Browsing by Author "Rojas, Patricio"
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- ItemAcute myeloblastic leukemia in Chile: treatment and outcomes in patients admitted at the Hospital Clinico de la Pontificia Universidad Católica de Chile between 2010–2014(2014) Fuentes Arismendi, Mónica Paulina; Rojas, Patricio; Ernst Díaz, Daniel Matías; Acevedo Claros, Francisco Nicolás; Sarmiento Maldonado, Mauricio; Ocqueteau Tacchini, Mauricio Esteban; Bertin Cortes-Monroy, Pablo Alfonso; Ramírez, PabloIntroduction: Acute Myeloblastic Leukemia (AML) is the most frequent acute leukemia in the adults and its incidence increases with age. There are few studies about the demography and outcomes of AML patients in Chile and the only report belongs to a public hospital from 2000. We discuss the results of patients treated in our institution with AML non promyelocytic. Patients and Methods: Retrospective analysis of the epidemiologic, clinical and laboratory characteristics of diagnosis (cytology and flow cytometry) and treatment of AML non promyelocytic patients between 2010-2014. Statistical analysis of the data was performed using SPSS Statistics v21 software. Results: 63 patients were diagnosed with AML non M3, 52 males (66%), with a median age of 55.4 years (range: 16 - 89). Diagnosis laboratory tests (mean values and ranges) were: WBC 45.989/mm3 (range: 700 - 405.000); hemoglobin 9,1 g/dl (range: 5,2 - 14,1); platelets 75.548/mm3 (range: 10.000 - 454.000); peripheral blood blasts 38% (range 0 - 100); bone marrow blasts 74% (range 25 - 100%). The cytogenetic risk groups were: favorable (n=5, 8%), intermediate (n=33, 52%), adverse (n=8, 13%) and unknown (n=17, 27%). Of all the patients, 75% (n=47) received induction chemotherapy (CT) and 25% (n=16) palliative care. The mean age of the group with cytogenetic analysis was 51.2 years and only 8.6% did not receive consolidation CT. On the other hand, the group of patients with unknown cytogenetics had a mean age of 68 years and 57% did not receive consolidation CT. The mean survival of the CT group was 27.3 month (range: 0 - 53). By contrast, the mean survival in the palliative care group was 1 month (range: 0 - 6). The mean follow up in all patients was 13 months, (range: 1 - 55) and 17 months (range: 1 - 54) in the group that received CT. 87% (n=41) of patients with CT had febrile neutropenia with respiratory and intestinal focus most commonly identified. The induction mortality was 4,2% (n=2). Complete cytologic remission was achieved in 70% (n=33). The 3-year relapse free survival (RFS) and overall survival (OS) in the CT group were 25% and 31%, respectively. The multivariate survival analysis using Cox’s regression demonstrated that the variables that had significant impact in RFS and OS were: age at diagnosis (<60 years), achievement of disease remission and the use of induction and consolidation CT (high dose cytarabine versus others). In this analysis the cytogenetic risk did not have any impact in OS. The patients that only had induction CT (but not consolidation) had significantly better survival rates compared to the group in palliative care (6 months vs. 1 month, respectively, p=0.001). The mortality during the follow up of patients who had survived the induction CT was 47% (n=22), 2/3 of leukemia and 1/3 of infections. Conclusions: Our study shows that in our center, CR rates and OS rates after induction and consolidation chemotherapy are similar to those reported in international series, and are better than the data that was previously reported in our country. Low induction CT mortality, and the efficacy of CT in patients younger than 60 years old stand out in our report and validate the efficacy of intensive CT.
- ItemAutologous Stem Cell Transplant in Lymphoma Using a Noncryopreserved Platform: An Adapted Sequential Conditioning Maintaining Dose Intensity Does not Affect Transplantation Outcomes(2023) Sarmiento, Mauricio; Rojas, Patricio; Gutierrez, Catherine; Quezada, Jacqueline; Jara, Veronica; Campbell, James; Maria, Garcia; Jose, Max; VicenteSandoval; Vergara, Max; Triantafilo, Nicolas; Ocqueteau, MauricioThis retrospective study shows the feasibility of performing autologous stem cell transplantation in lymphoma using a non-cryopreserved strategy with conventional conditionings administered in fewer days. In a cohort of 61 patients, benefits of avoiding DMSO cryopreservation were observed. Background: Hematopoietic autologous stem cell transplantation (ASCT) is a validated therapeutic strategy for lymphoma treatment and precise well-tolerated conditioning. Several conditioning methods are available, but the most commonly used are CVB, BEAM, and ICE, which are conventionally administered in 6 to 7 days. Since 2015, our program has moved toward noncr yopreser ved platforms that require concise times; therefore, we have modified the conditioning by reducing it to 4 to 5 days. In this study, we show our experience. Methods: We compared ASCT performed in our program before and after 2015 in lymphoma patients. Between 2000 and 2014 and from 2015 to 2022, we performed 46 and 61 ASCT procedures, respectively. Results: Since 2015, we observed a greater number of infused stem cells, fewer episodes of febrile neutropenia (60% vs. 37% P = .008), shorter hospitalizations (30 vs. 18 days P = .001), faster engraftment (20 vs. 14 days P = .001) and better progression-free survival (72 vs. 44 months P = .002). Additionally, a prolonged overall survival was observed at these results, and this prolonged survival is difficult to interpret due to the short follow-up. Conclusion: In conclusion, conditioning adjusted for a noncryopreserved strategy offers at least similar or even better results than the cr yopreser ved strategy. Prospective studies are warranted.
