Browsing by Autor "Sally Paredes"

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Biological and Classical Prognostic Factors with Impact on Overall Survival in Patients with Early Stage (I/II) Diffuse Large B-Cell Lymphoma: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)
(Elsevier BV, 2021) Luís Villela; Brady Beltrán; Denisse Castro; Ana Florencia Ramírez‐Ibarguen; Marialejandra Alejandra Torres Viera; Guilherme Fleury Perini; Carmen Lome; Myrna Candelaria; Henry Idrobo; Sally Paredes
Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype. Early stage (I/II) disease is seen in up to 30% of all DLBCL cases, and although outcomes in this subgroup have been reported as optimal, relapses can still occur. Prognostic models such as the International Prognostic Index (Miller, NEJM, 1998) continues to be utilized for risk stratification in DLBCL. However, despite its limitations and lack of validation in specific demographic groups such as Latin American patients, no prognostic models exist for the evaluation of limited stage DLBCL. Therefore, we aim to investigate different clinico-epidemiological and laboratory variables and its impact on survival in early stage DLBCL. Methods: We conducted a retrospective study of newly diagnosed patients with early stage DLBCL. Using the Grupo de Estudio Latinoamericano de Linfroproliferativos (GELL) database, we selected patients that had early stage disease, defined as non-bulky stage I or II. The variables analyzed included demographic and clinical variables (e.g., age, ECOG performance status), the International Prognostic Index (IPI), and laboratory variables such as serum albumin, serum lactate dehydrogenase (LDH), serum beta-2-microglobulin, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (LNR), and the platelet-lymphocyte ratio (PLR). To determine the variables associated with mortality, univariate and multivariate Cox regression (step-wise type) analysis was performed. Kaplan-Meier and log-rank test were used for survival analysis. Outcomes with a p-value &lt;0.05 were considered statistically significant. Results: We identified 1,375 patients with DLBCL; 503 were identified as early stage DLBCL of whom 498 had sufficient data for analysis. Almost all cases (n=483, 96%) had nodal disease as the primary site, and 15 (4%) extranodal, all within the gastrointestinal tract. There was a slight female predominance (51.8%). The median age at diagnosis was 64 (IQR: 50 -73) with 57.4% older than &gt;65 years. ECOG performance status of &lt;2 was seen in 77.2% of cases; elevated serum LDH in 32.4%; and elevated serum beta-2-microglobulin in 5.6% (n=11/192). Based on previous data, we evaluated and calculated variables that have been suggested as independent negative prognostic factors for overall survival; the proportion of patients with serum albumin &lt;3.5 mg/dL; LMR &lt;2, NLR &gt;4, and PLR &gt;376 was 34.4%, 10.3%, 9.2%, and 4.7% respectively. With a median follow-up of 45 months, the median 5-year overall survival (OS) rate was 72%. The therapy approaches used, response rates and outcomes with these approaches will be presented at the meeting. Results of the univariate and multivariate analysis are summarized in Table 1. We found that age over 65, ECOG performance status, serum albumin level, beta-2-microglobulin level, LDH ratio, LMR, NLR, PLR, and BCL-2 positivity by immunohistochemistry (IHC) were prognostic factors for OS in the univariate analysis. However, in the multivariate analysis, only NLR, serum albumin level and ECOG performance status were independent factor for worse prognosis. Survival rates were significantly shorter in patients with serum albumin &lt;3.5 g/dL (5-year OS of 49% versus 79%, respectively; p&lt;0.0001); NLR &gt;4 (5-year OS of 46% versus 73%, respectively: p=0.0013); and ECOG performance status ≥2 (5-year OS of 51% versus 74%, respectively; p&lt;0.0001) (Figures 1 to 3). Conclusion: In this large cohort of Latin American patients with early stage DLBCL most patients were older than 65, had nodal disease as the primary site, good performance status, with only a third of patients exhibiting elevated LDH. Moreover, we found serum albumin &lt;3.5 g/dL, NLR &gt;4 and ECOG ≥2 as negative prognostic factors for poor survival in early stage DLBCL. We are currently validating our findings in a prospective cohort of Latin American DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality. Figure 1 Figure 1. Disclosures Otero: Astra Zeneca: Current Employment. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.
