Common mental disorders in hematopoietic stem cell transplant patients: a scoping review / Trastornos mentales comunes en pacientes con trasplante de células madre hematopoyéticas: revisión del alcance / Transtornos mentais comuns em pacientes transplantados com células-tronco hematopoéticas: revisão de escopo

ABSTRACT Objective: to map common recurrent mental disorders in patients undergoing hematopoietic stem cell transplantation. Methods: this is a scoping review carried out in January 2022 in electronic databases and repositories of dissertations and thesis. Studies that answered the research question, met the objective of the study and were available in full electronically, in any language, were included. Results: the sample consisted of 28 studies, 14 of which were published in the United States of America. The common mental disorders found were depressive, anxiety, post-traumatic stress and mood disorders. Twenty symptoms were mentioned, among the most prevalent are fatigue and sleep disorders/insomnia. Conclusions: the difficulty and importance of carrying out the differential diagnosis of these disorders were highlighted, since their symptoms can be confused with other health problems and have a strong potential to interfere with patients' evolution.

RESUMEN Objetivo: mapear los trastornos mentales recurrentes comunes en pacientes sometidos a trasplante de células madre hematopoyéticas. Métodos: se trata de una revisión de alcance realizada en enero de 2022 en bases de datos electrónicas y repositorios de disertaciones y tesis. Se incluyeron publicaciones que respondieron a la pregunta de investigación, cumplieron con el objetivo del estudio y estaban disponibles en su totalidad en formato electrónico, en cualquier idioma. Resultados: la muestra estuvo compuesta por 28 estudios, 14 de los cuales fueron publicados en los Estados Unidos de América. Los trastornos mentales comunes encontrados fueron depresión, ansiedad, estrés postraumático y trastornos del estado de ánimo. Se mencionaron 20 síntomas, entre los más prevalentes se encuentran fatiga y trastornos del sueño/insomnio. Conclusiones: se destacó la dificultad e importancia de realizar el diagnóstico diferencial de estos trastornos, ya que sus síntomas pueden confundirse con otros problemas de salud y tienen un fuerte potencial de interferir en la evolución del paciente.

RESUMO Objetivo: mapear os transtornos mentais comuns recorrentes em pacientes submetidos ao transplante de células-tronco hematopoéticas. Métodos: trata-se de revisão de escopo realizada em janeiro de 2022 em bases de dados eletrônicas e repositórios de dissertações e tese. Foram incluídas publicações que respondessem à questão de pesquisa, atendessem ao objetivo do estudo e que estivessem disponíveis na íntegra em meio eletrônico, em qualquer idioma. Resultados: a amostra foi composta por 28 estudos, dos quais 14 foram publicados nos Estados Unidos da América. Os transtornos mentais comuns encontrados foram os transtornos depressivos, de ansiedade, estresse pós-traumático e de humor. Foram citados 20 sintomas, entre os mais prevalentes estão a fadiga e distúrbios do sono/insônia. Conclusões: evidenciaram-se a dificuldade e a importância de realizar o diagnóstico diferencial desses transtornos, uma vez que seus sintomas podem ser confundidos com outros problemas de saúde e têm forte potencial para interferir na evolução do paciente.

The impact of multiple myeloma induction therapy on hematopoietic stem cell mobilization and collection: 25-year experience

ABSTRACT While first-line induction therapy for patients with multiple myeloma has changed over the years, autologous hematopoietic stem cell transplantation still plays a significant role, improving both depth of response and progression-free survival of myeloma patients. Our 25-year experience in mobilizing hematopoietic stem and progenitor cells for 472 transplant-eligible myeloma patients was retrospectively reviewed. Patients were stratified according to the remission induction therapy received, and the outcomes were compared among the cohorts that received vincristine, adriamycin and dexamethasone (VAD) (n = 232), bortezomib and dexamethasone (BD) (n = 86), cyclophosphamide, bortezomib and dexamethasone (CyBorD) (n = 82) and other regimens (n = 67). Cyclophosphamide plus granulocyte colony-stimulating factor was the predominant mobilization regimen given. A greater number of CD34+ cells (9.9 × 10E6/kg, p = 0.026) was collected with less hospital admissions in BD patients (13%, p = 0.001), when compared to those receiving VAD (7.5 × 10E6/kg, 29%), CyBorD (7.6 × 10E6/kg, 19%), or other regimens (7.9 × 10E6/kg, 36%). Induction therapy did not influence the overall rate of unscheduled visits or the length of hospitalization because of complications following mobilization. The myeloma response was not significantly deepened following the cyclophosphamide administered for mobilization. This analysis demonstrates the importance of monitoring the impact of initial treatment on downstream procedures such as stem cell mobilization and collection.

The impact of multiple myeloma induction therapy on hematopoietic stem cell mobilization and collection: 25-year experience.