- ItemIncreased morbidity and use of Primary Care medical services in patients with major depressive disorder and their families: A retrospective cohort study(EDICIONES DOYMA S A, 2012) Garcia Huidobro, Diego; Leon, Tomas; Vidal, Guillermo; Poblete, Fernando; Rojas, PatricioObjective: To study the impact of non-psychiatric medical visits by patients with Major Depressive Disorder (MDD) and their family members, compared to healthy people and their relatives in Primary Care.
- ItemProphylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma(2021) Caimi, Paolo F.; Pacheco Sanchez, Gabriela; Sharma, Ashish; Otegbeye, Folashade; Ahmed, Nausheen; Rojas, Patricio; Patel, Seema; Kleinsorge Block, Sarah; Schiavone, Jennifer; Zamborsky, Kayla; Boughan, Kirsten; Hillian, Antoinette; Reese-Koc, Jane; Maschan, Mikhail; Dropulic, Boro; Sekaly, Rafick-Pierre; De Lima, MarcosAnti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed/refractory lymphomas. Cytokine release syndrome (CRS) and immune effector cell - associated neurotoxicity syndrome (ICANS) are well-known complications. Tocilizumab, a monoclonal antibody targeting the interleukin-6 (IL-6) receptor was administered 1 hour prior to infusion of anti-CD19 CAR-T cells with CD3 zeta/4-1BB costimulatory signaling used to treat non-Hodgkin lymphoma patients. Relapsed/refractory lymphoma patients treated with anti-CD19 CAR-T cells were included in this analysis. Cytokine plasma levels were measured by electrochemiluminescence before lymphodepleting chemotherapy, prior to infusion and then on days 2, 4,6, and 14 days after treatment. Twenty patients were treated. Cell products included locally manufactured anti-CD19 CAR-T (n=18) and tisagenlecleucel (n=2). There were no adverse events attributed to tocilizumab. Ten patients had grade 1-2 CRS at a median of 4 (range 3-7) days. There were no cases of grade >= 3 CRS. Five patients had ICANS, grade 1 (n=4) and grade 4 (n=1). Laboratory studies obtained prior to lymphodepleting chemotherapy were comparable between patients with and without CRS, except for interleukin (IL)-15 plasma concentrations. patients with CRS had higher post-infusion ferritin and C reactive protein, with more marked increases in inflammatory cytokines, including IL-6, IL-15, IFN-gamma, fractalkine and MCP-1. Fifteen patients (75%) achieved CR and 2 (10%), PR. One-year OS and PFS estimates were 83% and 73%. Prophylactic tocilizumab was associated with low CRS incidence and severity. There were no adverse events associated with tocilizumab, no increase in frequency or severity of ICANS and excellent disease control and overall survival.
- ItemProphylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice(Elsevier B.V., 2024) Chandía Cristi, América Valeska; Gutiérrez García, Daniela A.; Dulcey, Andrés E.; Lara, Marcelo; Vargas Rojas, Lina Marcela; Lin, Yi-Han; Jiménez Muñoz, Pablo Salvador; Larenas Barrera, Gabriela Paz; Xu, Xin; Wang, Amy; Owens, Ashley; Dextras, Christopher; Chen, YuChi; Pinto, Claudio; Marín Marín, Tamara Alejandra; Almarza Salazar, Hugo Alcester; Acevedo, Keryma; Cancino Lobos, Gonzalo Ignacio; Hu, Xin; Rojas, Patricio; Ferrer, Marc; Southall, Noel; Henderson, Mark J.; Zanlungo Matsuhiro, Silvana; Marugan, Juan J.; Álvarez Rojas, AlejandraThe molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.
- ItemResultados en el tratamiento de pacientes con leucemia mieloide aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica entre los años 2010-2014(2015) Fuentes, Mónica; Rojas, Patricio; Ernst Diaz, Daniel Matias; Ocqueteau Tachini, Mauricio; Bertín Cortes Monroy, Pablo; Sarmiento Maldonado, Mauricio; Ramírez, Pablo
- ItemRuxolitinib for Severe COVID-19-Related Hyperinflammation in Nonresponders to Steroids(2021) Sarmiento, Mauricio; Rojas, Patricio; Jerez, Joaquin; Bertin, Pablo; Campbell, James; Garcia, Maria J.; Pereira, Jaime; Triantafilo, Nicolas; Ocqueteau, MauricioIntroduction: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. Methods: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. Results: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005). Conclusion: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.
- ItemSalud ósea en pacientes sometidos a trasplante de precursores hematopoyéticos: un nuevo problema a considerar(2016) Florenzano Valdés, Pablo Felipe; Ernst Diaz, Daniel Matias; Lustig, Nicole; Rojas, Patricio; Ramírez, Pablo; Campusano Montaño, Claudia