Extranodal NK/T-Cell Lymphoma in Latin America: A Retrospective Multinational Analysis of Clinical Features, Therapeutic Approaches and Outcomes from the Latin American Group of Lymphoproliferative Disorders (GELL)
(Elsevier BV, 2024) Fabiola Valvert; Omar Eduardo Fernandez Vargas; Sally Paredes; Luís Alberto de Pádua Covas Lage; Luis Mario Villela Martínez; Jose Marcial Macias Abasto; Victoria Irigoín; Cesar Camilo Carias Alvado; Juan Barrios; Brenda L. Acosta‐Maldonado
Background Extranodal NK/T-cell lymphoma (ENKTL) is a rare subtype of Epstein-Barr virus (EBV)-related non-Hodgkin lymphoma. It has a distinct geographic and ethnic predilection, being more common in East Asia and Latin America (LATAM). ENKTL is known for its poor prognosis, largely due to its aggressive nature and the frequent development of resistance to conventional chemotherapies. However, the introduction of asparaginase-based regimens combined with radiotherapy has led to improved outcomes in recent years. Despite these advances, there is no established standard of care, especially in resource-limited settings like LATAM. This study aims to fill the knowledge gap regarding ENKTL in LATAM, by analyzing the clinical features, therapeutic approaches, and outcomes of patients (pts) with ENKTL in this region. Methods A retrospective, multicenter study was conducted including pts aged ≥18 with newly diagnosed ENKTL from Guatemala (n=92), Mexico (n=87), Brazil (n=92), Peru (n=19), Bolivia (n=12) and Uruguay (n=1) from 2000 to 2023. Baseline demographics, clinical-biological disease characteristics, treatment patterns, and outcomes were collected and analyzed. Primary endpoint was overall survival (OS) defined as time from diagnosis to death from any cause. Kaplan-Meier method and Log-rank tests were used to estimate and compare survival probabilities. Results A total of 303 pts were included, with a median age at diagnosis of 44 years (18-86) and a male predominance (59.41%). Localized disease (stage I/II) was seen in 59% (n=180) and advanced (stage III/IV) in 41% of pts by TNM. Clinically, pts are commonly presented with visible ulcerative lesions (53.5%) or palate perforation (31.3%). B symptoms were seen in 57.8%, high LDH in 42.9%, bulky disease (&gt;7 cm) in 16.7% and hemophagocytic lymphohistiocytosis in 15.8%. Most pts (88.4%, n=268) received first line therapy, including concurrent or sequential radiotherapy plus chemotherapy (68%), radiotherapy alone (6%) and chemotherapy alone (26%). Among those managed with systemic chemotherapy (with or without radiation therapy), 28% (n=71/251) were treated with anthracycline- (i.e. CHOP); 13% (n=33/251) with platinum; 36% (n=90/251) with asparaginase; and 23% (n=57/251) with other regimens. Complete response rates were seen in 38.6% of pts treated anthracycline- (47.7% localized vs 22.2% advanced); 66.7% with platinum-; (66.7% localized vs 64.3% advanced) and 48.9% with asparaginase-based regimens (63.3% localized vs 34.1% advanced). Responses were significantly better for platinum- (p=0.019) and worse for anthracycline-based therapy (p=0.02) in pts with advanced stage. No differences in responses by therapy regimens were seen in pts with localized disease. Median follow up was reached at 12 months and 1-year OS of 59.4%. Worse OS was seen in pts with advanced vs early stage 6 months vs 28 months respectively; (p=0,001, HR 2,73, 95% CI 1.9-3.9), indistinctive of the type of treatment. Pts with early stage disease had a median OS of 38.6, 36.6 and 26.7 months for asparaginase-, anthracycline- and platinum-based treatments, respectively. Less favorable results were seen for advanced stages with median OS of 13.8, 9.8 and 17.6 months, respectively. The leading causes of death were progression (17%, n=52), infection (10%, n=29) and lack of access for treatment (7%, n=22). Conclusion This multicenter study represents one of the largest analyses of ENKTL in LATAM, providing valuable insights into the clinical, treatment patterns and outcome of this aggressive malignancy. Our findings highlight the poor prognosis associated with advanced-stage disease, irrespective of treatment regimen, underscoring the need for early detection and timely intervention. While asparaginase-based therapies showed promise in localized disease, outcomes for advanced stages remain suboptimal, emphasizing the limitations of current treatment strategies in resource-limited settings. The study also reveals significant barriers to care, including limited access to effective therapy, which contributes to the high mortality rate from disease progression and infections. These results underscore the urgent need for improved healthcare infrastructure and tailored therapeutic approaches to enhance outcomes for ENKTL pts in LATAM.