While first-line induction therapy for patients with multiple myeloma has changed over the years, autologous hematopoietic stem cell transplantation still plays a significant role, improving both depth of response and progression-free survival of myeloma patients. Our 25-year experience in mobilizing hematopoietic stem and progenitor cells for 472 transplant-eligible myeloma patients was retrospectively reviewed. Patients were stratified according to the remission induction therapy received, and the outcomes were compared among the cohorts that received vincristine, adriamycin and dexamethasone (VAD) (n=232), bortezomib and dexamethasone (BD) (n=86), cyclophosphamide, bortezomib and dexamethasone (CyBorD) (n=82) and other regimens (n=67). Cyclophosphamide plus granulocyte colony-stimulating factor was the predominant mobilization regimen given. A greater number of CD34+ cells (9.9×10E6/kg, p=0.026) was collected with less hospital admissions in BD patients (13%, p=0.001), when compared to those receiving VAD (7.5×10E6/kg, 29%), CyBorD (7.6×10E6/kg, 19%), or other regimens (7.9×10E6/kg, 36%). Induction therapy did not influence the overall rate of unscheduled visits or the length of hospitalization because of complications following mobilization. The myeloma response was not significantly deepened following the cyclophosphamide administered for mobilization. This analysis demonstrates the importance of monitoring the impact of initial treatment on downstream procedures such as stem cell mobilization and collection.

Revisión literaria sobre el trasplante de células madre hematopoyéticas, opciones para mejorar la asimilación y su impacto en la supervivencia de los pacientes / Literary review on the transplantation of hematopoietic stem cells, options to improve the assimilation and its impact on the survival of patients

El trasplante de células madre hematopoyéticas resulta un procedimiento muy beneficioso para el tratamiento de enfermedades hematológicas en las cuales la única posibilidad de cura es por medio de este método. Para realizar el trasplante existen varias opciones: trasplante autólogo y alogénico. Existen complicaciones que han tratado de evitarse adoptando medidas que en algunas ocasiones han resultado exitosas. El beneficio que este procedimiento representa ha hecho que sea adoptado por muchas personas y ha llevado al aumento de donantes a nivel mundial..(AU)

Hematopoietic stem cells transplantation is a very beneficial procedure for the treatment of hematological diseases in which the only possibility of cure is by this method. There are several options to perform the transplant: autologous and allogeneic transplant.There are complications that have been trying to avoid adopting measures that have sometimes been successful. The benefit that this procedure represents has made it adopted by many people and has led to the increase of donors worldwide..(AU)

Ação educativa para a padronização no manejo do cateter de hickman® / Acción educativa para estandarizar el manejo del catéter de hickman® / Educational action for standardization in the management of hickman catheters®

RESUMO Objetivo: habilitar a equipe de Enfermagem de um serviço de transplante de células-tronco hematopoiéticas no manejo do cateter de Hickman®. Método: pesquisa descritiva e quantitativa. A coleta de dados ocorreu entre janeiro e março de 2017, em um hospital público do Sul do Brasil, por meio de questionários que foram analisados mediante estatística descritiva. Resultados: habilitaram-se 44 participantes. Das questões abordadas, tiveram melhor resultado após as orientações: definição de cateter venoso central de curta permanência (79,55% para 93,18%de acertos); material e posição do cateter (75% para 88,64%); características do cateter (54,55% para 65,91%); procedimentos imediatos à inserção do cateter (2,27% para 18,18%); lavagem, pressão positiva e refluxo induzido pela seringa (72,73% para 97,73%); bloqueio do cateter (84,09% para 97,73%); volume do priming(22,73%para 54,55%) Conclusão: o processo educativo desenvolvido possibilitou a instrumentalização dos profissionais para um conhecimento mais homogêneo no manejo do cateter de Hickman®.

RESUMEN Objetivo: Capacitar al equipo de Enfermería de un servicio de trasplante de células madre hematopoyéticas en el manejo del catéter de Hickman®. Método: Investigación descriptiva, cuantitativa. Datos recolectados entre enero y marzo de 2017 en hospital público delo Sur de Brasil, mediante cuestionarios, que fueron analizados por estadística descriptiva. Resultados: Recibieron capacitación los 44 participantes. Las cuestiones abordadas obtuvieron mejores resultados después de las indicaciones: definición de catéter venoso de corta permanencia (79,55% al 93,18% de aciertos); material y posición del catéter (75% al 88,64%); características del catéter (2,27% al 18,18%); higiene, presión positiva y reflujo inducido por jeringa (72,73% al 97,73%); bloqueo del catéter (84,09% al 97,73%) volumen del priming (22,73% al 54,55%). Conclusión: El proceso educativo desarrollado permitió el desarrollo por parte de los profesionales de un conocimiento más homogéneo en el manejo del catéter de Hickman®.

ABSTRACT Objective: to enable the nursing team of a hematopoietic stem cell transplantation service to manage Hickman® catheters. Method: descriptive and quantitative research. Data collection took place between January and March 2017, in a public hospital in the South of Brazil, using questionnaires that were analyzed through descriptive statistics. Results: Forty-four participants were enrolled. Of the issues addressed, the ones with better results after the guidelines were: definition of a short-term central venous catheter (79.55% for 93.18% of correct answers); material and position of the catheter (75% to 88.64%); characteristics of the catheter (54.55% to 65.91%); immediate procedures after catheter insertion (2.27% to 18.18%); flushing, positive pressure and syringe-induced reflux (72.73% to 97.73%); catheter lock (84.09% to 97.73%); and priming volume (22.73% to 54.55%). Conclusion: the educational process developed allowed the instrumentalization of professionals to a more homogenous knowledge in the management of Hickman® catheters.

