Autologous Stem Cell Transplant in Lymphoma Using a Noncryopreserved Platform: An Adapted Sequential Conditioning Maintaining Dose Intensity Does not Affect Transplantation Outcomes.

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 noncryopreserved 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 cryopreserved strategy. Prospective studies are warranted.

Actualización de resultados demográficos y terapéuticos de pacientes con Leucemia Mieloide Aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica de Chile / Acute myeloid leukemia. Analysis of 114 patients

BACKGROUND: Acute myeloid leukemia (AML) is the most common leukemia in adults. Aim: To Describe our population of patients with AML and report the outcomes of our treatments. MATERIAL AND METHODS: Review of electronic clinical records of 114 patients with AML with a median age of 57 years (59% men). Results: Seventeen percent of patients were classified as low risk, 38% as intermediate risk and 33% as high risk. Seventy-six percent of patients were treated with intensive chemotherapy. Five years overall survival according to cytogenetic risk was 59, 41, and 12% in low, intermediate, and high-risk patients, respectively. The outcomes were better in patients under 60 years. The median survival of patients treated with intensive chemotherapy aged less than 60 years and 60 years and above was 3.4 and 1 year, respectively. CONCLUSIONS: Our results are comparable to those reported in developed countries. Improving the survival of patients 60 years and older is our main challenge.

[Acute myeloid leukemia. Analysis of 114 patients]. / Actualización de resultados demográficos y terapéuticos de pacientes con Leucemia Mieloide Aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica de Chile.

BACKGROUND: Acute myeloid leukemia (AML) is the most common leukemia in adults. AIM: To Describe our population of patients with AML and report the outcomes of our treatments. MATERIAL AND METHODS: Review of electronic clinical records of 114 patients with AML with a median age of 57 years (59% men). RESULTS: Seventeen percent of patients were classified as low risk, 38% as intermediate risk and 33% as high risk. Seventy-six percent of patients were treated with intensive chemotherapy. Five years overall survival according to cytogenetic risk was 59, 41, and 12% in low, intermediate, and high-risk patients, respectively. The outcomes were better in patients under 60 years. The median survival of patients treated with intensive chemotherapy aged less than 60 years and 60 years and above was 3.4 and 1 year, respectively. CONCLUSIONS: Our results are comparable to those reported in developed countries. Improving the survival of patients 60 years and older is our main challenge.

[Age does not affect the outcome of allogeneic hematopoietic precursor transplantation for acute myeloid leukemia]. / Resultados a largo plazo de una cohorte chilena: la edad del paciente no incide en el resultado del trasplante alogénico de precursores hematopoyéticos para leucemia mieloide aguda.

BACKGROUND: In our country, transplantation centers differ in the age limit for allogeneic hematopoietic transplantation (ALOHT). In our program, transplants with age- adjusted conditioning are performed in patients until 70 years old. Currently more than 60% of ALOHT reported to the Center for International Bone Marrow Transplantation Research (CIBMTR) are performed in patients older than 40 years. AIM: To report our experience with ALOHT in acute myelogenous leukemia (AML), analyzing patient age at transplantation in different periods and transplant results in different age groups. MATERIAL AND METHODS: A retrospective analysis of the database of adult hematopoietic transplants in AML patients was performed. Demographic data, disease characteristics, transplant data, survival and relapse times, and mortality were collected. RESULTS: In our program, 1030 transplants were performed in adults and 119 ALOHT were performed in AML patients, between 1990 and 2020. The median age of patients in all periods was 41 years, (range 16-69). The median age was 33 and 45 years, in the periods 1990-2000 and 2000-2020 respectively (p < 0.01). Seventy-eight patients received myeloablative conditioning (median age 44 years) and 41 reduced intensity conditioning (median age 53 years). Five-year overall survival was 44.6% (confidence intervals (CI) 41-48). Non relapse mortality of all periods was 19% (CI 17 - 40%) and relapse rate was 17 % (CI 16-22). No difference in five years overall survival among patients younger than 40, 41 to 50 and over 51 years was observed. CONCLUSIONS: Overall Survival, non-relapse mortality and relapse rate were similar in younger and older patients in our program and similar to those previously reported in other centers.

Ruxolitinib for Severe COVID-19-Related Hyperinflammation in Nonresponders to Steroids.

INTRODUCTION: 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.

Mineralocorticoid receptor modulation by dietary sodium influences NAFLD development in mice.