Real-world treatment and outcomes of Mantle Cell Lymphoma in Latin America: A multinational cohort analysis
(Elsevier BV, 2025) Adriana Bornacelly; Marialejandra Torres Viera; Luis Mario Villela Martínez; Luis Felipe Rubalcava; Carolina Oliver; Brady Beltrán; Denisse Castro; Sally Paredes; José Luis Álvarez Macías; Bruno Samaniego
Abstract Background: Mantle cell lymphoma (MCL) is a rare, aggressive B-cell malignancy with heterogeneous clinical behavior and poor long-term outcomes. While treatment advances have significantly improved outcomes in high-income countries, little is known about how the real-world treatments and survival in LATAM. This study aims to characterize the clinical presentation, therapeutic approaches, transplantation and novel agents access, and survival outcomes in LATAM patients with MCL, and to identify country- and system-level factors contributing to variability in care. Methods This was a retrospective, multicenter cohort study conducted across 19 institutions in 8 LATAM countries between 2015 and 2024. Adult patients (≥18y) diagnosed with MCL were included when complete clinical, treatment, and outcome data were available. Variables analyzed included demographics, stage, prognostic indexes, frontline and salvage therapies, autologous stem cell transplantation (ASCT), access to targeted agents, and survival. Subgroup analyses were conducted by age (&lt;65 vs. ≥65), country, and institution type (public vs. academic/private). Primary endpoints were overall survival (OS), progression-free survival (PFS), and treatment response. Secondary endpoints included ASCT eligibility and use, access to maintenance therapy, and uptake of second-line (2L) targeted therapies. Results A total of 222 patients met the inclusion criteria. Median age was 64 years (range, 34–89), males predominance (70.4%). At diagnosis, 72.5% of patients had stage III/IV, 66% extra nodal involvement, 62.4% bone marrow infiltration, 49.8% elevated LDH, and 54.6% showed elevated β2-microglobulin. ECOG ps ≥2 was observed in 57.9% of patients. High-risk MIPI was present 47.8% overall and significantly more common in older patients (≥65y: 69.2% vs 41.8%; p=0.001). 1L therapy varied: 43.6% received cytarabine-based regimens, 25.3% Rituximab (R)-CHOP, and 20% R-Bendamustine (RB). Patients &lt;65y received more intensive therapy (69.2%), while those ≥65y received RB more often (37%). Public hospitals favored R-CHOP (41.2%), whereas academic/private centers preferred cytarabine-based regimens (50%). Watch&Wait was used in 9.9%. Among transplant-eligible patients, only 43.4% (n=51) underwent ASCT; main barrier was medical criteria (e.g., comorbidities, poor performance status, suboptimal response to 1L) (75%) rather than financial. R-maintenance (RM) therapy increased after 2018 from 53.3% to 63.4%. Only 19.4% of patients &lt;65y and 27.4% of those ≥65y received RM after 1L induction chemoimmunotherapy. Among transplanted patients, the post-ASCT RM group showed lower 3-year mortality (22.6% vs 33.3%) and improved overall survival. 2L therapy was given to 34% of patients. BTKi were used 32.1%, venetoclax 3.6%, and almost exclusively in private settings. BTKi access was markedly lower in public institutions (11.9% vs. 52.4%). Countries such as Cuba, Peru, and Bolivia reported no access to targeted therapies. Most relapsed/refractory patients received chemo-based regimens, resulting in modest outcomes. Complete response (CR), partial response (PR), and progression to 2L therapy were 31.4%, 41.4%, and 27.1%, respectively. Survival analysis included 218 patients with 81 deaths. Median follow-up was 26.8 months (range: IQR 12.0-44.9). OS at 12, 24, and 36 months was 88%, 77.4%, and 68.4%, respectively. Median OS was 80.5 months (95% CI: 60.1–106.3). PFS at 12, 24, and 36 months was 72.9%, 55.1%, and 47.9%; median PFS was 29.7 months. ASCT significantly improved survival, 3-year OS 79.9% vs. 61.3%; median OS 9.9 vs. 4.5y; HR 2.7, 95% CI: 1.43–5.13, p=0.002). Conclusions This real-world LATAM cohort reveals high-risk clinical profiles at diagnosis and disparities in access to transplant, maintenance, and novel agents. While ASCT showed a clear survival benefit, its implementation remains uneven. RM, post-ASCT and in older patients, was underused despite evidence of benefit and absence of financial barriers. Access to 2L targeted therapies remains extremely limited in public institutions and absent in several countries, impacting post-relapse outcomes. Despite these gaps, survival metrics appear comparable to international cohorts, suggesting biological or demographic resilience. These findings underscore the need for equitable access, regional treatment harmonization, and expansion of clinical trial infrastructure across LATAM.
