Cistitis hemorrágica tras trasplante alogénico de progenitores hematopoyéticos: experiencia en un centro oncológico pediátrico / Hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: experience in a pediatric oncological institution

Objetivos: Analizar factores de riesgo asociados a la gravedad de lacistitis hemorrágica (CH) y estrategias de tratamiento en pacientes conCH tras trasplante alogénico de progenitores hematopoyéticos (TAPH).Material y métodos: Estudio retrospectivo de historias clínicas. Lospacientes con CH tras TAPH tratados entre 2017 y 2021 se dividieronen dos grupos según la gravedad del cuadro (leve y grave). Se compararon datos demográficos, características específicas de la enfermedad,secuelas urológicas y mortalidad global entre ambos grupos. Se utilizóel protocolo del hospital para el manejo de los pacientes. Resultados: Se recogieron 33 episodios de CH en 27 pacientes, delos cuales el 72,7% fueron varones. La incidencia de CH tras TAPH fuedel 23,4% (33/141). El 51,5% de las CH fueron graves (grados III-IV).La enfermedad de injerto contra huésped (EICH) grave (grados III-IV) yla trombopenia al inicio se asociaron a CH grave (p= 0,043 y p= 0,039,respectivamente). Este grupo tuvo mayor tiempo de hematuria (p<0,001)y necesitó más transfusiones de plaquetas (p= 0,003). Además, el 70,6%precisó sondaje vesical, pero solo un caso cistostomía percutánea. Ningún paciente con CH leve precisó sondaje. No hubo diferencias en lassecuelas urológicas ni en la mortalidad global. Conclusiones: Una CH más grave podría predecirse por la presenciade EICH grave o trombopenia al inicio del cuadro. La CH grave puedemanejarse con sondaje vesical en la mayoría de estos pacientes. Seguirun protocolo estandarizado puede reducir la necesidad de procedimientosinvasivos en pacientes con CH leve.(AU)

Objective: To analyze the risk factors associated with hemorrhagiccystitis (HC) severity and the treatment strategies available in HC patientsfollowing allogeneic hematopoietic stem cell transplantation (AHSCT). Materials and methods: A retrospective study of medical recordswas carried out. Patients with HC following AHSCT treated from 2017to 2021 were divided into two groups according to severity –mild andsevere. Demographic data, disease-specific characteristics, urologicalsequelae, and overall mortality were compared between both groups.The hospital’s protocol was used for patient management. Results: 33 episodes of HC were collected in 27 patients, 72.7% ofwhom were male. HC incidence following AHSCT was 23.4% (33/141).51.5% of HCs were severe (grades III-IV). Severe graft host disease(GHD) (grades III-IV) and thrombopenia at HC onset were associatedwith severe HC (p= 0.043 and p= 0.039, respectively). This group hadlonger hematuria times (p< 0.001) and required more platelet transfusions (p= 0.003). In addition, 70.6% required bladder catheterization,but only 1 case needed percutaneous cystostomy. None of the patientswith mild HC required catheterization. No differences were found interms of urological sequelae or overall mortality. Conclusions: Severe HC could be predicted thanks to the presenceof severe GHD or thrombopenia at HC onset. Severe HC can be managedwith bladder catheterization in most of these patients. A standardizedprotocol may help reduce the need for invasive procedures in patientswith mild HC.(AU)

Enfermedad injerto contra receptor crónica: revisión sistemática de la afectación articular y fascial / Chronic graft-versus-recipient disease: systematic review of joint and fascial involvement

Antecedentes y objetivo: La enfermedad injerto contra receptor crónica (EICRc) es una complicación inmunomediada sistémica que aparece en aproximadamente la mitad de los pacientes sometidos a trasplante alogénico de progenitores hematopoyéticos (alo-TPH) y, aunque se asocia con efectos beneficiosos de injerto versus tumor y tasas de recaída más bajas, sigue siendo la principal causa de morbimortalidad tardía en estos pacientes. El objetivo de esta revisión sistemática de la literatura es proporcionar una visión actual sobre las manifestaciones musculoesqueléticas diagnósticas de EICRc, su evaluación clínica y sus posibilidades terapéuticas. Métodos: Se realizó una búsqueda sistemática en PubMed, Embase y Cochrane Library. Se incluyeron estudios de los últimos 20 años, y se dio prioridad a los estudios transversales para evaluar métodos diagnósticos y a los ensayos clínicos en el caso de artículos referidos a tratamiento. La búsqueda se limitó a humanos y a artículos publicados en inglés o español. Resultados: Identificamos 6423 estudios, de los cuales finalmente seleccionamos 86 (37 sobre clínica y evaluación diagnóstica y 49 sobre tratamientos). Los estudios específicos de complicaciones fasciales y articulares son escasos y de baja calidad, al incluir únicamente casos clínicos aislados o series de casos. La detección temprana de la EICRc con afectación fascial y/o articular requiere de evaluaciones cuidadosas y repetitivas, incluidos exámenes físicos por parte de especialistas con experiencia en trasplantes, comenzando antes del trasplante y continuando a través del seguimiento posterior, para permitir el diagnóstico y la evaluación de la trayectoria de la enfermedad. Conclusiones: Es necesaria la búsqueda de nuevos biomarcadores o de técnicas de imagen avanzada que permitan realizar un diagnóstico precoz. La fisioterapia es esencial para mejorar la funcionalidad y prevenir la progresión de la enfermedad...(AU)