INTRODUCTION AND OBJECTIVES: Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD. MATERIALS AND METHODS: C57BL/6J mice were fed either a high-fat-diet (HFD) or a choline/methionine deficient (MCD) diet with different sodium concentrations. Hepatic concentration of lipid species, serum aldosterone levels, expression of MR, proinflammatory and profibrotic markers and liver histology were assessed. RESULTS: Mice fed with High-Na+/HFD showed a lower MR expression in liver (p = 0.01) and less steatosis on histology (p = 0.04). Consistently, animals from this group exhibited lower levels of serum aldosterone (p = 0.028) and lower hepatic triglyceride content (p = 0.008). This associated to a reduced expression of lipogenic genes, significant changes in lipid subspecies, lower HOMA-IR (p < 0.05), and lower expression of pro-inflammatory and profibrotic markers compared to those mice fed a Low-Na+/HFD. Additionally, mice fed a High-Na+/HFD showed higher expression of salt-inducible kinase (SIK)-1 and lower expression of serum-and-glucocorticoid-inducible kinase (SGK)-1. Similar results were observed with the MCD diet model. CONCLUSION: We identified in two experimental models of NAFLD that High-Na+ diet content is associated to lower serum aldosterone levels and hepatic MR downregulation, associated to decreased steatosis and reduced de novo hepatic lipogenesis, proinflammatory and profibrotic markers. Decreased activation of hepatic MR seems to generate beneficial downstream inhibition of lipogenesis in experimental NAFLD.

Resultados a largo plazo de una cohorte chilena: la edad del paciente no incide en el resultado del trasplante alogénico de precursores hematopoyéticos para leucemia mieloide aguda

Background: In our country, transplantation centers differ in the age limit for allogeneic hematopoietic transplantation (ALOHT). In our program, transplants with age- adjusted conditioning are performed in patients until 70 years old. Currently more than 60% of ALOHT reported to the Center for International Bone Marrow Transplantation Research (CIBMTR) are performed in patients older than 40 years. Aim: To report our experience with ALOHT in acute myelogenous leukemia (AML), analyzing patient age at transplantation in different periods and transplant results in different age groups. Material and Methods: A retrospective analysis of the database of adult hematopoietic transplants in AML patients was performed. Demographic data, disease characteristics, transplant data, survival and relapse times, and mortality were collected. Results: In our program, 1030 transplants were performed in adults and 119 ALOHT were performed in AML patients, between 1990 and 2020. The median age of patients in all periods was 41 years, (range 16-69). The median age was 33 and 45 years, in the periods 1990-2000 and 2000-2020 respectively (p < 0.01). Seventy-eight patients received myeloablative conditioning (median age 44 years) and 41 reduced intensity conditioning (median age 53 years). Five-year overall survival was 44.6% (confidence intervals (CI) 41-48). Non relapse mortality of all periods was 19% (CI 17 - 40%) and relapse rate was 17 % (CI 16-22). No difference in five years overall survival among patients younger than 40, 41 to 50 and over 51 years was observed. Conclusions: Overall Survival, non-relapse mortality and relapse rate were similar in younger and older patients in our program and similar to those previously reported in other centers.

Asociación entre enfermedad de von Willebrand y angiodisplasia: ¿casualidad o causalidad?

Von Willebrand factor (vWf) is a fundamental multimeric plasma glycoprotein in the coagulation process. Its function is to mediate platelet adhesion and to stabilize circulating factor VIII. A functional or quantitative alteration of vWf gives rise to von Willebrand disease (vWD). The association between vWD and angiodysplasia was described in 1967, but it was only until 2011 that Starke et al demonstrated the in vitro and in vivo role of vWf in angiogenesis. Congenital or acquired vWf deficiency, especially of high molecular weight multimeters, not only favors bleeding, but also contributes to increased angiogenesis in these patients. The treatment should be focused both on the control of the acute episode of gastrointestinal bleeding, with vWf replacement therapy and local endoscopic treatment, as well as on the prevention of the progression of angiodysplasia and future bleeding. There are different published therapeutic approaches using vWf replacement that are not effective in all patients. Recently, angiogenesis inhibitor medications have been used.

[Association between von Willebrand disease and angiodysplasia]. / Asociación entre enfermedad de von Willebrand y angiodisplasia: ¿casualidad o causalidad?

Von Willebrand factor (vWf) is a fundamental multimeric plasma glycoprotein in the coagulation process. Its function is to mediate platelet adhesion and to stabilize circulating factor VIII. A functional or quantitative alteration of vWf gives rise to von Willebrand disease (vWD). The association between vWD and angiodysplasia was described in 1967, but it was only until 2011 that Starke et al demonstrated the in vitro and in vivo role of vWf in angiogenesis. Congenital or acquired vWf deficiency, especially of high molecular weight multimeters, not only favors bleeding, but also contributes to increased angiogenesis in these patients. The treatment should be focused both on the control of the acute episode of gastrointestinal bleeding, with vWf replacement therapy and local endoscopic treatment, as well as on the prevention of the progression of angiodysplasia and future bleeding. There are different published therapeutic approaches using vWf replacement that are not effective in all patients. Recently, angiogenesis inhibitor medications have been used.

Concurrent nonalcoholic fatty liver disease and type 2 diabetes: diagnostic and therapeutic considerations.

