Publications by authors named "Elena Tuna-Aguilar"

11 Publications

  • Page 1 of 1

Causes of erythrocytosis and its impact as a risk factor for thrombosis according to etiology: experience in a referral center in Mexico City.

Blood Res 2021 Sep;56(3):166-174

Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Background: Thrombotic events are well documented in primary erythrocytosis, but it is uncertain if secondary etiologies increase the risk of thrombosis. This study aimed to determine the causes of erythrocytosis and to identify its impact as a risk factor for thrombosis.

Methods: Data were obtained from patients with erythrocytosis between 2000 and 2017 at a referral hospital in Mexico City. Erythrocytosis was defined according to the 2016 WHO classification. Time to thrombosis, major bleeding, or death were compared among groups of patients defined by the etiology of erythrocytosis using a Cox regression model, adjusting for cardiovascular risk factors.

Results: In total, 330 patients with erythrocytosis were studied. The main etiologies of erythrocytosis were obstructive sleep apnea (OSA) in 29%, polycythemia vera (PV) in 18%, and chronic lung disease (CLD) in 9.4% of the patients. The incidence rate of thrombosis was significantly higher in patients with PV and CLD than that in patients with OSA (incidence rates of 4.51 and 6.24 vs. 1.46 cases per 100 person-years, =0.009), as well as the mortality rate (mortality rates of 2.72 and 2.43 vs. 0.17 cases per 100 person-years, =0.003).

Conclusion: The risk of thrombosis in CLD with erythrocytosis was comparable to that in patients with PV. Further larger-scale studies are needed to confirm these findings and evaluate the benefits of preventive management of COPD with erythrocytosis similar to PV.
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http://dx.doi.org/10.5045/br.2021.2021111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478616PMC
September 2021

Real-world analysis of treatment patterns and clinical outcomes in patients with newly diagnosed chronic lymphocytic leukemia from seven Latin American countries.

Hematology 2020 Dec;25(1):366-371

Janssen Cilag Farmaceutica SA, Buenos Aires, Argentina.

Objective: To describe chronic lymphocytic leukemia (CLL) treatment patterns and patient outcomes in Latin America.

Methods: This chart review study (NCT02559583; 2008-2015)evaluated time to progression (TTP) and overall survival (OS) outcomes among patients with CLL who initiate done (= 261) to two ( = 96) lines of therapy (LOT) since diagnosis. Differences in TTP and OS were assessed by Kaplan-Meier analysis, with a log-rank test for statistical significance. Association between therapeutic regimen and risk for disease progression or death was estimated using Cox proportional hazard regression.

Results: The most commonly prescribed therapies in both LOTs were chlorambucil-, followed by fludarabine- and cyclophosphamide (C)/CHOP-based therapies. Chlorambucil- and C/CHOP-based therapies were largely prescribed to elderly patients (≥65 years) while fludarabine-based therapy was predominantly used by younger patients (≤65 years). In LOT1, relative to chlorambucil-administered patients, those prescribed fludarabine-based therapies had lower risk of disease progression (hazard ratio [HR] and 95% confidence interval [CI] 0.32 [0.19-0.54]), whereas C/CHOP-prescribed patients had higher risk (HR 95%CI 1.88 [1.17-3.04]). Similar results were observed in LOT2. There was no difference in OS between treatments in both LOTs.

Discussion: Novel therapies such as kinase inhibitors were rarely prescribed in LOT1 or LOT2in Latin America. The greater TTP observed forfludarabine-based therapies could be attributed to the fact that fludarabine-based therapies are predominantly administered to young and healthy patients.

Conclusion: Chlorambucil-based therapy, which has limited benefits, is frequently prescribed in Latin America. Prescribing novel agents for fludarabine-based therapy-ineligible patients with CLL is the need of the hour. ClinicalTrials.gov identifier: NCT02559583.
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http://dx.doi.org/10.1080/16078454.2020.1833504DOI Listing
December 2020

Epidemiology of Hematologic Malignancies in Real-World Settings: Findings From the Hemato-Oncology Latin America Observational Registry Study.

J Glob Oncol 2019 11;5:1-19

Instituto de Ensino e Pesquisas São Lucas, São Paulo, Brazil.

Purpose: Limited information is available on multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL) management in Latin America. The primary objective of the Hemato-Oncology Latin America (HOLA) study was to describe patient characteristics and treatment patterns of Latin American patients with MM, CLL, and NHL.