Background and objective: Chronic graft-versus-recipient disease (cGVRD) is a systemic immune-mediated complication that occurs in approximately half of the patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HCT) and, although it is associated with beneficial graft versus tumour effects and lower relapse rates, it remains the leading cause of late morbidity and mortality in these patients. The aim of this systematic review of the literature is to provide a current overview on the diagnostic musculoskeletal manifestations of cGVRD, its clinical evaluation, and therapeutic possibilities. Methods: We ran a systematic search in PubMed, Embase, and Cochrane Library. Studies from the last 20 years were included. Priority was given to cross-sectional studies to evaluate diagnostic methods and to clinical trials in the case of articles referring to treatment. The search was limited to humans and articles published in English or Spanish. Results: We identified 6423 studies, of which we selected 86 (37 on clinical and diagnostic evaluation and 49 on treatments). Specific studies on fascial and joint complications are scarce and of low quality, including only isolated clinical cases or case series. Fasciitis is the most relevant musculoskeletal manifestation, and isolated joint involvement is low, sometimes unnoticed and underdiagnosed, if a thorough exploration of joint mobility is not performed. Early detection of cGVRD with fascial and/or joint involvement requires careful and repeated evaluation. Conclusions: The search for new biomarkers or advanced imaging techniques that allow early diagnosis is necessary. Physiotherapy is essential to improve functionality and prevent disease progression. Controlled studies are needed to establish recommendations on second lines of treatment. Because of its multisystemic nature, cGVRD requires a multidisciplinary approach.(AU)

Chronic graft-versus-recipient disease: Systematic review of joint and fascial involvement.

BACKGROUND AND OBJECTIVE: Chronic graft-versus-host disease (cGVRD) is a systemic immune-mediated complication that occurs in approximately half of the patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HCT) and, although it is associated with beneficial graft versus tumour effects and lower relapse rates, it remains the leading cause of late morbidity and mortality in these patients. The aim of this systematic review of the literature is to provide a current overview on the diagnostic musculoskeletal manifestations of cGVRD, its clinical evaluation, and therapeutic possibilities. METHODS: We ran a systematic search in PubMed, Embase, and Cochrane Library. Studies from the last 20 years were included. Priority was given to cross-sectional studies to evaluate diagnostic methods and to clinical trials in the case of articles referring to treatment. The search was limited to humans and articles published in English or Spanish. RESULTS: We identified 6423 studies, of which we selected 86 (37 on clinical and diagnostic evaluation and 49 on treatments). Specific studies on fascial and joint complications are scarce and of low quality, including only isolated clinical cases or case series. Fasciitis is the most relevant musculoskeletal manifestation, and isolated joint involvement is low, sometimes unnoticed and underdiagnosed, if a thorough exploration of joint motion is not performed. Early detection of cGVRD with fascial and/or joint involvement requires careful and repeated evaluation. CONCLUSIONS: The search for new biomarkers or advanced imaging techniques that allow early diagnosis is necessary. Physiotherapy is essential to improve functionality and prevent disease progression. Controlled studies are needed to establish recommendations on second lines of treatment. Because of its multisystemic nature, cGVRD requires a multidisciplinary approach.

Lisado plaquetario en el tratamiento de la fisura anal crónica y otras indicaciones

Introducción: La aplicación del lisado plaquetario alogénico en el tratamiento de la fisura anal crónica es uno de los temas más novedosos y excitantes dentro de las ciencias biomédicas hoy día. Objetivo: Exponer en forma resumida los avances y perspectivas de empleo del lisado plaquetario alogénico en la fisura anal. Métodos: La estrategia de búsqueda abarcó información en diferentes bases de datos como internet y en el buscador google académico, se utilizaron 42 bibliografías seleccionadas para realizar la revisión, 35 publicadas en los últimos cinco años como artículos originales de revisión, monografías y otros documentos científicos especializados en el tema. A partir de la búsqueda se elaboró el presente artículo. Desarrollo: Se hace alusión a la conceptualización de la enfermedad y los pilares terapéuticos, se sustenta la utilización del lisado plaquetario alogénico; los logros alcanzados con su aplicación en el Hospital General Docente "Comandante Pinaresˮ del municipio San Cristóbal en la provincia Artemisa en la especialidad; así como a las potencialidades de tan promisorio campo en el presente siglo. Conclusiones: El Lisado plaquetario alogénico en el tratamiento de la fisura anal crónica constituyó una nueva modalidad de tratamiento de la enfermedad.

Introduction: The application of allogeneic platelet lysate in the treatment of chronic anal fissure is one of the most novel and exciting topics within biomedical sciences today. Objective: To summarize the advances and perspectives of the use of allogeneic platelet lysate in anal fissure. Methods: The search strategy included information in different databases such as the internet and the academic google search engine, 42 bibliographies selected for the review were used, 35 published in the last five years as original review articles, monographs and other scientific documents specialized in the subject. The present article was prepared on the basis of the search. Development: Allusion is made to the conceptualization of the disease and the therapeutic pillars, the use of allogeneic platelet lysate is sustained; the achievements reached with its application in the General Teaching Hospital "Comandante Pinaresˮ of San Cristóbal municipality in Artemisa province in the specialty; as well as to the potential of such promising field in the present century. Conclusions: Allogeneic platelet lysate in the treatment of chronic anal fissure constituted a new modality of treatment of the disease.