Sugestões de orientações para alta de crianças no pós-transplante de células-tronco hematopoiéticas* / Suggestions for the improvement of guidance at the hospital discharge of children in post hematopoietic stem cell transplantation / Sugerencias de orientaciones para alta de niños en el pos trasplante de células madres hematopoyéticas

Estudo qualitativo descritivo com sugestões de aprimoramento de orientações para a alta hospitalar de crianças no pós-transplante de células-tronco hematopoiéticas. Realizado em serviço público de transplante de medula óssea do sul do Brasil com 58 participantes, entre eles profissionais da equipe multiprofissional e familiares cuidadores, entrevistados de janeiro de 2014 a março de 2016. Utilizou-se a análise de conteúdo temático categorial. As possibilidades de aprimoramento são capacitação dos profissionais envolvidos no cuidado, construção e aplicação de planejamento de alta pela equipe multiprofissional, inclusão da criança na orientação, utilização de formas variadas para orientar, e elaboração de material didático apropriado. O processo de alta hospitalar é complexo e a equipe envolvida na assistência ao paciente e cuidador é responsável por tornar esse momento de transição um período de aprendizagem, para auxiliá-los nos cuidados em casa (AU).

Qualitative descriptive study with suggestions for the improvement of guidelines for hospital discharge of children in post-hematopoietic stem cell transplantation. The study was conducted in a public service specialized in bone marrow transplantation in southern Brazil, with 58 participants, including professionals of the multidisciplinary team and family caregivers, interviewed in the January 2014-March 2016 period. Thematic content analysis was used. The possibilities of improvement identified here are as follows: training of the professionals involved in care, construction and implementation of discharge planning by the multidisciplinary team, guidance provided also to the patients (children), use of various ways to guide and prepare the appropriate teaching materials. The discharge process is complex, and the staff that supports patients and caregivers is responsible for turning this moment of transition of care from hospital to home into a period of learning, assisting them in home care (AU).

Estudio cualitativo descriptivo que trae sugerencias de perfeccionamiento de orientaciones para el alta hospitalar de niños en el pos trasplante de células madres hematopoyéticas. Fue realizado en el servicio público de trasplante de médula osea en sur de Brasil con 58 participantes, entre profesionales del equipo multiprofesional y familiares cuidadores. Estos fueron entrevistados de enero de 2014 a marzo de 2016. Se utilizó el análisis de contenido temático categorial. Las posibilidades de perfeccionamiento son capacitación de los profesionales participantes en cuidado, construcción y aplicación de planeamiento de alta por el equipo multiprofesional, inclusión del niño en la orientación, uso de formas distintas para orientar y elaboración de material didático adecuado. El proceso de alta hospitalaria es complejo, y el equipo integrado en la asistencia al paciente y cuidador es responsable por ayudar en los cuidados en casa y para que ese momento de transición sea un periodo de aprendizado (AU).

A vivência do cuidado familiar em casas transitórias de apoio / La vivencia del cuidado familiar en casas transitorias de apoyo / The experience of family care in transitional support houses

RESUMO Objetivo: apresentar modelo teórico representativo da vivência do cuidado em casas transitórias de apoio a familiares de crianças em pós-transplante de células-tronco hematopoiéticas. Método: Teoria Fundamentada nos Dados, realizada com 18 participantes de três grupos amostrais. Para análise, utilizou-se o software QSR Nvivo10. Resultados: elaboraram-se quatro categorias: residindo em casa transitória de apoio; vivenciando o cuidado à criança em pós-transplante de células-tronco hematopoiéticas; cuidando do cuidador familiar; e retornando a uma nova vida no lar, as quais se inter-relacionam conforme o código teórico da família interativa. Conclusão: esta pesquisa contribui para compreensão da vivência do cuidado em casas transitórias de apoio a familiares de crianças em pós-transplante de células-tronco hematopoiéticas e subsidia as ações de enfermagem e saúde prestadas a esta população; contribui ainda para a elaboração de orientação de alta hospitalar e cuidado direcionado a essa clientela.

RESUMEN Objetivo: presentar un modelo teórico representativo de la vivencia del cuidado en casas transitorias de apoyo a familiares de niños en pos-trasplante de células madre hematopoyéticas. Método: Teoría Fundamentada en Datos, realizada con 18 participantes de tres grupos muestrales. Para el análisis, se utilizó el software QSR Nvivo10. Resultados: se elaboraron cuatro categorías: residiendo en casa transitoria de apoyo; vivir el cuidado al niño en pos-trasplante de células madre hematopoyéticas; cuidando del cuidador familiar; y retornando a una nueva vida en el lar, las cuales se inter-relacionan de acuerdo con el código teórico de la familia reactiva. Conclusión: esta investigación contribuye para la comprensión de la vivencia del cuidado en casas transitorias de apoyo a familiares de niños en pos-trasplante de células madre hematopoyéticas y subvenciona las acciones de enfermería y salud prestadas a esta población; aún contribuye para la elaboración de orientación de alta hospitalaria y cuidado direccionado a estos clientes.

ABSTRACT Objective: to present the theoretical model that represents the experience of care in transitional homes of support to families of children in a period of post-transplantation of hematopoietic stem cells. Method: grounded theory, performed with 18 participants from three different samples. For analysis, we used the QSR Nvivo10 software. Results: we elaborated four categories: living in the transitional support home; experiencing care of children in post-transplantation of hematopoietic stem cells; taking care of the family caregiver; and returning to a new life at home, which interrelate according to the theoretical code of the interactive family. Conclusion: this research contributes to understanding the experience of care in transitional support homes of families with children in post-transplantation of hematopoietic stem cells and subsidizes nursing and health actions provided to this population; it also contributes to the development of a hospital discharge guidance and care directed to this clientele.

