproliferative Disease (PTLD) is a well-recognized group of lymphoid and or plasmacytic proliferations that occur following both solid organ (SOT) and allogenic hematopoietic stem cell transplantation (HSCT) as a result of immunossupression. A continuum of disease has been described, including early lesions, polymorphic PTLD and monomorphic PTLD. Epstein-bar virus (EBV) is considered the most important causative factor, with EBV positivity observed within up 90% of tumor lymphocytes. There is paucity of prognostic factors in PTLD, but studies have shown that IPI, Performance status and number of disease sites are related to mortality. LMR has shown to be prognostic in different lymphomas, including Hodgkin's Lymphoma (HL), Diffuse Large B-cell lymphomas among others. Objectives: To assess the role of lymphocyte/monocyte ratio at diagnosis in predicting outcome and survival in PTLD patients. Patient and Methods: This is a retrospective study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of PTLD, diagnosed from 2001 to 2015, with clinical, epidemiological and laboratorial parameters available were included in this study. Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Patients with conflicted data or loss of follow up were excluded from the analysis. Results: A total of 98 patients were diagnosed with PTLD in the study period. Two patients were excluded from the analysis due to conflict clinical data. Median age at diagnosis was 41.4 years (range from 4-74), with a 0,6:1 Female:Male ratio. Median time of transplant to PTLD was 56 months (range 0-967). Twenty-six patients (27%) received anti-thymocyte globulin (ATG), and the most common immunossupressive regimens consisted of cyclosporine or tacrolimus associated with prednisone and azathioprine (68,7%). Monomorphic PTLD was observed in 78% of patients, and two patients presented with HL. With a median follow up of 33.3 months, 35% of patients died. In a univariate analysis, the number of extranodal sites and LMR were associated with worst survival (p=0.026 and p=0.004). Conclusions: PTLD is a known complication of immunossupresion, usually related to EBV. In our cohort of 96 kidney recipients with PTLD, LMR and number of extranodal sites was associated with inferior outcome. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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