5 years DKMS Chile: approach, results and impact of the first unrelated stem cell donor center in Chile.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed worldwide to treat blood cancer and other life-threatening blood disorders. As successful transplantation requires an HLA-compatible donor, unrelated donor centers and registries have been established worldwide to identify donors for patients without a family match. Ethnic minorities are underrepresented in large donor registries. Matching probabilities are higher when donors and patients share the same ethnic background, making it desirable to increase the diversity of the global donor pool by recruiting donors in new regions. Here, we report the establishment and the first 5 years of operation of the first unrelated stem cell donor center in Chile, a high-income country in South America with a population of over 19 million. Methods: We used online and in-person donor recruitment practices through patient appeals and donor drives in companies, universities, the armed forces, and public services. After confirmatory typing donors were subjected to medical work-up and cleared for donation. Results: We recruited almost 170,000 donors in 5 years. There were 1,488 requests received for confirmatory typing and donor availability checks, of which 333 resulted in medical work-up, leading to 194 stem cell collections. Products were shipped to Chile (48.5%) and abroad. Even when the COVID-19 pandemic challenged our activities, the number of donors recruited and shipped stem cell products remained steady. In Chile there was an almost 8-fold increase in unrelated donor transplantation activity from 16 procedures in 2016-2018 to 124 procedures in 2019-2021, mainly for pediatric patients following the center's establishment. We estimate that 49.6% of Chilean patients would find at least one matched unrelated donor in the global DKMS donor pool. Discussion: Establishing a DKMS donor center in Chile has significantly increased donor availability for Chilean patients and contributed to an increase of unrelated donor stem cell transplant activity.

Increased incidence of rheumatoid arthritis after COVID-19.

An increase in the incidence of inflammatory arthritis after COVID-19 has been reported. Since many diseases exhibit population-specific causal effect sizes, we aimed to evaluate the incidence trends of inflammatory arthritis, including rheumatoid arthritis (RA), after COVID-19 in a large admixed Colombian population. Data analysis for this retrospective, population-based cohort study was carried out using the COOSALUD EPS registry. The following codes were selected for analyses: M059, seropositive RA, M069, unspecified RA, M060 seronegative RA, and other RA-related diagnoses: M064, M139, M068, M058, M130 and M053. The study period was limited to January 01, 2018, through December 31, 2022. Incidence rates (IRs) and incidence rate ratios (IRRs) were assessed. A Cox survival model was built to evaluate the influence of age, gender, and COVID-19 vaccination status on the development of inflammatory arthritis. A bioinformatic analysis was performed to evaluate the homology between SARS-CoV-2 and autoantigen peptides related to RA. The entire population study comprised 3,335,084 individuals. During the pandemic period (2020-2022) the total IIR for seropositive and unspecified RA were 1.60 (95% CI, 1.16-2.22) and 2.93 (95% CI, 2.04-4.19), respectively, and the IIR for overall RA-related diagnosis was 2.01 (95% CI 1.59-2.53). The age groups hazard ratios (HRs) were increased until the age group of 51-60 years (HR: 9.16; 95% CI, 7.24-11.59) and then decreased slightly in the age group 61 years or older (HR: 5.364; 95% CI, 4.24-6.78) compared to those within 18-30 years. Men were less at risk than women to develop inflammatory arthritis (HR: 0.21; 95% CI, 0.18-0.24). The greater time since COVID-19 diagnosis was associated with a lower likelihood of developing inflammatory arthritis (HR: 0.99; 95% CI:0.998-0.999). Vaccination (all types of COVID-19 vaccines included) did not prevent the development of inflammatory arthritis after COVID-19. Low identity was found between the SARS-CoV-2 ORF1ab antigen and the human antigens Poly ADP-ribose polymerase 14 and Protein mono-ADP-ribosyltransferase PARP9 isoform D (39% and 29%, respectively). In conclusion, our study confirms increased incidence of inflammatory arthritis, including RA, after COVID-19, with the greatest increase occurring before the first year post-covid. Women in their fifties were more susceptible. Further research is required to examine the effectiveness of vaccination in preventing post-COVID inflammatory arthritis and the mechanisms implicated in the development of RA after COVID-19.

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.

SARS-CoV-2 vaccine booster in solid organ transplant recipients previously immunised with inactivated versus mRNA vaccines: A prospective cohort study.

Background: Solid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine. Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses. Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P = 0.035) and NAb positivity (77.4% vs 55.1%, P = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups. Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster. Funding: School of Medicine, UC-Chile and ANID.ClinicalTrials.gov ID: NCT05124509.