Transplante de células-tronco hematopoiéticas de crianças em cuidado ambulatorial: perfil sociodemográfico e clínico / Hematopoietic stem cell transplantation of children in outpatient care: sociodemographic and clinical profile

Resumo: Este estudo objetivou identificar o perfil sociodemográfico e clínico de crianças em pós-transplante de células-tronco hematopoiéticas imediato em cuidado ambulatorial. Pesquisa quantitativa, transversal e retrospectiva, realizada no Serviço de Transplante de Medula Óssea do Complexo Hospital de Clínicas da Universidade Federal do Paraná. Dentre os critérios de inclusão estão prontuários de crianças com idade entre 0 e 12 anos incompletos, transplantadas no período de 2009 a 2013. Os dados foram coletados por meio de instrumento estruturado, com início em janeiro e término em julho de 2015, e analisados por métodos estatísticos simples com auxílio do programa Software Statistical Package for the Social Sciences® 19.0. Para avaliação da associação entre variáveis categóricas foi aplicado o Teste do qui-quadrado, sendo considerados os valores de p<0,05 com significância estatística. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa do Setor de Ciências da Saúde da Universidade Federal do Paraná, parecer 742.621, 07 de agosto/2014. A amostra foi composta por 138 prontuários, dos quais 66,7% do sexo masculino, 58,5% com idade igual ou superior a seis anos, 51,4% estudantes, 68,1% brancos e 68,1% católicos. Houve prevalência das síndromes de falência medular (51%), dentre as quais a Anemia de Fanconi (30,4%). Todos os transplantes foram alogênicos, sendo 51,4% não aparentados. A medula óssea foi a fonte de células-tronco mais utilizada (80,4%), seguida do sangue de cordão umbilical (19,6%). Os transplantes com doadores aparentados incompatíveis somaram 12,3%. Dos transplantes, 69,6% foram compatíveis, prevaleceu o condicionamento de intensidade reduzida (50,7%) e a mucosite apresentou prevalência de 92,8%. Colonização por microrganismos multirresistentes esteve presente em 26,1%. As perdas do cateter de Hickman somaram 8% e o uso de sonda nasoenteral 11,6%. A alta hospitalar ocorreu, em 61,6%, entre 21 e 30 dias após o transplante. As reinternações somaram 34,8%, sendo a febre a principal causa (23,9%). Quanto às intercorrências clínicas, as mais prevalentes foram dor (60,9%), tosse (57,2%), coriza e febre (47,1% cada), vômito (46,4%), náusea (35,5%), diarreia (39,1%) e infecção viral (37%). Esta última esteve relacionada a sintomas como tosse, coriza e febre, bem como com a incompatibilidade do antígeno leucocitário humano (p<0,05). Houve associação entre transplantes com sangue de cordão umbilical e infecção viral; e transplantes não aparentados e infecções fúngicas e virais. A doença do enxerto contra hospedeiro representou 26,8%, sendo a pele o órgão mais acometido (11,6%). Um total de 68,1% de participantes necessitou de antibiótico e a causa mais comum foi a febre (43,5%). Quanto aos antivirais, 51,4% utilizaram e a principal causa foi o Citomegalovírus (45,7%). A rejeição do enxerto aconteceu em 13%. Dos participantes, 42,8% realizaram até 5 transfusões e a reação transfusional somou 8,6%. A alta ambulatorial aconteceu após os 100 dias do transplante em 56,5%. Almeja-se que estes dados possam corroborar o desenvolvimento de estratégias de cuidado, criação de protocolos e capacitação da equipe para atender a essa população de crianças, a partir das necessidades identificadas, bem como contribuir com o desenvolvimento da prática profissional em transplante de células-tronco hematopoiéticas.

Abstract: This study aimed to identify the sociodemographic and clinical profile of children in post-hematopoietic stem cells transplantation in outpatient care. This is a quantitative, transversal, and retrospective research, carried out at the Bone Marrow Transplant Service of the Clinics Hospital Complex of the Federal University of Paraná, Paraná State, Brazil. Records of children aged from 0 to incomplete 12 years old, transplanted from 2009 to 2013, were among the criteria of inclusion. Data were collected using a structured instrument, beginning in January and ending in July 2015, and were analyzed using Statistical Package for the Social Sciences® (SPSS) software, version 19. Chi-square test was applied to evaluate the association among categorical variables, and p<0.05 values were considered as statistical significance. This study was approved by the Research Ethics Committee of the Health Sciences Sector of the Federal University of Paraná, under Opinion n. 742,621 of 7 August 2014. One hundred thirty-eight medical records composed the sample; among them, 66.7% were male patients, 58.5% were equal or greater than six years old, 51.4% were students, 68.1% were white, and 68.1% were Roman Catholic. There was prevalence of bone marrow failure syndromes (51%), and the Fanconi anemia (30.4%) was among them. All of the transplants were allogeneic, and 51.4% were unrelated. The bone marrow was the most used source of stem cells (80.4%), followed by umbilical cord blood (19.6%). Transplants with mismatched related donors were 12.3%. Compatible transplants were 69.6%; reduced intensity conditioning (50.7%) was prevailed; and mucositis showed a prevalence of 92.8%. Colonization by multi-resistant microorganisms was present in 26.1% of the cases. Losses of the Hickman catheter were 8% and the use of nasogastric probe was 11.6%. The hospital discharge occurred in 61.6% in the period of 21 to 30 days after transplantation. Hospitalizations accounted for 34.8%, and the main cause was fever (23.9%). Regarding clinical complications, the most prevalent were pain (60.9%), cough (57.2%), runny nose and fever (47.1% each one), vomiting (46.4%), nausea (35.5%), diarrhea (39.1%), and viral infection (37%). Viral infection was related to symptoms such as coughing, runny nose and fever, as well as related to the incompatibility of the human leukocyte antigen (p<0.05). There was association among umbilical cord blood transplants and viral infection; and unrelated transplants were associated with fungal and viral infections. The graft-versus-host disease accounted for 26.8%, and the skin is the most affected organ (11.6%). A total of 68.1% of participants needed antibiotic and the most common cause was fever (43.5%). The main cause of viral infections was the Cytomegalovirus (45.7%), and antivirals were used in 51.4% of the cases. The graft rejection occurred in 13% of the transplants. A total of 42.8% of participants had up to five blood transfusions and 8.6% had transfusion reaction. The outpatient discharge of 56.5% took place after hundred days of transplant. It is expected that this data can confirm the development of care strategies, creation of protocols, and staff training to address this children population, considering the identified needs; it is expected also that it can contribute to the development of professional practice in hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation in the elderly. Predicting the risk for non relapse mortality.