Hipogammaglobulinemia crónica postrasplante de precursores hematopoyéticos y su tratamiento con gammaglobulina subcutánea en pacientes pediátricos / Chronic hypogammaglobulinemia after allogeneic stem cell transplantation and their treatment with subcutanaeos inmunoglobulin in pediatric patients

Introducción: La hipogammaglobulinemia en los primeros meses postrasplante de progenitores hematopoyéticos (TPH) es común en pacientes pediátricos. Durante esta fase se debe administrar tratamiento sustitutivo con inmunoglobulina humana por vía parenteral para la prevención de infecciones. En algunos casos, esta hipogammaglobulinemia persiste en el tiempo, lo que obliga a prolongar el tratamiento cuando el paciente ya no suele ser portador de una vía central, por lo que son candidatos ideales para el tratamiento de reemplazo por vía subcutánea. Existe escasa bibliografía publicada que describa el uso de esta vía en pacientes pediátricos sometidos a TPH; sin embargo, está ampliamente descrita y con muy buenos resultados en el tratamiento de reemplazo en los niños con inmunodeficiencias primarias. Pacientes y métodos: Se realiza un estudio observacional, descriptivo y longitudinal de carácter retrospectivo. Durante los años 2008-2019 se evalúan a todos los pacientes pediátricos sometidos a TPH en nuestro centro que presentan una hipogammaglobulinemia crónica persistente (superior a un año). Se evalúa la fase de tratamiento con inmunoglobulina intravenosa (Privigen®) y los primeros 4 años de tratamiento con inmunoglobulina subcutánea (Hizentra®) mediante un cuestionario. Resultados: Durante los años 2008-2019 se han realizado en nuestro centro 175 trasplantes de precursores hematopoyéticos, de los cuáles 143 (82%) superaron los 3 meses postrasplante. De estos, 3 (2%) pacientes presentaron una hipogammaglobulinemia persistente. Los 3 comparten factores descritos en la bibliografía involucrados en la reconstitución inmune. Mediante el cuestionario se observa que el cambio de gammaglobulina intravenosa a subcutánea ha supuesto una gran mejoría en la calidad de vida de los pacientes. (AU)

Introduction: Hypogammaglobulinemia in the first months after allogeneic hematopoietic stem cell transplantation (HSCT) is common in pediatric patients. During this phase, replacement therapy with human immunoglobulin must be administered parenterally to prevent infections. In some cases, this hypogammaglobulinemia persists over time, which forces further treatment when the patient is usually no longer a carrier of a central line, making them ideal candidates for subcutaneous replacement therapy. There is little published literature describing the use of this method in pediatric patients undergoing HSCT, widely described in replacement treatment in children with primary immunodeficiencies with very good results. Patients and methods: An observational, descriptive, longitudinal and retrospective study is carried out. During the years 2008–2019, we evaluated all pediatric patients undergoing HSCT in our center with persistent chronic hypogammaglobulinemia (for over a year). The treatment phase with intravenous immunoglobulin (Privigen®) and the first four years of treatment with subcutaneous immunoglobulin (Hizentra®) are evaluated using a questionnaire. Results: During the years 2008-2019, 175 patients underwent HSCT, 143 (82%) of whom exceeded three months after transplantation. 3 (2%) of them had persistent hypogammaglobulinemia. All three share factors described in the literature involved in immune reconstitution. After analyzing the questionnaire, it is observed that switching from intravenous to subcutaneous gammaglobulin has involved a great improvement in their quality of life. (AU)

Chronic hypogammaglobulinemia after allogeneic stem cell transplantation and their treatment with subcutaneous immunoglobulin in pediatric patients.

INTRODUCTION: Hypogammaglobulinemia in the first months after allogeneic hematopoietic stem cell transplantation (HSCT) is common in paediatric patients. During this phase, replacement therapy with human immunoglobulin must be administered parenterally to prevent infections. In some cases, this hypogammaglobulinemia persists over time, which forces further treatment when the patient is usually no longer a carrier of a central line, making them ideal candidates for subcutaneous replacement therapy. There is little published literature describing the use of this method in paediatric patients undergoing HSCT, widely described in replacement treatment in children with primary immunodeficiencies with very good results. PATIENTS AND METHODS: An observational, descriptive, longitudinal and retrospective study is carried out. During the years 2008-2019, we evaluated all paediatric patients undergoing HSCT in our center with persistent chronic hypogammaglobulinemia (for over a year). The treatment phase with intravenous immunoglobulin (Privigen®) and the first four years of treatment with subcutaneous immunoglobulin (Hizentra®) are evaluated using a questionnaire. RESULTS: During the years 2008-2019, 175 patients underwent HSCT, 143 (82%) of whom exceeded three months after transplantation. Three (2%) of them had persistent hypogammaglobulinemia. All three share factors described in the literature involved in immune reconstitution. After analysing the questionnaire, it is observed that switching from intravenous to subcutaneous gammaglobulin has involved a great improvement in their quality of life. CONCLUSIONS: The origin of chronic hypogammaglobulinemia in our patients shows different factors and cannot be attributed to a single cause. Due to the limited number of patients no conclusions can be drawn at the population level. We have been able to observe that replacement treatment with Hizentra 20% has been as effective as the intravenous administration without evidence of an increase in bacterial infections. Furthermore, it has also led to an improvement in quality of life and increased comfort, as the patients themselves have stated.

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant / Impacto de las puntaciones del riesgo en los resultados de los pacientes con neoplasias mieloides tras el trasplante alogénico de células madre

Background:The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity.Methods:Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed.Results:175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32–17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%–44%), 28% (21%–35%), 38% (30%–46%) and 24% (17%–31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0–1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0–1 and HCT-CI 0–2 showed OS probabilities of 45% vs. 26% for those with DRI 0–1 and HCT-CI ≥3; p=0.041.Conclusions:In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS. (AU)