Introduction: The relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) is complex and bidirectional. NAFLD increases the risk of incident diabetes and is very prevalent in T2DM patients and T2DM is an aggravating factor for NAFLD. Timely T2DM diagnosis and treatment in subjects with NAFLD and diagnosis, staging and treatment of NAFLD in those with T2DM are critical issues. Areas covered: PubMed/MEDLINE was searched for articles related to concomitant occurrence of NAFLD and T2DM between January 2013 and May 2019. Areas covered included epidemiological, diagnostic and therapeutic aspects. Expert opinion: there is a need for increased awareness on NAFLD adding liver disease as an end-organ complication of T2DM. Emphasis on use of simple non-invasive tools to triage patients with potentially severe liver disease should be made. Management of patients with NAFLD and T2DM relies on lifestyle optimization to achieve significant weight loss. Currently, there is no drug approved for treatment of NAFLD in patients with T2DM although Vitamin E and pioglitazone might be used in selected patients. Approved diabetic medications hold promise for NAFLD treatment and several liver-specific drugs are in evaluation clinical trials. A combination approach will likely represent the future of NAFLD therapeutics.

Cabergoline or bromocriptine for prolactinoma? / ¿Cabergolina o bromocriptina para el prolactinoma?

Cabergoline and bromocriptine are among the most commonly used drugs to treat prolactinoma. Cabergoline is a long-acting dopamine receptor agonist which might offer advantages over bromocriptine. However, it is not clear if this translates into clinical benefits. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including 12 studies addressing the question of this article, including five randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded cabergoline is more effective than bromocriptine in resolution of amenorrhea/oligomenorrhea and galactorrhea, it probably increases pregnancy rate, and it is associated to less adverse effects. It is not clear whether cabergoline is also more effective with respect to tumor growth because the certainty of the evidence is very low.

Cabergolina y bromocriptina son los fármacos más utilizados en el manejo del prolactinoma. Si bien cabergolina, un agonista dopaminérgico de vida media larga, tendría algunas ventajas desde el punto de vista fisiopatológico, no está claro si esto se traduce en un real beneficio. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos dos revisiones sistemáticas que en conjunto comprenden 12 estudios relevantes para la pregunta, incluyendo cinco estudios controlados aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que la cabergolina es superior a la bromocriptina en la mejoría de la oligomenorrea/amenorrea y la galactorrea, probablemente aumenta la probabilidad de embarazo, y se asocia a menos efectos adversos. No está claro si cabergolina también es más efectiva sobre el crecimiento del tumor porque la certeza de la evidencia es muy baja.

Erradicación de Helicobacter pylori para la trombocitopenia inmune: protocolo de una revisión sistemática / Eradication of Helicobacter pylori for immune thrombocytopenia: protocol of a systematic review

Introducción: La trombocitopenia inmune es una enfermedad caracterizada por destrucción plaquetaria mediada por anticuerpos. Se ha planteado que Helicobacter pylori podría actuar como gatillante y modulador de dicha enfermedad, por lo que el objetivo de esta revisión es evaluar si la erradicación de este agente podría constituir un tratamiento efectivo para la trombocitopenia inmune. Métodos: El protocolo fue diseñado, y será reportado, en línea con Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Se realizará una búsqueda de estudios controlados aleatorizados, que incluyan pacientes con trombocitopenia inmune y que hayan recibido terapia de erradicación para Helicobacter pylori. Los desenlaces a evaluar serán el sangrado, la mortalidad, la necesidad de esplenectomía, el incremento en el recuento plaquetario, entre otros. Realizaremos búsquedas sensibles en MEDLINE, CENTRAL y EMBASE, sin restricción por lenguaje o publicación, las cuales serán complementadas con búsquedas en otras fuentes. Al menos dos investigadores realizarán de manera independiente la selección de los estudios y la extracción de los datos. Se evaluará el riesgo de sesgo utilizando la herramienta recomendada por la colaboración Cochrane. Se realizará metanálisis y se presentarán los datos mediante el método GRADE. Fortalezas y debilidades: Esta revisión sistemática entregará una síntesis rigurosa y actualizada de los efectos de la erradicación de Helicobacter pylori en la trombocitopenia inmune. La principal limitación podría provenir de la baja revisión sistemática (PROSPERO): CRD42015022161.(AU)

Background: Immune Thrombocytopenia is a condition characterized by antibody-mediated platelet destruction. Helicobacter pylori has been postulated as a potential trigger or modulator in this disease, so Helicobacter pylori eradication has been proposed as a reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). We will conduct a search of randomized controlled trials, including patients with immune thrombocytopenia that received eradication therapy for Helicobacter pylori. The evaluated outcomes will be bleeding, mortality, need of splenectomy, platelet count, among others. We will develop sensitive search strategies for MEDLINE, EMBASE and CENTRAL, with no language or publication restriction. We will complement electronic searches with other sources. At least two reviewers will independently select trials and extract data. We will use Cochrane tool for risk of bias assessment to assess included studies. We will conduct meta-analysis and data will be presented using the GRADE approach. Strengths and limitations: This systematic review will provide a rigorous and updated summary of the effects of Helicobacter pylori eradication on immune thrombocytopenia. The main limitation might arise from the low quantity or quality of trials identified for this topic. Systematic review register number (PROSPERO): CRD42015022161(AU)