We have retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplantation (HSCT) between January 1997 and July 2013. Median follow up was 1.3 years. Sex, age, diagnosis, disease stage, comorbidities (according to HCT-CI score), type of donor, histocompatibility, conditioning regimen and graft-versus-host disease (GVHD) prophylaxis were evaluated. The incidence and severity of acute and chronic GVHD, overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and relapse were investigated according those variables. Acute GVHD incidence was 41% (7.3% GIII-IV). Patients with acute myeloid leukemia had lesser aGVH GII-IV (14% vs. 35%, p<0.01) comparing to the entire population. Extensive cGVHD incidence was 9.4%. Global OS 1-3 years was 44-20%, DFS 33-20%, relapse 35-41% and NRM 36-43% respectively. The presence of comorbidities showed a significant increase in NRM (CT-CI 0 vs. 1 vs ≥2: 1-3 years 17-24% vs. 40-46% vs. 45-67%, p=0.001, MA HR 2.03, CI 95% 1.02-5.29), as well as cyclosporine vs. tacrolimus (1-3 years 47-53% vs. 25-36%, p=0.01). Tacrolimus patients had higher 1-3 years OS (49-25% vs. 31-13%, p=0.01) and DFS (41-26% vs. 20-11%, p<0.01). Age, type of donor and myeloablative conditioning showed no significant differences in any outcome. Allogeneic HSCT is a valid therapeutic option for older patients in Argentina. The main risk factor for a significantly increased NRM and a trend to inferior OS was the number of comorbidities. Age was not a factor for a worse result. The other factor having a significant effect in better outcome was tacrolimus administration.

Allogeneic hematopoietic stem cell transplantation in the elderly: Predicting the risk for non relapse mortality

We have retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplantation (HSCT) between January 1997 and July 2013. Median follow up was 1.3 years. Sex, age, diagnosis, disease stage, comorbidities (according to HCT-CI score), type of donor, histocompatibility, conditioning regimen and graft-versus-host disease (GVHD) prophylaxis were evaluated. The incidence and severity of acute and chronic GVHD, overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and relapse were investigated according those variables. Acute GVHD incidence was 41% (7.3% GIII-IV). Patients with acute myeloid leukemia had lesser aGVH GII-IV (14% vs. 35%, p < 0.01) comparing to the entire population. Extensive cGVHD incidence was 9.4%. Global OS 1-3 years was 44-20%, DFS 33-20%, relapse 35-41% and NRM 36-43% respectively. The presence of comorbidities showed a significant increase in NRM (CT-CI 0 vs. 1 vs ≥ 2: 1-3 years 17-24% vs. 40-46% vs. 45-67%, p = 0.001, MA HR 2.03, CI 95% 1.02-5.29), as well as cyclosporine vs. tacrolimus (1-3 years 47-53% vs. 25-36%, p = 0.01). Tacrolimus patients had higher 1-3 years OS (49-25% vs. 31-13%, p = 0.01) and DFS (41-26% vs. 20-11%, p < 0.01). Age, type of donor and myeloablative conditioning showed no significant differences in any outcome. Allogeneic HSCT is a valid therapeutic option for older patients in Argentina. The main risk factor for a significantly increased NRM and a trend to inferior OS was the number of comorbidities. Age was not a factor for a worse result. The other factor having a significant effect in better outcome was tacrolimus administration.

Se efectuó un análisis retrospectivo de 137 historias clínicas de pacientes mayores de 50 años que recibieron un trasplante alogénico de precursores hematopoyéticos (TAPH). Se evaluaron las siguientes características: sexo, edad, enfermedad, estadio, comorbilidades (según el HCT-CI), donante, acondicionamiento e inmunosupresión. Se analizó la incidencia de enfermedad injerto vs. huésped aguda (aEICH) y crónica (cEICH), supervivencia global (SG), supervivencia libre de enfermedad (SLE), recaída y mortalidad libre de enfermedad (MLE). Los trasplantes fueron realizados entre 1997-2013, mediana de seguimiento 1.3 años. La incidencia de aEICH fue de 41% (7.3% GIII-IV). Los pacientes con leucemia mieloide aguda presentaron menor incidencia de EICHa GII-IV (14% vs. 34%, p < 0.01). La incidencia de EICHc extenso fue de 9.4%. La SG a 1-3 años fue 44-20%, SLE 33-20%, recaída 35-41% y la MLE 36-43%. Los pacientes con comorbilidades tuvieron un aumento significativo de la MLE (HCT-CI 0 vs. 1 vs. ≥2: 1-3 años 17-24% vs. 40-46% vs. 45-67%, p = 0.001, AMV HR 2.03, IC 95% 1.02-5.29), al igual que el uso de ciclosporina vs. tacrolimus (1-3 años 47-53% vs. 25-36%, p = 0.01). Los pacientes que recibieron tacrolimus tuvieron una mayor SG (1-3 años 49-25% vs. 31-13%, p = 0.01) y SLE (1-3 años 41-26% vs. 20-11%, p < 0.01). La edad, tipo de donante y acondicionamiento no resultaron significativos para ningún evento. El TAPH es una herramienta terapéutica válida en pacientes mayores. Los factores pronósticos que inciden mayormente en el trasplante son las comorbilidades y no la edad. El otro factor que demostró un efecto significativo fue el uso de tacrolimus.