Antecedentes:Las principales causas de fallo del trasplante alogénico de células madre hematopoyéticas (alotrasplante) en pacientes con leucemia mieloide aguda (LMA) y síndromes mielodisplásicos (SMD) son las recaídas y la mortalidad debida al trasplante. Se han diseñado diferentes puntuaciones para predecir el pronóstico de dichos pacientes. El objetivo de este estudio fue evaluar qué puntuación o combinación tiene la mejor capacidad predictiva del resultado.Métodos:Análisis retrospectivo de pacientes con LMA y SMD que recibieron un primer alotrasplante de sangre periférica en un único centro, entre diciembre de 2001 y octubre de 2019. Se calcularon las puntuaciones del Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), del European Group for Blood and Marrow Transplantation (EBMT) y del Disease Risk Index (DRI). Para cada puntuación y para las combinaciones HCT-CI/DRI y HCT-CI/EBMT se analizaron la supervivencia global (SG), la incidencia acumulada de recaídas (CIR), la mortalidad no relativa a las recaídas (NRM) y la supervivencia libre de recaídas y libre de enfermedad de injerto versus huésped (GRFS).Resultados:Se evaluaron 175 pacientes. Con un seguimiento medio (rango) de 3,96 (0,32-17,22) años, las probabilidades a 5años (IC95%) de SG, CIR, NRM y GRFS fueron del 36% (28-44), del 28% (21-35), del 38% (30-46) y del 24% (17-31), respectivamente. Para la SG, solo la puntuación DRI seleccionó dos grupos con diferencias estadísticamente significativas (DRI 0-1: 41% vs. DRI≥2: 24%; p=0,011). La combinación de DRI 0-1 y HCT-CI 0-2 reflejó probabilidades de SG del 45% vs. 26% para los pacientes con DRI 0-1 y HCT-CI≥3 (p=0,041).Conclusiones:En los pacientes con LMA y SMD sometidos a alotrasplante la combinación de las puntuaciones HCT-CI y DRI proporcionó la mejor estratificación para la SG. (AU)

Trasplante alogénico en leucemia mieloide aguda y la importancia genética en desarrollo de nuevos tratamientos / Allological transplant in acute myeloid leukemia, the genetic importance for the development of new treatments

La Leucemia Mieloide Aguda es una enfermedad caracterizada por la alteración en la producción de células madre hematopoyéticas y la proliferación celular. Es más común en adultos; a pesar de ello solo se presenta en el 1 % en los Estados Unidos. Entre los 65-68 años se observa una mayor incidencia existiendo de 2-3 casos por cada año en 100.000 habitantes, siendo aproximadamente el 10 % de los cánceres de este tipo. Los diagnósticos más recomendados para esta enfermedad son los de carácter sanguíneo, la realización de citometrías de flujo en muestra de médula ósea. Según estudios, los análisis citogenéticos en un gran número de pacientes han demostrado translocaciones e inversiones en los cromosomas somáticos, mientras que solo una minoría tiene una organización de cromosomas somáticos balanceada. La terapia de consolidación se acompaña del trasplante de células madre hematopoyéticas, conocido como el trasplante alogénico, que puede ser potencialmente curativo en algunos pacientes.

The acute myeloid leukemia, is a disease which is a characterized by an irregular production of hematopoietic cells and cellular proliferation. It´s most common in adults, however only 1% of American adults will be diagnosed throughout their lives. Between the ages of 65-68 there is a high incidence with only 2-3 cases per 100.000 patients; making up only 10% of this type of cancer. It´s mainly diagnosed by using blood test, flow cytometry (on Bone Marrow samples). Some cytogenetic studies suggest that in a significant number of patients both somatic chromosomal inversion and translocation are present, while only a small percentage show no somatic chromosomal mutations. Consolidation therapy with a hematopoietic Stem Cells transplant, also known as a "allogenic transplant", can be potentially curative in some special cases.

Transplantation of hematopoietic progenitors in myelofibrosis.

The objective of this work is to generate recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles published between 1999 and 2015 (January) was used as a source of scientific evidence. The recommendations were produced through a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and the European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention, and management of post-transplant relapse. Patients with intermediate-2 or high-risk disease and age < 70 years should be considered candidates for allo-SCT. Patients with intermediate-risk 1 disease and age < 65 years should be considered candidates if they have refractory transfusion-dependent anemia, or a peripheral blood (PB) blast percentage > 2%, or adverse cytogenetics. Splenectomy before transplantation must be decided on a case-by-case basis. Patients with intermediate-2 or high-risk disease who lack a human leukocyte antigen (HLA)-matched sibling or unrelated donor should be enrolled in a protocol that uses HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for transplants from HLA-matched unrelated donors and siblings. The optimal intensity of the conditioning regimen has yet to be defined. Strategies such as discontinuation of immunosuppressive drugs, infusion of donor lymphocytes, or both were considered adequate to prevent clinical relapse. In conclusion, we provide consensus-based recommendations aimed at optimizing allo-SCT in PMF. Unmet clinical needs were highlighted.

El objetivo de este trabajo es generar recomendaciones sobre el manejo del trasplante alogénico de células madre (alo-SCT) en la mielofibrosis primaria (MFP). Se utilizó una revisión sistemática integral de artículos publicados entre 1999 y 2015 (enero) como fuente de evidencia científica. Las recomendaciones se produjeron mediante un proceso Delphi en el que participó un panel de 23 expertos designados por la European LeukemiaNet y el European Blood and Marrow Transplantation Group. Las preguntas clave incluyeron la selección de pacientes, la selección de donantes, el manejo previo al trasplante, el régimen de acondicionamiento, el manejo posterior al trasplante, la prevención y el manejo de la recaída después del trasplante. Los pacientes con enfermedad de riesgo intermedio 2 o alto y edad < 70 años deben ser considerados candidatos para alo-SCT. Los pacientes con enfermedad de riesgo intermedio 1 y edad < 65 años deben ser considerados candidatos si presentan anemia refractaria dependiente de transfusiones, o un porcentaje de blastos en sangre periférica > 2%, o citogenética adversa. La esplenectomía previa al trasplante debe decidirse caso por caso. Los pacientes con enfermedad de riesgo intermedio 2 o alto que carecen de un hermano compatible con el antígeno leucocitario humano (HLA) o de un donante no emparentado deben inscribirse en un protocolo que utilice donantes no idénticos de HLA. PB se consideró la fuente más apropiada de células madre hematopoyéticas para trasplantes de hermanos y donantes no emparentados compatibles con HLA. La intensidad óptima del régimen de acondicionamiento aún debe definirse. Se consideraron adecuadas estrategias como la suspensión de los fármacos inmunosupresores, la infusión de linfocitos del donante o ambas para evitar la recaída clínica. En conclusión, proporcionamos recomendaciones basadas en consenso destinadas a optimizar el alo-SCT en MFP. Se destacaron las necesidades clínicas insatisfechas.