Methods: This study was a multicenter, retrospective, medical chart review of patients with MM, CLL, and NHL in Latin America identified between January 1, 2006, and December 31, 2015. Included were adults with at least 1 year of follow-up (except in cases of death within 1 year of diagnosis) treated at 30 oncology hospitals (Argentina, 5; Brazil, 9; Chile, 1; Colombia, 5; Mexico, 6; Panama/Guatemala, 4).

Results: Of 5,140 patients, 2,967 (57.7%) had NHL, 1,518 (29.5%) MM, and 655 (12.7%) CLL. Median follow-up was 2.2 years for MM, 3.0 years for CLL, and 2.2 years for NHL, and approximately 26% died during the study observation period. Most patients had at least one comorbidity at diagnosis. The most frequent induction regimen was thalidomide-based chemotherapy for MM and chlorambucil with or without prednisone for CLL. Most patients with NHL had diffuse large B-cell lymphoma (DLBCL; 49.1%) or follicular lymphoma (FL; 19.5%). The majority of patients with DLBCL or FL received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Conclusion: The HOLA study generated an unprecedented level of high-quality, real-world evidence on characteristics and treatment patterns of patients with hematologic malignancies. Regional disparities in patient characteristics may reflect differences in ethnoracial identity and level of access to care. These data provide needed real-world evidence to understand the disease landscape in Latin America and may be used to inform clinical and health policy decision making.
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http://dx.doi.org/10.1200/JGO.19.00025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882510PMC
November 2019

Impact of Additional Cytogenetic Abnormalities on the Clinical Behavior of Patients With Chronic Myeloid Leukemia: Report on a Latin American Population.

Clin Lymphoma Myeloma Leuk 2019 06 21;19(6):e299-e306. Epub 2019 Feb 21.

Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Introduction: Additional cytogenetic abnormalities (ACA) in patients with chronic myeloid leukemia (CML) are related to an increased risk of treatment failure, leukemic progression, and decreased survival. Currently, there are scarce data available for the Latin American population. The aim of this study was to outline the impact of ACA emergence in Mexican patients with CML.

Methods: We retrospectively analyzed clinical data from adult patients with CML treated with upfront imatinib between January 2001 and December 2016. Two groups were defined for comparison according to the presence or absence of ACA.

Results: Ninety-seven patients were included. ACAs were found in 30 patients, 20% at diagnosis and 80% during follow-up. In 90% of the patients, ACA emergence was detected in the CML-chronic phase. Regarding clinical outcomes, the complete cytogenetic response rate (16.5% vs. 59.8%; P < .001), progression-free survival (PFS) at 10 years (76% vs. 95%; P = .009), and failure-free survival (FFS) at 10 years (16% vs. 73%; P < .001) were significantly inferior in the ACA group. Multivariate analysis confirmed that ACA emergence was a deleterious independent prognostic factor for PFS (hazard ratio [HR] 8.9; 95% confidence interval [CI] 1.35-58.4; P = .023) and FFS (HR 3.7; 95% CI 1.54-8.58; P = .003).

Conclusions: This study confirms previously reported data regarding the adverse impact of ACA over clinical outcomes in a Latin American population.
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http://dx.doi.org/10.1016/j.clml.2019.02.007DOI Listing
June 2019

Prognostic Factors and Outcomes in Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-center Experience.

Clin Lymphoma Myeloma Leuk 2018 10 30;18(10):e373-e380. Epub 2018 Jun 30.

Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico. Electronic address:

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a disorder caused by severe immune activation. There are no specific criteria to establish the diagnosis in adults; however, the HLH-04 criteria are among the most commonly used. The HScore is a non-validated tool that can also be useful for HLH diagnosis.

Patients And Methods: We describe the prognostic factors and outcomes of 64 adults diagnosed with HLH in a reference medical center in Mexico City. We included patients ≥ 18 years with HLH, diagnosed and treated at our institution from 1998 to 2016.

Results: The median age was 35 years (range, 18-77 years). The underlying cause of HLH was lymphoma in 33 (51.56%) patients (MA-HLH). Cutaneous involvement was more frequent in MA-HLH (33.33%), when compared with patients with non-malignancy associated HLH (NM-HLH) (9.68%) (P = .022). Neurologic symptoms were more frequent in NM-HLH (25.81%) versus MA-HLH (6.06%) (P = .032). After a median follow-up of 14 months (range, 0-216 months), 30-day mortality was 26.56%. Three-year overall survival (OS) was higher for patients with MA-HLH compared with patients with NM-HLH (41% vs. 22.5%; P = .046). Multivariate analysis showed that the presence of nosocomial infection and neurologic symptoms were statistically significant predictors of inferior OS (P = .034 and P = .033, respectively).