Carga de trabalho de enfermagem em transplante de células-tronco hematopoiéticas: estudo de coorte / Carga del trabajo de enfermería en trasplante de células madre hematopoyéticas: estudio de cohorte / Nursing workload in hematopoietic stem cell transplantation: a cohort study

RESUMO Objetivo Mensurar a carga de trabalho de enfermagem requerida por pacientes submetidos ao transplante de células-tronco hematopoiéticas (TCTH), autólogo e alogênico e analisar as atividades do Nursing Activities Score (NAS) executadas pela equipe de enfermagem durante a internação para o TCTH. Método Coorte prospectiva realizada de janeiro/2013 a abril/2014 com 62 pacientes internados na unidade de TCTH de um hospital universitário de Campinas/SP, Brasil. Mediu-se a carga de trabalho por meio do NAS e analisaram-se os dados utilizando os testes Qui-quadrado ou Exato de Fisher, Mann-Whitney e o coeficiente de correlação de Spearman; considerou-se nível de significância de 5%. Resultados A média da carga de trabalho de enfermagem foi de 67,3% (DP 8,2) em pacientes de TCTH autólogo e de 72,4% (DP 13,0) no TCTH alogênico (p=0,1380). O item Monitorização e controles apontou, em mais de 50% das observações, que os pacientes demandaram intensificação deste cuidado, exigindo duas horas ou mais em algum turno de trabalho por motivos de segurança, gravidade ou terapia. Conclusão A carga de trabalho de enfermagem e os itens do NAS mais pontuados refletem a magnitude, complexidade e especificidade dos cuidados demandados pelos pacientes submetidos ao TCTH.

RESUMEN Objetivo Medir la carga de trabajo de enfermería requerida por los pacientes sometidos al trasplante de células madre hematopoyéticas (TCTH), autólogo y alogénico, analizando actividades del Nursing Activities Score (NAS) emprendidas por equipo de enfermería en la internación para el TCTH. Método Cohorte prospectiva realizada entre enero/2013 y abril/2014 con 62 pacientes internados en la unidad de TCTH de hospital universitario en la ciudad de Campinas/SP (BR). En el análisis se utilizaron las pruebas Chi-cuadrado o test Exacto de Fisher, las no paramétricas Mann-Whitney o Kruskal-Wallis y el coeficiente de correlación de Spearman, conforme apropiado. Fijos los niveles de significación en 5%. Resultados La media de la carga de trabajo fue de 67,3% (DP 8,2) para los pacientes de TCTH autólogo y de 72,4% (DP 13,0) para los de TCTH alogénico (p=0,1380). El ítem Monitorización y controles apuntó que los pacientes, en más 50% de las observaciones, demandaban intensificación del cuidado por dos horas o más en algunos turnos de trabajo por cuestiones de seguridad, gravedad o terapia. Conclusión La carga de trabajo en enfermería y los ítems del NAS puntuados reflejan la magnitud, complejidad y especificidad de los cuidados demandados por los pacientes sometidos al TCTH.

ABSTRACT Objective Measure nursing workload required by patients submitted to autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and analyze the Nursing Activities Score (NAS) of the nursing team during the hospitalization period for HSCT. Method A prospective cohort study conducted from January 2013 to April 2014 with 62 patients hospitalized in the HSCT unit of a university hospital in Campinas, São Paulo, Brazil. The workload was measured through NAS and data analysis was through chi-square test or Fisher’s exact test, Mann-Whitney test and Spearman’s correlation coefficient; with 5% significance level. Results Mean nursing workload was 67.3% (SD of 8.2) in autologous HSCT patients and 72.4% (SD of 13.0) in allogeneic HSCT patients (p=0.1380).Monitoring and titration showed, in more than 50% of the time, patients demanded intensified care, requiring two hours or more in a nursing shift for reasons of safety, severity or therapy. Conclusion The nursing workload and the NAS items with the highest scores reflect the magnitude, complexity and specificity of care required by patients submitted to HSCT.