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant.

BACKGROUND: The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity. METHODS: Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed. RESULTS: 175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32-17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%-44%), 28% (21%-35%), 38% (30%-46%) and 24% (17%-31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0-1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0-1 and HCT-CI 0-2 showed OS probabilities of 45% vs. 26% for those with DRI 0-1 and HCT-CI ≥3; p=0.041. CONCLUSIONS: In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS.

Resultados del trasplante de progenitores hematopoyéticos de donante no emparentado con o sin globulina antitimocítica como profilaxis de la enfermedad del injerto contra receptor en pacientes con leucemia aguda y síndrome mielodisplásico / Outcomes of unrelated donor stem cell transplantation with or without anti-thymocyte globulin used as graft-versus-host disease prophylaxis in patients with acute leukaemia and myelodysplastic syndrome

Fundamento y objetivo: La enfermedad del injerto contra el receptor (EICR) y las infecciones son complicaciones del trasplante alogénico de progenitores hematopoyéticos (alo-TPH). La globulina antitimocítica (ATG) es una estrategia empleada para la profilaxis de la EICR. Este estudio analiza los resultados y la frecuencia de infecciones en función del uso de ATG, después de un alo-TPH de donante no emparentado (DNE) en pacientes con leucemia aguda y síndrome mielodisplásico.Pacientes y métodoEstudio retrospectivo de pacientes que recibieron un alo-TPH de DNE entre diciembre de 2007 y abril de 2019. Se compararon los principales resultados en función del uso de ATG.ResultadosSe incluyó a 66 pacientes. No se encontraron diferencias significativas en el grupo ATG (n=50) frente al no ATG (n=16) en supervivencia global, incidencia acumulada de recaída, mortalidad no debida a recaída o incidencia acumulada de EICR aguda o crónica. Hubo mayor frecuencia de infecciones en el grupo ATG (60 frente a 19%; p=0,004).ConclusionesEn este estudio no se demostró diferencia en los principales resultados del alo-TPH en función del uso de ATG, pero hubo más infecciones en el grupo que recibió ATG. (AU)

Background and purpose: Graft-versus-host disease (GVHD) and infections are complications after allogeneic stem cell transplantation (alloSCT). Anti-thymocyte globulin (ATG) is a strategy used as prophylaxis for GVHD. The study analyses the outcomes and frequency of infections with or without ATG after an unrelated donor alloSCT in patients with acute leukaemia and myelodysplastic syndrome.Patients and methodsRetrospective study of patients receiving an unrelated donor alloSCT between December 2007 and April 2019. The main outcomes were analysed according to use or not of ATG.ResultsSixty-six patients were included. No significant differences were found between the ATG group (n=50) vs. no-ATG group (n=16) in overall survival, cumulative incidence of relapse, cumulative incidence of non-relapse mortality or cumulative incidence of acute GVHD or chronic GVHD. There was a greater frequency of infections in the ATG group (60 vs. 19%, P=.004).ConclusionsIn this study, no differences were shown in the main outcomes of alloSCT based on the use of ATG, although more infections were documented in the ATG group. (AU)

Estudio prospectivo del seguimiento de pacientes largos supervivientes a un trasplante alogénico de progenitores hematopoyéticos / Prospective follow-up of adult long-term survivors of allogeneic haematopoietic stem cell transplantation

Fundamento y objetivo: Los pacientes que sobreviven más allá de 2 años del trasplante de progenitores hematopoyéticos (TPH), tienen un riesgo aumentado de complicaciones a largo plazo, que tienen impacto en su supervivencia y calidad de vida. El objetivo de este estudio fue diseñar y aplicar un protocolo de seguimiento a largo plazo para detectar necesidades no cubiertas y tratar precozmente dichas complicaciones.Pacientes y métodoA los supervivientes más allá de 2 años del TPH alogénico (aloTPH) se aplicó una sistemática de estudio para detectar y tratar complicaciones y problemas a largo plazo dentro de una unidad funcional interdisciplinar.ResultadosTreinta y seis (36%) de los 99 pacientes incluidos, requirieron de intervención en alguno de los factores de riesgo cardiovascular mediante educación sanitaria o administración de fármacos antihipertensivos e hipolipemiantes. Nueve (25%) de 36 pacientes requirieron aporte de calcio y vitamina D. Se detectó una baja reincorporación de las mujeres a los protocolos de detección de neoplasias ginecológicas, y una baja adherencia al seguimiento odontológico tras el aloTPH.ConclusiónEl seguimiento de los largos supervivientes a un aloTPH en una unidad multidisciplinaria permitió detectar necesidades no cubiertas, que afectaron especialmente al riego cardiovascular, metabolismo óseo, prevención del cáncer y control odontológico. (AU)