Serum Albumin and Neutrophil-to-Lymphocyte Ratio, Two Independent Factor Predicting Survival in Patients with Follicular Lymphoma: A Multi-Institutional Retrospective Cohort of 741 FL, from the Latin American Lymphoproliferative Study Group (GELL)
(Elsevier BV, 2021) Marialejandra Alejandra Torres Viera; Luís Villela; Brady Beltrán; Denisse Castro; Myrna Candelaria; Henry Idrobo; Victoria Otero; Alana Von Glasenapp; Fabiola Valvert; Sally Paredes
Abstract Introduction: The neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in different cancers. Although the exact mechanism remains to be elucidated, reduced lymphocyte intra tumor infiltration coupled with the formation of neutrophil extracellular traps (or NETosis) have been postulated as endogenous mechanisms for tissue damage and inflammation. Along this line, serum albumin has also been studied as a biomarker of inflammation and has been associated to prognosis in certain cancers. We have previously reported on the prognostic value of the NLR and serum albumin in diffuse large B-cell lymphoma (Villela, ASH meeting, 2019; Castro, ASH meeting, 2019) and peripheral T-cell lymphoma, not otherwise specified (Idrobo, ASH meeting, 2019), but nothing on follicular lymphoma (FL) yet. Therefore, we aim to investigate the role of different biomarkers on the prognosis of patients with FL diagnosed and managed in Latin America. Methods: We analyzed patients with FL diagnosed between 2010 and 2020 from 30 centers in 10 Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS) in relation to different biomarkers. Kaplan-Meier and log-rank test were used for survival analysis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios (HR) with a 95% confidence interval (CI) and adjusted to the Follicular Lymphoma International Prognostic Index (FLIPI) score. Outcomes with a p-value &lt;0.05 were considered statistically significant. Results: We identified 939 FL patients; 741 were included for the final analysis (median age 58 y, female 52%). There was no significant correlation between the NLR and other clinical factors such as: age, clinical stage, histological FL grading, and chemotherapy regimen used. A cutoff of 2.15 for NLR was defined as the maximum point for sensitivity and specificity based on ROC analysis. Table 1 and 2 summarizes the results from the univariate and multivariate analysis for 2 years OS and PFS, respectively. Both, serum albumin &lt;3.5 g/dL and a NLR &gt;2.15 were independently associated with worse OS (adjusted, aHR 2.48 [1.26-4.91], p=0.009; and 2.55 [1.21-5.37], p=0.014) and PFS (aHR 1.62 [1.03-2.55], p=0.038; 2.22 [1.45-3.40], p&lt;0.001), respectively. The lymphocyte:monocyte ratio (LMR) was not found to be prognostic for OS or PFS, although with a trend for worse PFS with a LMR ≤2.5. With a median follow of 43 months, (95% CI: 40-47), the survival rates in patients with FL and albumin &lt;3.5 were OS of 83% (vs. 95%) and PFS of 70% (vs. 83%); whereas in patients with NLR &gt;2.15 the survival rates were OS of 91% (vs. 96%) and PFS of 75% (vs. 88%) (Figures 1 and 2; table 3). Conclusions: In this study, serum albumin and NLR emerge as reliable predictors for survival for FL patients in Latin America. Although these markers have been associated to an increased inflammatory state in cancer patients; other factors such as poor nutritional status, and advanced disease stage due to delayed access to specialized cancer care in our region may have contributed to the observed outcome. Further studies are needed to better understand the role of these biomarkers on lymphoma care and to validate our findings. Lastly, we are currently working on evaluating these biomarkers on existing prognostic models and to improve prognostication for FL patients in Latin America. Figure 1 Figure 1. Disclosures Otero: ASTRA ZENECA: Current Employment. Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Roche: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau; Takeda: Speakers Bureau; Abbvie: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.