Turismo con células madre y requisitos para su uso clínico: desafíos bioéticos más allá del embrión / Bioethical challenges of stem cell tourism

Stem cells have drawn extraordinary attention from scientists and the general public due to their potential to generate effective therapies for incurable diseases. At the same time, the production of embryonic stem cells involves a serious ethical issue concerning the destruction of human embryos. Although adult stem cells and induced pluripotential cells do not pose this ethical objection, there are other bioethical challenges common to all types of stem cells related particularly to the clinical use of stem cells. Their clinical use should be based on clinical trials, and in special situations, medical innovation, both of which have particular ethical dimensions. The media has raised unfounded expectations in patients and the public about the real clinical benefits of stem cells. At the same time, the number of unregulated clinics is increasing around the world, making direct offers through Internet of unproven stem cell therapies that attract desperate patients that have not found solutions in standard medicine. This is what is called stem cells tourism. This article reviews this situation, its consequences and the need for international cooperation to establish effective regulations to prevent the exploitation of patients and to endanger the prestige of legitimate stem cell research.

Qualidade de vida relacionada à saúde de pacientes com esclerose múltipla antes do transplante de células-tronco hematopoéticas / Health related quality of life of patients with multiple sclerosis before hematopoietic stem cells transplantation

Este estudo teve por objetivo avaliar qualidade de vida (QV) e vulnerabilidade psicológica (ansiedade, depressão e estresse) de pacientes com Esclerose Múltipla (EM) que seriam submetidos ao Transplante de Células-Tronco Hematopoéticas (TCTH). Participaram do estudo 13 pacientes. Os instrumentos utilizados foram: Questionário Genérico de Avaliação de Qualidade de Vida - SF-36, Escala Hospitalar de Ansiedade e Depressão (HAD) e Inventário de Sintomas de Stress para Adultos de Lipp (ISSL). A análise dos dados foi realizada segundo as recomendações específicas de cada instrumento. Os resultados evidenciaram a existência de relação significativa entre prejuízos físicos e mentais impostos pela enfermidade (e/ou pelo transplante) e a instalação de quadros de depressão, ansiedade e estresse nos participantes.

This study aimed to evaluate quality of life (QoL) and psychological vulnerability (anxiety, stress and depression) of patients with multiple sclerosis (MS) who would undergo Hematopoietic Stem Cell Transplantation (HSCT). The sample consisted of 13 patients. The following instruments were used: MOS 36-Item Short-Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HAD) and Lipp's Stress Symptoms Inventory for Adults (ISSL). Data analysis was performed according to specific recommendations for each instrument. The obtained results showed that the physical and mental damage the illness (and/or transplantation) imposed is significantly related with the emergence of depression, anxiety and stress in participants.

Qualidade de vida relacionada à saúde de pacientes com esclerose múltipla antes do transplante de células-tronco hematopoéticas / Health related quality of life of patients with multiple sclerosis before hematopoietic stem cells transplantation

Este estudo teve por objetivo avaliar qualidade de vida (QV) e vulnerabilidade psicológica (ansiedade, depressão e estresse) de pacientes com Esclerose Múltipla (EM) que seriam submetidos ao Transplante de Células-Tronco Hematopoéticas (TCTH). Participaram do estudo 13 pacientes. Os instrumentos utilizados foram: Questionário Genérico de Avaliação de Qualidade de Vida - SF-36, Escala Hospitalar de Ansiedade e Depressão (HAD) e Inventário de Sintomas de Stress para Adultos de Lipp (ISSL). A análise dos dados foi realizada segundo as recomendações específicas de cada instrumento. Os resultados evidenciaram a existência de relação significativa entre prejuízos físicos e mentais impostos pela enfermidade (e/ou pelo transplante) e a instalação de quadros de depressão, ansiedade e estresse nos participantes.(AU)

This study aimed to evaluate quality of life (QoL) and psychological vulnerability (anxiety, stress and depression) of patients with multiple sclerosis (MS) who would undergo Hematopoietic Stem Cell Transplantation (HSCT). The sample consisted of 13 patients. The following instruments were used: MOS 36-Item Short-Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HAD) and Lipp's Stress Symptoms Inventory for Adults (ISSL). Data analysis was performed according to specific recommendations for each instrument. The obtained results showed that the physical and mental damage the illness (and/or transplantation) imposed is significantly related with the emergence of depression, anxiety and stress in participants.(AU)

Dietary recommendations for immunosuppressed patients of 17 hematopoietic stem cell transplantation centers in Brazil.

INTRODUCTION: Low-microbial diets are recommended to reduce the risk of foodborne infections when hematopoietic stem cell transplantation patients have neutropenia. However there is no pattern concerning the composition of such a diet. OBJECTIVE: To collect information concerning the structure of nutrition departments and the diets recommended for immunosuppressed patients in transplant centers in Brazil. METHODS: Questionnaires were sent to the 45 Bone Marrow Transplantation Centers listed by the Sociedade Brasileira de Transplante de Medula Óssea (SBTMO). Completed questionnaires were returned by 17 centers. The questions were related to the profile and the structure of the nutrition department, at what point a general diet is allowed after transplantation, and which food is allowed during the critical period of immunosuppression and soon after transplantation. RESULTS: Of the 17 centers that participated, 82% have a professional nutritionist exclusively for the Transplant Department but only 41% have an area specifically for the preparation of diets for immunosuppressed patients. The patients are released from the low-microbial diet to general diets 90-100 days after allogeneic hematopoietic stem cell transplantation by 29% of the centers and only after suspension of immunosuppressive drugs in 24%. Most centers (88%) restrict the consumption of raw fruits, all restrict the consumption of raw vegetables and 88% forbid the consumption of yogurt in the critical period of immunosuppression. There was no consensus on forbidden foods soon after transplantation. CONCLUSION: Major differences in diets recommended to hematopoietic stem cell transplantation patients were observed between the different centers.