Background and objective: Patients who survive beyond two years after haematopoietic stem cell transplantation (HSCT) have an increased risk of long-term complications, which impact on their survival and quality of life. The aim of this study was to design and apply a long-term follow-up protocol to detect unmet needs and treat these complications early.Patients and methodA prospective study to detect and treat complications and long-term problems within an interdisciplinary functional unit was applied to survivors beyond 2 years of allogeneic HSCT (alloHSCT).ResultsThirty-six (36%) of the 99 patients included, required intervention in a cardiovascular risk factor by health education or antihypertensive and lipid-lowering drugs. Nine of 36 (25%) patients required calcium and vitamin D intake. Low inclusion of women in gynaecological neoplasm detection protocols was detected, as well as a low adherence to dental follow-up after alloHSCT.ConclusionThe follow-up of long-term survivors after alloHSCT in a multidisciplinary unit allowed unmet needs to be detected and controlled, especially in cardiovascular risk, bone metabolism, cancer prevention, and dental control. (AU)

Prospective follow-up of adult long-term survivors of allogeneic haematopoietic stem cell transplantation. / Estudio prospectivo del seguimiento de pacientes largos supervivientes a un trasplante alogénico de progenitores hematopoyéticos.

BACKGROUND AND OBJECTIVE: Patients who survive beyond two years after haematopoietic stem cell transplantation (HSCT) have an increased risk of long-term complications, which impact on their survival and quality of life. The aim of this study was to design and apply a long-term follow-up protocol to detect unmet needs and treat these complications early. PATIENTS AND METHOD: A prospective study to detect and treat complications and long-term problems within an interdisciplinary functional unit was applied to survivors beyond 2 years of allogeneic HSCT (alloHSCT). RESULTS: Thirty-six (36%) of the 99 patients included, required intervention in a cardiovascular risk factor by health education or antihypertensive and lipid-lowering drugs. Nine of 36 (25%) patients required calcium and vitamin D intake. Low inclusion of women in gynaecological neoplasm detection protocols was detected, as well as a low adherence to dental follow-up after alloHSCT. CONCLUSION: The follow-up of long-term survivors after alloHSCT in a multidisciplinary unit allowed unmet needs to be detected and controlled, especially in cardiovascular risk, bone metabolism, cancer prevention, and dental control.

Outcomes of unrelated donor stem cell transplantation with or without anti-thymocyte globulin used as graft-versus-host disease prophylaxis in patients with acute leukaemia and myelodysplastic syndrome. / Resultados del trasplante de progenitores hematopoyéticos de donante no emparentado con o sin globulina antitimocítica como profilaxis de la enfermedad del injerto contra receptor en pacientes con leucemia aguda y síndrome mielodisplásico.

BACKGROUND AND PURPOSE: Graft-versus-host disease (GVHD) and infections are complications after allogeneic stem cell transplantation (alloSCT). Anti-thymocyte globulin (ATG) is a strategy used as prophylaxis for GVHD. The study analyses the outcomes and frequency of infections with or without ATG after an unrelated donor alloSCT in patients with acute leukaemia and myelodysplastic syndrome. PATIENTS AND METHODS: Retrospective study of patients receiving an unrelated donor alloSCT between December 2007 and April 2019. The main outcomes were analysed according to use or not of ATG. RESULTS: Sixty-six patients were included. No significant differences were found between the ATG group (n=50) vs. no-ATG group (n=16) in overall survival, cumulative incidence of relapse, cumulative incidence of non-relapse mortality or cumulative incidence of acute GVHD or chronic GVHD. There was a greater frequency of infections in the ATG group (60 vs. 19%, P=.004). CONCLUSIONS: In this study, no differences were shown in the main outcomes of alloSCT based on the use of ATG, although more infections were documented in the ATG group.

Comparison of matched sibling, unrelated and haploidentical donors in hematopoietic stem cell transplantation. A real world experience from the Argentine Group For Bone Marrow Transplantation And Cell Therapy (GATMO-TC) / Comparación de donantes relacionados, no relacionados y haploidénticos en trasplante de progenitores hematopoyéticos. Experiencia del Grupo Argentino de Trasplante de Médula Ósea y Terapia Celular (GATMO-TC)

Abstract We retrospectively analyzed 570 adult patients who received allogeneic stem cell transplantation for malignant diseases. The outcomes were compared according to donor type. Most of the patients (60%) were transplanted for acute leukemia. Median follow-up was 1.6 years. Haploidentical allogeneic stem cell transplantation was more frequently performed for acute myeloid leukemia and in late stages than any other donor type. Non-relapse mortality at 100 days and one year for unrelated and haploidentical donors were similar, 19%-29% vs. 17%-28%, respectively. A significant better non-relapse mortality was observed for matched sibling donors (7%-15%; p < 0.001). Relapse rate was higher in haploidentical donors compared to matched sibling and unrelated donors (three year relapse rate 46%, 39%, 28%; respectively p < 0.001). Haploidentical donors resulted in lower three year progression-free survival and worse 3 year overall survival (32%; p < 0.001 and 42%; p < 0.001) compared with other donors (44% and 55% MSD, 40% and 42% UD, respectively). The incidence of grade II-IV acute graft-versus-host disease was higher in unrelated donors (51% unrelated, 35% haploidentical, 36% matched sibling; respectively; p = 0.001), with no difference in grades III-IV (p = 0.73) or in chronic graft-versus-host disease (p = 0.2) between groups. After multivariate analysis, haploidentical and unrelated donors remained negatively associated with non-relapse mortality (HR 1.95; 95% CI 1.10-3.20 and HR 2.70; 95% CI 1.63-4.46, respectively). Haploidentical donors were associated with a higher risk of relapse and worse overall survival. This analysis shows that haploidentical donors were associated with similar non-relpase mortality and higher relapse rates than unrelated donors. Better results in non-relapse mortality were observed for matched sibling donors.