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.

Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile.

BACKGROUND: Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. METHODS: This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. RESULTS: NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. CONCLUSIONS: Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients. CLINICAL TRIALS REGISTRATION: NCT04888793.

[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.

A real life use of ruxolitinib in patients with acute and chronic graft versus host disease refractory to corticosteroid treatment in Latin American patients

Abstract Introduction: Graft-versus-host disease (GVHD) is a serious complication in allogeneic transplantation. The first-line treatment is high doses of corticosteroids. In the absence of response to corticosteroids, several immunosuppressive drugs can be used, but they entail an elevated risk of severe infections. Added to this, there are patients who do not improve on any immunosuppressive treatment, with subsequent deteriorated quality of life and high mortality. Ruxolitinib has been shown to induce responses in refractory patients. In this study we have presented our real-life experience. Methods: A retrospective analysis was performed on patients with severe GVHD refractory to corticosteroids. Demographic, previous treatment, response and mortality data were collected. Results: Since 2014, seventeen patients with GVHD were treated with ruxolitinib due to refractoriness to corticosteroids and immunosuppressants and a few to extracorporeal photopheresis, 8 with acute GVHD (1 pulmonary, 4 cutaneous grade IV and 3 digestive grade IV) and 9 with chronic GHVD (5 cutaneous sclerodermiform, 2 pulmonary and 1 multisystemic). The overall response to ruxolitinib treatment for acute GVHD was 80%, 40% with partial response and 40% with complete remission. Global response in chronic GVHD was 79%. The GVHD mortality was only seen in acute disease and was 40%. Causes of mortality in those patients were severe viral pneumonia, post-transplantation hemophagocytic syndrome and meningeal GVHD refractory to ruxolitinib. Conclusions: In our series, the use of ruxolitinib as a rescue strategy in acute or chronic GVHD was satisfactory. Ruxolitinib treatment in patients with a very poor prognosis showed encouraging results. However, the GVHD mortality remains high in refractory patients, showing that better therapeutic strategies are needed.

[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.

Síndrome hematofagocítico como manifestación inicial de linfoma de Hodgkin clásico / Hemophagocytic syndrome as the initial manifestation of Hodgkin lymphoma

Introducción: las histiocitosis son un grupo heterogéneo de enfermedades; una de ellas es el síndrome hematofagocítico (SHF). Sus causas pueden ser infecciosas, neoplásicas, autoinmunes o relacionadas a inmunodeficiencias adquiridas; el linfoma de Hodgkin clásico (LHc) es una causa poco frecuente. Se reporta el caso de un hombre inmunodeprimido de 35 años que ingresa al hospital febril y con insuficiencia respiratoria grave.Métodos: se recopiló información clínica pertinente y se revisó material de biopsia estudiado con tinción de hematoxilina ­ eosina, técnica inmunohistoquímica e hibridación in situ cromogénica. Resultados: estudios de laboratorio muestran pancitopenia, altera-ción de pruebas hepáticas, hipertrigliceridemia, hipoalbuminemia e hiperferritinemia. El estudio de médula ósea hematopoyética con mielograma y biopsia muestran hallazgos compatibles con LHc, signos de hemofagocitosis e infección por virus Epstein-Barr (VEB). Se diagnostica SHF como primera manifestación de LHc e infección por VEB. Conclusiones: a la fecha, se describen 74 pacientes re-portados con SHF como manifestación de LHc; en el 84% fue su primera manifestación. Si bien la presentación clínica presentada es infrecuente, se ha propuesto una asociación en hombres con inmunodeficiencia, SHF, LHc e infección por VEB; por lo que se sugiere una sospecha diagnóstica alta.

Introduction: histiocytosis are a heterogeneous group of diseases; one of them is the hemophagocytic syndrome (HS). Its causes can be infectious, neoplastic, autoimmune or related to acquired immunodeficiencies; classic Hodgkin lymphoma (cHL) is a rare cause.We present the case of an immunosuppressed 35-year-old male who was admitted with fever and acute respiratory failure. Methods:pertinent clinical reports and biopsy material were reviewed; including hematoxylin-eosin stained slides from formalin-fixed and pa-raffin-embedded tissue blocks and immunohistochemical and chromogenicin situhybridisation studies. Results:laboratory studies revealed pancytopenia, abnormal liver functions, hypertriglyceridemia, hypoalbuminemia e hyperferritinemia. Bone marrow aspiration smear and biopsy showed a malignant lymphoid neoplasm consistent with cHL, signs of hemophagocytosis, and Epstein-Barr virus (EBV) infection. HS, as an initial manifestation of cHL, was diagnosed.Conclusions:to our best knowledge, there are 74 reported cases of cHL with HS; in 84% it was the initial clinical manifestation. Though this is an unusual presentation, an association between immu-nodeficiency, HS, cHL, and EBV infection has been proposed; so a high diagnostic suspicion is suggested.

Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial.

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.

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.

JAK/STAT Pathway Inhibition May Be a Promising Therapy for COVID-19-Related Hyperinflammation in Hematologic Patients.

COVID-19 has rapidly become a major concern for the health systems worldwide. Its high contagiousness and associated mortality demand the discovery of helpful interventions with promising safety profile. Here, we report 3 severe COVID-19 cases, which achieved rapid and sustained improvement in outcome with the use of ruxolitinib, a JAK/STAT pathway inhibitor.

A real life use of ruxolitinib in patients with acute and chronic graft versus host disease refractory to corticosteroid treatment in Latin American patients.

INTRODUCTION: Graft-versus-host disease (GVHD) is a serious complication in allogeneic transplantation. The first-line treatment is high doses of corticosteroids. In the absence of response to corticosteroids, several immunosuppressive drugs can be used, but they entail an elevated risk of severe infections. Added to this, there are patients who do not improve on any immunosuppressive treatment, with subsequent deteriorated quality of life and high mortality. Ruxolitinib has been shown to induce responses in refractory patients. In this study we have presented our real-life experience. METHODS: A retrospective analysis was performed on patients with severe GVHD refractory to corticosteroids. Demographic, previous treatment, response and mortality data were collected. RESULTS: Since 2014, seventeen patients with GVHD were treated with ruxolitinib due to refractoriness to corticosteroids and immunosuppressants and a few to extracorporeal photopheresis, 8 with acute GVHD (1 pulmonary, 4 cutaneous grade IV and 3 digestive grade IV) and 9 with chronic GHVD (5 cutaneous sclerodermiform, 2 pulmonary and 1 multisystemic). The overall response to ruxolitinib treatment for acute GVHD was 80%, 40% with partial response and 40% with complete remission. Global response in chronic GVHD was 79%. The GVHD mortality was only seen in acute disease and was 40%. Causes of mortality in those patients were severe viral pneumonia, post-transplantation hemophagocytic syndrome and meningeal GVHD refractory to ruxolitinib. CONCLUSIONS: In our series, the use of ruxolitinib as a rescue strategy in acute or chronic GVHD was satisfactory. Ruxolitinib treatment in patients with a very poor prognosis showed encouraging results. However, the GVHD mortality remains high in refractory patients, showing that better therapeutic strategies are needed.

Perspectiva hematológica en el tratamiento de pacientes con COVID-19: rol de los tratamientos antiinflamatorios

The pathophysiology of the inflammatory profile induced by SARS-COV2 infection has similarities with conditions of immune system activation with cytokine release such as hemophagocytic syndrome and some cases of acute graft-versus-host disease. There are encouraging results of clinical studies, performed with increasingly better methodological quality, supporting the use of targeted and specific anti-inflammatory therapy in selected groups of patients with COVID-19 with severe inflammation. In this review we describe the inflammatory pathophysiology of the disease and the recent findings about its treatment.

Haploidentical transplantation outcomes are comparable with those obtained with identical human leukocyte antigen allogeneic transplantation in Chilean patients with benign and malignant hemopathies

Abstract Introduction Patients with benign or malignant blood disorders, who require allogeneic stem cell transplantation and lack an identical human leukocyte antigen HLA identicalHL sibling donor, could be transplanted with hematopoietic stem cells from unrelated adult or umbilical cord donors. However, in our country, both approaches are costly and time-consuming options. Methods Over the last few years, haploidentical modalities have been investigated as an alternative donor source, showing similar results to those obtained with identical HLA donors. We started using T-cell-replete haploidentical with post-transplant cyclophosphamide in 2012 and we presented our experience with patients undergoing haploidentical ransplantation compared to SIB. Results Since January 2012 to date, 91 allogeneic transplants have been performed, of which 49 were haploidentical and 42 were HLA identical. The mean age of the patients was 35 years (range: 17-62). The mean CD34/kg × 106 infused per group was 5.93 and 5.89, respectively. Time to granulocyte and platelet engraftment was 11 and 15 days, respectively, for haploidentical, and 12 and 14 days, respectively, for HLA identical (p = 0.10). The 100-day cumulative incidence of global acute GVHD was 34% for haploidentical and 29% for SIHLA identical (p = 0.9). The 2-year overall global graft-versus-host disease was 43% for haploidentical and 41% for HLA identical (p = 0.8). Overall survival, relapse, and transplant and relapse-related mortality were similar between both groups. Conclusion Our experience showed that haploidentical has similar outcomes to those obtained with HLA idential and can be performed in our country safely.

