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.

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.

Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón / Allogenic hematopoietic stem cell transplantation with unrelated cord blood: Report of three cases from the Chilean cord blood bank

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Identificación y cuantificación del arsénico unido a las proteínas de tejidos cardiovasculares de pacientes sometidos a cirugía de revascularización coronaria / Identification and quantification of protein-linked arsenic in cardiovascular tissues from patients submitted to coronary revascularization

Introducción: Los efectos de la intoxicación con Arsénico (As) como enfermedades cardiovasculares (CV), pigmentaciones y oclusiones arteriales coronarias están asociados con la ingestión de As inorgánico a través del agua de bebida y a exposiciones ambientales. La unión del As (III) a proteínas y la metilación del As podría ser una primera etapa en el mecanismo de detoxificación. Objetivo: Evaluar la unión de As a proteínas en aurícula derecha y vena safena (VS) en sujetos expuestos de la Región de Antofagasta. Métodos: Se estudió la asociación As-proteína en el citosol de AD y VS de 6 pacientes con enfermedad coronaria grave de la Región de Antofagasta. Para el fraccionamiento del citosol se utilizaron columnas de exclusión molecular de tres diferentes rangos de masas. El perfil del As se detectó por Espectrometría de Masas Inductivamente Acoplado (ICP-MS) y por Espectrosco-pía Ultra Violeta - Visible de las fracciones moleculares (enlaces As- tiolatos de proteínas). Resultados: En todos los casos el As estuvo ampliamente distribuido en todo el intervalo de fracciones para AUD y VS. Los porcentajes de As colectado en las fracciones de las diferentes columnas usadas fueron 10, 25 y 50 por ciento. En la especiación de As en el citosol, por Cromatografía Líquida de Alta Resolución acoplada a la Espectrometría de Masas (IC-HPLC-ICP-MS), solamente se encontró As(III) y As(V) con una distribución Gaussiana para ambas especies, siendo la relación As(III)/As(V) constante para AUD y VS. Conclusión: En los tejidos CV existe asociación As - proteína lo cual podría implicar que el As está unido a biocompuestos de diferente peso molecular a través de grupos sulfhidrilos vecinales. Es probable que el As en AUD y VS se una a fracciones proteicas de masa molecular superior a 80 kDA y a subunidades de la estructura cuaternaria de la proteína nativa.

Background: The effects of arsenic (As) toxi-city - cardiovascular disease, pigmentation, coronary artery occlusion- come from ingestion of contaminated drinking water and environmental exposure. Protein linkage or As(III) and As methylation may be a first step in detoxification. The aim of this study is to evaluate protein linkage of As in the right atrium (RA) and saphenous vein (SV) of As exposed subjects from Antofagasta, Chile Method: As-protein linkage was studied in the cytosol of AD and SV obtained from 6 patients operated on for coronary artery disease. Molecular exclusion columns of 3 different mass ranges were used to obtain the cytosol fraction. As species were detected by induction coupled mass spectrometry and visible ultraviolet spectrometry (links of As and protein thyolates). Results: As was widely distributed in AD and SV in all subjects. As collected in the 3 different columns used were 10 per cent, 25 per cent and 50 per cent. Only As(III) and As(V) were obtained through the method used (IC-HPLC-ICP-MS); a normal distribution was evident for both As species. The relation As(III)/As(V) was similar in AD and SV. Conclusion: A linkage of As and proteins through neighbor sulphidryl groups is present in cardiovascular tissues of exposed subjects. It is likely that As is linked to >80 kDA protein fractions and to quaternary subu-nits or the native protein.

Niveles de elementos traza en tejidos cardiovasculares de pacientes sometidos a cirugía cardíaca en la región de antofagasta: chile / Trace elements in cardiovascular tissues of patients undergoing cardiac surgery in a heavy metal contaminated area, the antofagasta region:chile

Introducción: La población de la Región de Antofagasta se encuentra expuesta a contaminación ambiental por metales pesados (MP). Los elementos traza (ET) podrían actuar con As como agonistas o antagonistas. El presente estudio detalla la determinación de las concentraciones totales (CT) de V, Cr, Mn, Co, Ni, Cu, As, Se y Boro en aurícula derecha (AD), arteria mamaria izquierda (AMI), vena safena (VS) y tejido adiposo (TA) de personas que padecen patologías cardiovasculares (CV) y han requerido cirugía cardíaca. Métodos: Se analizaron AMI, VS, AUD, y TA en un grupo de 50 pacientes con cardiopatía coronaria de la Región de Antofagasta que han sido sometidos a cirugía cardíaca (grupo expuesto, E), y en un grupo de 20 pacientes control sometidos a cirugía cardíaca en el mismo período en Santiago (grupo no expuesto, NE). Las determinaciones de ET y MP se realizaron mediante Técnicas Ópticas y Atómicas. Resultados: En el grupo de pacientes E residentes en la Región de Antofagasta Boro presenta correlaciones interelementales significativas (p=0,05), que no se presentan o son escasas en el grupo NE. El rango de CT de B en AD fue de 24,721 - 932,032 μg/g, niveles muy superiores a los encontrados en el resto de los elementos en estudio. El rango de CT de B encontrada para AD fue de 25,205 - 56,873 μg/g. Conclusión: Individualmente, el elemento más enriquecido en todos los tipos de tejidos del grupo E de la Región de Antofagasta es B, le siguen As y Mn. Cu está empobrecido en el grupo NE, en particular en AD y AMI.

The Antofagasta population is exposed to environmental contamination with heavy metals (HM). Trace elements (TE) might interact with As either as agonists or antagonists. The total concentracions of V, Cr, Mn, Co, Ni, Cu, Se and B in the right atrium (RA), left internal mammary artery (LIMA), saphenous vein (SV) and adipose tissue (AT) from patients undergoing cardiac surgery are reported. Methods: LIMA, SV, RA and AT from 50 patients with myocardial infarction submitted to revascularization surgery in Antofagasta (exposed group, E) or Santiago (non exposed group NE, 20 patients) were analyzed. Optical and atomic techniques were used for analysis of HM and TE. Results: Significant inter elemental correlations were observed for B in group E, (p<0.05), which are not present in group NE. The RA concentrarion of B in group A ranged from 24.72 to 932.03 ug/g, substancially higher than concentracion of the other elements under study. Corresponding concentra-rions of B in the NE group were 25.21 to 56. 87 ug/g. Conclusion: B was the most enriched element in the exposed group, followed by As and Mn. Cu content was significantly lower in RA and LIMA from patients in the non exposed group.