Resumen Se efectuó un análisis retrospectivo de 570 pacientes adultos que recibieron un trasplante alogénico de precursores hematopoyéticos, comparando los resultados según el tipo de donante. La mediana de seguimiento fue de 1.6 años. El 60% de la población se trasplantó por leucemias agudas. Los trasplantes haploidénticos se hicieron en su mayoría en leucemia mieloide aguda y en estadios tardíos en comparación a otros donantes. La mortalidad libre de enfermedad al día +100 y a 1 año fue similar para los donantes no emparentados y haploidénticos (19% y 29% vs. 17% y 28%, respectivamente). Se obtuvieron mejores resultados con donantes relacionados idénticos (7% y 15%; p < 0.001). La recaída fue mayor en los donantes haploidénticos (tres años 46% haploidénticos, 39% relacionados idénticos, 28% no emparentados; p < 0.003). El trasplante con donante haploidéntico presentó una menor supervivencia libre de progresión y menor supervivencia global a tres años (32%; p < 0.001 y 42%; p < 0.001). La incidencia de enfermedad injerto contra huésped aguda fue mayor en no emparentados (51%, 35% haploidénticos, 36% relacionados idénticos; p = 0.001), sin diferencias en grados III-IV (p = 0.73) o en EICH crónica (p = 0.2). Los trasplantes con donante haploidéntico y no emparentado mantuvieron su asociación negativa con mortalidad libre de enfermedad (HR 1.95; 95%IC 1.10-3.20 y HR 2.70; 95%IC 1.63-4.46), en análisis multivariado. El trasplante haploidéntico se asoció a mayor recaída y a menor supervivencia global. Esta experiencia mostró similar mortalidad libre de enfermedad entre trasplantes con donantes haploidénticos y no emparentados. Los trasplantes relacionados idénticos mostraron menores tasas de mortalidad libre de enfermedad.

Trasplante facial generalidades / Facial trasplant generalities

Resumen El trasplante facial es un alotrasplante compuesto vascularizado que busca la reconstrucción de defectos masivos faciales permitiendo la reinserción social del receptor, generando un impacto positivo sobre su calidad de vida. El objetivo de este artículo fue realizar una revisión de la literatura sobre generalidades del trasplante facial, enfocándose en los cuidados pre, intra y postoperatorios concernientes a la temática. La búsqueda bibliográfica se realizó desde el 13 de septiembre del 2018 hasta el 31 de marzo del 2019 utilizando los términos MESH "Face Transplant" y "Face Transplantation". Aplicando los criterios de inclusión y exclusión se obtuvieron 43 artículos sobre los cuales se desarrolló la revisión. El trasplante facial es un procedimiento nuevo en el cual hay muchas áreas por explorar, sin embargo, es una alternativa prometedora a los métodos utilizados para la reconstrucción de lesiones faciales complejas, que se optimizará a medida que se extienda su uso. MÉD.UIS.2020;33(3): 29-36

Abstract The facial transplant is a vascularized compound allogeneic transplant that seeks the reconstruction of massive facial defects allowing the social reintegration of the recipient, generating a positive impact on their quality of life. The objective of this article was to review the literature on generalities of facial transplantation, focusing on the pre, intra and postoperative care regarding the subject. The bibliographic search was performed from September 13, 2018 to March 31, 2019 using the MESH terms "Face Transplant" and "Face Transplantation". Applying the inclusion and exclusion criteria, 43 articles were obtained on which the review was developed. Facial transplantation is a new procedure in which there are many areas to explore, however, it is a promising alternative to the methods used for the reconstruction of complex facial injuries, which will be optimized as its use expands. MÉD.UIS.2020;33(3): 29-36

Manifestaciones cutáneas de la enfermedad injerto versushuésped en una población pediátrica y de adultos jóvenes / Cutaneous manifestations of graft versus host disease in a population of pediatric and young adults patients

El trasplante de médula ósea es una terapia potencialmente curativa para múltiples enfermedades; el alogénico es el más indicado en leucemias. La enfermedad injerto versus huésped (EIVH) constituye la principal complicación del trasplante de médula ósea alogénico. Tanto en la EIVH aguda como crónica, la piel es el órgano más frecuentemente comprometido. El objetivo fue analizar las manifestaciones cutáneas de esta entidad. Trabajo retrospectivo y descriptivo, que incluyó a 59 pacientes trasplantados de edades entre 0 y 20 años. En 50 casos, se realizó trasplante de médula ósea alogénico. Veinticinco pacientes desarrollaron EIVH (17, la forma aguda, y 8, la forma crónica), y 24 tuvieron compromiso cutáneo. En concordancia con lo comunicado se encontró que las manifestaciones cutáneas fueron la manifestación clínica más común de EIVH. El hallazgo principal en EIVH aguda en nuestra serie fue el rash eritematoso maculopapular y, en EIVH crónica, las lesiones escleróticas símil morf

Bone marrow transplant is a potentially curative therapy for several diseases, and allogeneic bone marrow transplant is the most commonly indicated type for leukemias. Graft versus host disease (GVHD) is the main complication of allogeneic bone marrow transplant. In both acute and chronic GVHD, the skin is the most frequently involved organ. The objective of this study was to analyze cutaneous manifestations of this disease. Retrospective and descriptive study that included 59 transplanted patients aged 0 to 20 years. In 50 cases allogeneic bone marrow transplant was performed. Twenty-five patients developed GVHD (17 acute disease and 8 chronic disease) and 24 of them had cutaneous involvement. According to the literature, skin compromise was the commonest clinical manifestation of GVHD. Main finding in acute GVHD in our series was the erythematous maculopapular rash, while in chronic GVHD they were sclerotic lesions resembling morphe