Haploidentical transplantation outcomes are comparable with those obtained with identical human leukocyte antigen allogeneic transplantation in Chilean patients with benign and malignant hemopathies.

INTRODUCTION: Patients with benign or malignant blood disorders, who require allogeneic stem cell transplantation and lack an identical human leukocyte antigen HLA identicalHL sibling donor, could be transplanted with hematopoietic stem cells from unrelated adult or umbilical cord donors. However, in our country, both approaches are costly and time-consuming options. METHODS: Over the last few years, haploidentical modalities have been investigated as an alternative donor source, showing similar results to those obtained with identical HLA donors. We started using T-cell-replete haploidentical with post-transplant cyclophosphamide in 2012 and we presented our experience with patients undergoing haploidentical ransplantation compared to SIB. RESULTS: Since January 2012 to date, 91 allogeneic transplants have been performed, of which 49 were haploidentical and 42 were HLA identical. The mean age of the patients was 35 years (range: 17-62). The mean CD34/kg×106 infused per group was 5.93 and 5.89, respectively. Time to granulocyte and platelet engraftment was 11 and 15 days, respectively, for haploidentical, and 12 and 14 days, respectively, for HLA identical (p=0.10). The 100-day cumulative incidence of global acute GVHD was 34% for haploidentical and 29% for SIHLA identical (p=0.9). The 2-year overall global graft-versus-host disease was 43% for haploidentical and 41% for HLA identical (p=0.8). Overall survival, relapse, and transplant and relapse-related mortality were similar between both groups. CONCLUSION: Our experience showed that haploidentical has similar outcomes to those obtained with HLA idential and can be performed in our country safely.

[Anti-inflammatory therapies for SARS-COV2 infection from a hematological perspective]. / Perspectiva hematológica en el tratamiento de pacientes con COVID-19: rol de los tratamientos antiinflamatorios.

The pathophysiology of the inflammatory profile induced by SARS-COV2 infection has similarities with conditions of immune system activation with cytokine release such as hemophagocytic syndrome and some cases of acute graft-versus-host disease. There are encouraging results of clinical studies, performed with increasingly better methodological quality, supporting the use of targeted and specific anti-inflammatory therapy in selected groups of patients with COVID-19 with severe inflammation. In this review we describe the inflammatory pathophysiology of the disease and the recent findings about its treatment.

[Results of acute myeloid leukemia treatment. Analysis of 63 patients between 2010-2014]. / Resultados 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.

BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, emphasizing its high recurrence rate despite hematopoietic cell transplantation (HCT). AIM: To report the results of AML treatment at the Catholic University of Chile Clinical Hospital. PATIENTS AND METHODS: Review of medical records of patients with AML. RESULTS: 63 patients, median age 55.4 years (range:16-89), treated between 2010 and 2014. Admission laboratory values showed (median values): leukocytes 45.989/mm³, hemoglobin 9.1 g/dl, platelets 75.548/mm³, peripheral blood blasts 38% and bone marrow blasts 74%. According to cytogenetic risk classification we observed the following groups: favorable 8% (n = 5), intermediate 51% (n = 32), unfavorable 13% (n = 8) and unknown 28% (n = 17). Seventy five percent of patients received induction chemotherapy and 25% palliative care. Median survival of treated and palliative care patients was 27.3 and 1 month respectively. Induction chemotherapy (IC) mortality (ICM) was 4.2%. Seventy percent (n = 33) of patients who received IC had complete response (CR) with a 3-year relapse free survival (RFS) of 25% and overall survival (OS) of 31%. Multivariate analysis demonstrated that achievement of CR, cytogenetic risk group and receiving consolidation chemotherapy were significantly associated with better RFS and OS. CONCLUSIONS: AML treatment with standard chemotherapy in our center achieves similar results to what has been described in international series regarding induction rates and ICM, however RFS and OS are still very low, especially in intermediate and high cytogenetic risk groups.