Browsing by Autor "Denisse Castro"

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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.
Genetics of Multiple Myeloma in Latin America
(Elsevier BV, 2022) Paola Leone; Virginia Abello; Cristian Gerardo Alvarado; J. D. Ruiz Alvarez; Gabriel Borelli; Maria Elena Del Rocio Buenaño; Wendy Cabrera; Fernando Camacho; Milton Rafael Carranza Orellana; Denisse Castro
Multiple Myeloma (MM) is a plasma cell tumor, occurs more commonly in men than in women, differences in incidence by ethnic group have been reported, and exposure to different genotoxic agents has been described as risk factors. Epidemiological and genetic studies of MM in Latin America are scarce, so we created the Ibero-American Network for Multiple Myeloma Research (REDIMM), for the exchange and dissemination of information, standardization of protocols and genetic technologies. Eighteen countries were invited and after 5 years of work, REDIMM has 11 participating countries. Each country, with the exception of the United States whose representative explains the palliative care model, presents demographic, clinical laboratory, genetic, and type of treatment information. Each country manages the MM according to the conditions of the environment and the health system; however, the communication between the countries of the network allows the transfer of knowledge that is beneficial in the diagnosis and follow-up. The countries that make up the REDIMM would like to have more technology to make an early and accurate diagnosis of MM. However, the scenario of many Latin American countries is the lack of clinical laboratory tests and in some the total absence of genetics laboratories. In addition, the difficulties for diagnosis are added that it is usually late since patients move to large cities in advanced stages. The research shows that MM has a lower incidence than reported in North America and Europe, a low incidence of monoclonal gammopathy of uncertain significance in the region is described, younger patients than described in other populations are observed, and a relationship between exposure to genotoxics and the development of this cancer is evident. Non-hyperdiploid cases with a worse prognosis predominate, access to treatment is limited and survival time is shorter than reported in the United States and Europe. In Ecuadorian mestizo populations, differences in age and gender ratio are observed according to the predominant ancestry component studied by AIMs-INDELs. We conclude that characterizing the situation of the MM in Latin America will have an immediate and medium-term benefit for all participating institutions, and we hope in Latin America, which will have a favorable impact on myeloma patients.
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.
Updated Analysis Confirms Sustained Poor Prognosis of COVID-19 in Patients with Lymphoma in Latin America: A Cohort of 160 Patients from Gell
(Elsevier BV, 2021) Guilherme Fleury Perini; Luís Villela; Brady Beltrán; Denisse Castro; Victoria Otero; Mariana Kalmus; Lorena Fiad; Camila Peña; Henry Idrobo; Myrna Candelaria
Abstract Updated analysis confirms sustained poor prognosis of COVID-19 in patients with lymphoma in Latin America: A cohort of 160 patients from GELL. Introduction: Ongoing SARS-COV-2 pandemic has impacted the management of cancer patients worldwide. Several reports have demonstrated inferior outcomes of patients with hematological malignancies, including higher rates of intensive care unit admission, need for mechanical ventilation and death. The impact of COVID-19 is profound in resource-restricted countries, including Latin America. Most cohorts reported have not included patients from Latin America, and there is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. Grupo de Estudio De Linfoproliferativos En Latino-America (GELL )is a collaborative network of hematological centers in 13 countries in Latin America. We report updated outcomes of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: We conducted a retrospective study including patients with a diagnosis of lymphoma and COVID-19 infection. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were excluded from the analysis We defined active disease as follow: (1) patients with detectable disease either prior to initiating therapy or upon relapse, and/or (2) patients undergoing active cancer treatment. The primary outcome was overall survival at 100 days. Survival curves were estimated using the Kaplan Meier method. Uni and multivariable analysis were carried out with Cox model. Results: A total of 160 patients were available for analysis. Median age was 60 years old. Hypertension was the most common comorbidity (33%). Most patients had aggressive lymphomas (62%), including 43% of patients with diffuse large B-Cell lymphoma (DLBCL). Follicular lymphomas were observed in 13% of patients and Hodgkin lymphoma in 12.5% of patients. With a median follow-up of 37 days, the 100-day OS was 64% (95CI 56-74%, fig. 1). In univariate analysis, age (HR 1.03, p=0.0025), hypertension (HR 2.01, p=0.017), &gt;1 number of prior lines (HR 2.78, p=0.011), patients currently on treatment (HR 1.83, p=0.043), ferritin &gt;2000 ng/mL (HR 4.74 p=0.00047) were associated with inferior OS. In multivariate analysis, age (HR 1.03, p=0.0026) and patients currently on treatment (HR 1.82, p=0.04) had inferior OS. There was a trend towards inferior outcomes in patients receiving monoclonal antibodies in univariate analysis (HR 1.82, p=0.081) but not in multivariable analysis (HR=1.29, p=0.48). Use of steroids was not statistically related to mortality (HR 1.79, p=0.074). Finally, contrary to other cohorts, no improvement in OS was observed in patients diagnosed later on the pandemic (fig. 2). Conclusion: In this large cohort of Latin American patients with lymphoma malignancies, our updated analysis showed a maintained dismal prognosis with COVID-19 infection. With a median follow up of 37 days, the 100-day OS was 64%. Older age and ongoing active cancer treatment were significantly associated with mortality. The use of monoclonal antibodies and systemic corticosteroids were not statistically associated to poor survival. Current efforts are focused on improving immunization in the Latin American population. There is an unmet need for improving survival in patients with hematologic malignancies and COVID-19 infection. Figure 1 Figure 1. Disclosures Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Otero: ASTRA ZENECA: Current Employment. Abello: Dr Reddy's: Research Funding; Amgen: Honoraria; Janssen: Honoraria. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.