Trasplante de progenitores hematopoyéticos alogénico haploidéntico en aplasia medular, reporte del primer caso en Cuba / Allogenic hematopoietic stem-cell transplantation in marrow aplasia: the first case report in cuba

Introducción: La aplasia medular adquirida grave es una enfermedad hematológica infrecuente caracterizada por una disminución o ausencia de precursores hematopoyéticos en la médula ósea, lo cual se expresa con distintos grados de citopenias. Varios factores, infecciosos o no, pueden incidir en su origen. Su manejo es complejo y puede incluir tratamiento inmunosupresor y trasplante de progenitores hematopoyéticos alogénico. Objetivo: Demostrar la utilidad de la realización del trasplante de progenitores hematopoyéticos alogénico haploidéntico en pacientes con aplasia medular grave. Caso clínico: Paciente masculino de 21 años de edad, con antecedentes de salud, que en octubre del 2018 debutó con íctero, pancitopenia, lesiones purpúrico hemorrágicas en piel y mucosas, en el curso de una hepatitis aguda seronegativa. La biopsia de médula ósea mostró aplasia medular severa. Se inició tratamiento inmunosupresor con globulina antitimocίtica, ciclosporina A y metilprednisolona. Al cabo de los 6 meses mantenía trombocitopenia severa con necesidades transfusionales y en octubre de 2019 se decide realizar trasplante de progenitores hematopoyéticos alogénico con donante haploidéntico y empleando como tratamiento acondicionante globulina antitimocίtica, fludarabina, ciclofosfamida y bajas dosis de irradiación corporal total. En evaluación clίnica de julio de 2020 (dίa + 280 del trasplante) el paciente estaba asintomático y con parámetros hematológicos normales. Conclusiones: Se demostró que el trasplante de progenitores hematopoyéticos alogénico haploidéntico es un proceder realizable y útil en pacientes con aplasia medular grave, lo cual corrobora el beneficio clínico que puede aportar su ejecución en pacientes con esta enfermedad(AU)

Introduction: Acquired severe marrow aplasia is a rare hematological disease characterized by decrease or absence of hematopoietic precursors in bone marrow, which is expressed with different degrees of cytopenias. Several factors, infectious or not, can influence its origin. Its management is complex and may include immunosuppressive treatment and allogeneic hematopoietic stem-cell transplantation. Objective: To demonstrate the usefulness of performing haploidentical allogeneic hematopoietic stem-cell transplantation in patients with severe medullary aplasia. Clinical case: A 21-year-old male patient, with medical history, who first presented, in October 2018, with icterus, pancytopenia, as well as purpuric hemorrhagic lesions on the skin and mucosa, in the course of acute seronegative hepatitis. The bone marrow biopsy showed severe marrow aplasia. Immunosuppressive treatment was started with antithymocytic globulin, cyclosporine A, and methylprednisolone. After six months, he maintained severe thrombocytopenia under transfusion requirements and, in October 2019, the decision was to perform allogeneic hematopoietic stem-cell transplantation with a haploidentical donor and using antithymocyte globulin, fludarabine, cyclophosphamide, and low doses of total body irradiation as conditioning treatment. In the clinical assessment carried out in July 2020 (day +280 after transplantation), the patient was asymptomatic and with normal hematological parameters. Conclusions: Transplantation of haploidentic allogeneic hematopoietic progenitors was shown to be a feasible and useful procedure in patients with severe marrow aplasia, which corroborates the clinical benefit that its execution can bring in patients with this disease(AU)

Study of cytomegalovirus resistance in allogeneic hematopoietic cell transplant recipients. / Estudio de resistencias de citomegalovirus en pacientes receptores de trasplante alogénico de progenitores hematopoyéticos.

INTRODUCTION: Cytomegalovirus (CMV) is the most important opportunistic pathogen associated with transplant. The objective of this study was the characterization of CMV resistance mutations in allogeneic haematopoietic cell transplant recipients (allo-TPH) and the study of associated factors. METHODS: A retrospective study of a cohort of allo-TPH recipients with post-transplant CMV reactivations with stable or increasing viral loads (CV), despite adequate antiviral treatment for at least 2weeks. The study of resistance mutations of the UL97 and UL54 genes was carried out by Sanger sequencing. RESULTS: Refractory CMV infection in our group of allo-TPH patients corresponded with a 21.43% rate of resistant virus infection (3 of 14 patients). All patients with resistance mutations had multiple reactivation episodes (P-value .01). The mutations found were A594V and H520Q in the UL97 gene that confers high-grade resistance to ganciclovir (GCV). One of the 3 cases with antiviral resistance was documented with a low VL (< 1000 copies/ml) and short accumulated GCV treatment (41 days). CONCLUSION: Most of the failures in the treatment of CMV were possibly due to clinical resistance; the lack of satisfactory response to antiviral treatment is not always accompanied by virological resistance. However, the appearance of resistances can occur early after the start of the treatment and with VL below 1000 copies / ml. The number of episodes of reactivation was higher among patients with virological resistance than those who did not.

Allogeneic stem cell transplantation in the era of novel therapies for acute lymphoblastic leukaemia. / El trasplante alogénico de progenitores hematopoyéticos en la era de las nuevas terapias en la leucemia linfoblástica aguda.

Immunotherapy is changing the treatment of acute lymphoblastic leukaemia (ALL) in adults and children. However, regardless of these new therapies, allogeneic hematopoietic cell transplantation (allo-HCT) still play a key role in the treatment of ALL, although it is uncertain how these new therapies will impact on the transplant procedure and indications. This article reviews the indications of allo-HCT for children and adults diagnosed with ALL, the different sources and conditioning regimens for transplantation as well as the role of measurable residual diseases pre- and post-HCT in the era of the new therapies for ALL.