Conclusion: In this series of adults with HLH, patients with nosocomial infections and neurologic symptoms had a statistically significant worse OS. In the largest series in Latin America, the most common cause of HLH was T-cell lymphoma. In our population, NM-HLH presented a higher mortality.
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http://dx.doi.org/10.1016/j.clml.2018.06.014DOI Listing
October 2018

Splenic myeloid metaplasia in warm autoimmune hemolytic anemia (wAIHA): a retrospective study.

Blood Res 2018 Mar 27;53(1):35-40. Epub 2018 Mar 27.

Hematology and Oncology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, México City, México.

Background: Splenic myeloid metaplasia (SMM) is a kind of extramedullary hematopoiesis, whereas its clinical significance in wAIHA remains unclear. The aim of this study is evaluating the frequency and clinical characteristics of SMM, compared with splenic-congestion (SC).

Methods: We included patients with wAIHA treated in a Mexican tertiary hospital between January 1992 and December 2015. All patients received steroids as first-line treatment and splenectomy as second-line treatment.

Results: Among the thirty-six splenectomized patients, 15 (41.6%) and 21 (58.4%) were diagnosed as SMM and SC, respectively. No differences were found in clinical characteristics between two groups. SMM patients showed lower platelet count (147×10/L vs. 240×10/L, =0.02) and higher presence of anti-dsDNA antibodies (40% vs. 4.7%, =0.01) than SC patients. Although the complete response (CR) rate with first-line treatment was lower in SMM patients (13.3% vs. 47.6%; =0.04), post-splenectomy median disease-free-survival (DFS) was longer (16.2 mo vs. 5.1 mo; =0.19). Univariate/multivariate analysis showed that achieving CR during first-line treatment (OR 0.3, 95% CI: 0.03-0.94, =0.03) and higher platelet count (OR 0.99, 95% CI: 0.98-0.99, =0.03) were protective factors for SMM; and anti-dsDNA titer higher than 9.6 IU/dL was a risk factor for SMM (OR 2.76, 95% CI: 1.48-5.14, <0.001).

Conclusion: The wAIHA patients with SMM have different biological profiles with those without SMM. This study is the first trial evaluating the significance of histopathological spleen findings and their association with rheumatologic profile.
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http://dx.doi.org/10.5045/br.2018.53.1.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898992PMC
March 2018

Blastic Transformation in Mexican Population With Chronic Myelomonocytic Leukemia.

Clin Lymphoma Myeloma Leuk 2017 08 24;17(8):532-538. Epub 2017 Jun 24.

Department of Hematology-Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Background: Chronic myelomonocytic leukemia (CMML) is the most aggressive of chronic leukemias, with short overall survival and a high transformation rate to acute leukemia. We investigated the factors related to blastic transformation in a Mexican population treated at a tertiary referral center.

Patients And Methods: The records of patients with a diagnosis of CMML from 2000 to 2015 were reviewed. A total of 54 patients were included, with a median age of 71 years and an overall survival of 16 months. The patients with incomplete data were excluded. IBM SPSS Statistics, version 21.0, software was used to perform the statistical analysis.

Results: The rate of blastic transformation was 33% (18 patients), and the interval time to progression was 9 months (range, 0-87 months). Comparing the patients who did not undergo blastic transformation to those who did, those with progression to acute leukemia tended to be younger (age, 58 vs. 71 years; P = .001), to have a greater peripheral blood blast count (≥ 2% vs. 0%; P = .003), and were more likely to have immature myeloid precursors circulating in the peripheral blood (94% vs. 64%; P = .02). On multivariate analysis, younger age continued to be a statistically significant factor for progression (hazard ratio, 0.97; 95% confidence interval, 0.929-0.987).

Conclusion: Mexican patients with CMML that progressed to overt acute leukemia were considerably younger, with a higher tumor burden and short overall survival. In this population, it is important to consider more aggressive treatment at diagnosis, focusing on high-dose chemotherapy and hematopoietic stem cell transplantation within a short period.
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http://dx.doi.org/10.1016/j.clml.2017.06.029DOI Listing
August 2017

Fluorescent In Situ Hybridization Monitoring and Effect of Detected Early Responses in the Outcome of Patients With Chronic Phase Chronic Myeloid Leukemia: A Report From a Latin American Country.

Clin Lymphoma Myeloma Leuk 2016 08 5;16(8):453-9. Epub 2016 May 5.

Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, México. Electronic address:

Introduction: The cytogenetic hallmark of chronic myeloid leukemia (CML) is the Philadelphia chromosome. Monitoring the response in patients receiving therapy is a standard of care. The present study was conducted to assess the monitoring adherence and reliableness of fluorescent in situ hybridization (FISH) as a monitoring tool and the effect of a complete cytogenetic response (CCyR) assessed by FISH on the prognosis of patients in a chronic phase (CP)-CML cohort.

Materials And Methods: We retrospectively analyzed the data from 63 newly diagnosed CP-CML patients treated with imatinib mesylate at a dose of 400 mg/day as frontline therapy. The clinical data and cytogenetic test results at diagnosis and during monitoring were collected. The cytogenetic monitoring adherence assessment rates were measured. A correlation between chromosome banding analysis (CBA) and FISH was performed. The CCyR assessed by FISH was defined as < 1% BCR-ABL1(+) nuclei. The Kaplan-Meier method was used for overall survival analysis and time-to-event estimates.

Results: The cytogenetic monitoring assessment adherence was 50.8% at 3 months, 93.5% at 6 months, 96.7% at 12 months, and 88.6% at 18 months. The Pearson correlation coefficient showed a significantly positive association (r = 0.84; P < .001) between CBA and FISH. The median follow-up duration after imatinib mesylate initiation was 60 months. A CCyR was achieved in 90.4% of patients within the first 18 months of therapy. At 3 months, 31 patients underwent a FISH evaluation, and 13 (41.9%) had achieved a CCyR. The patients who did not achieve a CCyR at 3 months had a significantly inferior probability of 5-year failure-free survival (38% vs. 94%; P = .001) and progression-free survival (80% vs. 100%; P = .043) compared with those with a CCyR.

Conclusion: We found improved monitoring adherence compared with the previous reports of Latin American populations. In countries with a high incidence of failure for CBA and a lack of real-time polymerase chain reaction standardization, FISH is a sensitive monitoring tool. In our cohort, patients not achieving an early CCyR, as tested by FISH, were a poor prognosis subgroup with worse rates of failure-free survival and progression-free survival.
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http://dx.doi.org/10.1016/j.clml.2016.04.002DOI Listing
August 2016

Prognostic Factors, Response to Treatment, and Survival in Patients With Chronic Myeloid Leukemia in Blast Phase: A Single-Institution Survey.

Clin Lymphoma Myeloma Leuk 2015 Dec 30;15(12):778-84. Epub 2015 Sep 30.

Chronic Leukemia Clinic, Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, México. Electronic address:

Introduction: Data from 51 patients (23 women) with chronic myeloid leukemia (CML) in blast phase (BP) were analyzed in order to identify prognostic factors for complete hematologic response (CHR) and survival.

Patients And Methods: Forty-four patients experienced disease progression from chronic or accelerated phase, and 7 cases presented as CML-BP. Thirteen patients (25.5%) had extramedullary involvement at diagnosis, and 71% were myeloid BP. Clonal evolution was identified in 53% of the cases, and the abnormalities most frequently observed were isochromosome (17q), double Philadelphia chromosome, and trisomy 8. Forty-five patients received treatment: 60% chemotherapy (CT) alone and 40% CT plus tyrosine kinase inhibitors (TKI) or TKI alone; 42% of them experienced CHR.

Results: Median overall survival (OS) in patients whose disease responded to treatment was 7 months (95% confidence interval, 1.7-6.2 months), with a median disease-free survival of 5 months (95% confidence interval, 2.8-5.8 months). One out of 3 patients who underwent hematopoietic stem-cell transplantation remains alive. Multivariate analysis revealed that lymphoid BP and TKI therapy had a statistically significant positive impact as prognostic factors for CHR. In the multivariate analysis, age > 60 years, hemoglobin < 10 g/dL, and complex karyotype were statistically significant negative prognostic factors for OS. There was no statistical significant difference in OS between patients who received only CT (1988-2002) with those treated with CT plus TKI (2003-2013).

Conclusion: This is the first study in Mexico to report prognostic factors associated with CHR and OS in patients with CML-BP.
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http://dx.doi.org/10.1016/j.clml.2015.09.007DOI Listing
December 2015

[Actual aspects of chronic myeloid leukemia].

Rev Invest Clin 2012 Mar-Apr;64(2):192-8

Departamento de Hematología y Oncología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, DF.

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October 2012
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