Profilaxis antifúngica en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against fungal infections in solid organ and hematopoietic stem cells transplantation

Invasive fungal infections are an important cause of morbidity and mortality in SOT and HSCT recipients. The main species involved are Candida spp. and Aspergillus spp, less frequently Cryptococcus spp., causal agents of mucormycosis and Fusarium spp. Usually occur within the first six months post-transplant, but they do it later, especially during episodes of rejection, which maintains the state of immune system involvement. Prophylaxis recommendations are specific to each type of transplant. In liver transplantation use of fluconazole is recommended only in selected cases by high risk factor for invasive fungal infections (A1). If the patient has a high risk of aspergillosis, there are some suggestions for adults population to use amphotericin B-deoxycholate, liposomal amphotericin B or caspofungin (C2) without being validated none of these recommendations in pediatric population. In adult lung transplant patients where the risk of aspergillosis is higher than in other locations, we recommend universal prophylaxis with itraconazole 200 mg/day, nebulised liposomal amphotericin B or voriconazole (C2), no validated recommendations for pediatrics. In HSCT, universal prophylaxis is recommended only in allogeneic and autologous selected cases. The most accepted indication is fluconazole (A1), and posaconazole (A1) or micafungin (A1) in selected cases with high risk of aspergillosis.

Las infecciones fúngicas invasoras constituyen una importante causa de morbilidad y mortalidad en los pacientes receptores de TOS y TPH. Los principales agentes involucrados son Candida spp. y Aspergillus spp, menos frecuentemente Cryptococcus spp., agentes causales de mucormicosis y Fusarium spp. Se presentan habitualmente dentro de los primeros seis meses posttrasplante, pero también lo hacen en forma más tardía, especialmente durante episodios de rechazo, en que se mantiene el estado de compromiso del sistema inmune. Existen recomendaciones de proilaxis especíicas para cada tipo de trasplante. En trasplante hepático se recomienda el uso de fluconazol sólo en casos seleccionados por factores de riesgo (A1). Si existe riesgo de asper-gilosis, hay algunas sugerencias en adultos para el uso de anfotericina B-deoxicolato, anfotericina liposomal o caspofungina (todo en categoría C2), sin estar validada ninguna de estas recomendaciones en pediatría. En trasplante pulmonar en paciente adulto, donde el riesgo de aspergilosis es superior a otras localizaciones, se recomienda proilaxis universal, con itraconazol 200 mg/día, anfotericina liposomal nebulizada o voriconazol (C2), sin recomendaciones validadas para pediatría. En TPH, se recomienda proilaxis universal en trasplante alogénico y sólo para casos seleccionados en trasplantes autólogos. La indicación más aceptada es fluconazol (A1), siendo alternativas a evaluar dependiendo del riesgo de aspergilosis, posaconazol (A1) y micafungina (A1).

Profilaxis de neumonía por Pneumocystis jiroveci en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against Pneumocystis pneumonia in pediatric and adult patients undergoing solid organ or hematopoietic stem cells transplantation

Pneumocystis jiroveci is an important pathogen in patients undergoing SOT and HSCT. Universal prophylaxis is recommended for all adults and children with SOT and HSCT, considering that its use significantly reduces the occurrence and mortality associated with pneumonia by this agent. The drug of choice is cotrimoxazole (A1) three times a week, low-dose scheme, that has proved equally effective and better tolerated than the daily regimen and/or at high doses. Prophylaxis starts 7 to 14 days post transplant in SOT recipients and post-implant in HSCT, with an average duration of 6 months except in liver and lung transplant as in HSCT with significant degree of immunosuppression, that lasts for 1 year. Alternatives for prophylaxis are dapsone (B2), aerosolized pentamidine (B2) and atovaquone (C2).

Pneumocystis jiroveci es un patógeno importante en pacientes sometidos a TOS y TPH. Se recomienda proilaxis universal a todos los pacientes adultos y niños sometidos a TOS o TPH porque su uso reduce signiicati-vamente la ocurrencia y mortalidad asociada a neumonía por este agente. El medicamento de elección es cotrimoxa-zol (A1) tres veces por semana, en dosis bajas, esquema que ha demostrado igual eicacia y mejor tolerancia que el esquema diario y/o con dosis altas. La proilaxis se inicia 7 a 14 días post trasplante en TOS y posterior al implante en TPH, con una duración promedio de 6 meses salvo en trasplante de hígado y pulmón en que se prolonga por 1 año, al igual que en TPH con grado importante de inmunosupresión. Son alternativas de profilaxis dapsona (B2), pentamidina aerosolizada (B2) y atavacuona (C2).

Profilaxis de citomegalovirus en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against cytomegalovirus infection in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation

CMV is one of the main infectious problems for SOT and HSCT. The severity of the complications are mainly associated with the type of transplant and immune status against the virus of the transplant donor and the transplant recipient. It is important to prevent exposure, using safe blood transfusion CMV seronegative donors (B1) and/or use of blood leucocytes-depleted by filtration (Al). In addition to preventing exposure, there are two widely used prevention strategies: universal prophylaxis with antiviral therapy or "pre-emptive" strategy based on the use of antivirals only to the early detection of CMV replication in blood. The first option is most used in the SOT management, especially for those identified as the high risk group of CMV disease: R (+), with D (+) or D (-) (Al), where the recommended drug is ganciclovir or valganciclovir . The second approach is preferable for HSCT, which recommends weekly monitoring for CMV viral load from day 10 to 100 post transplant (A3). This strategy requires having a viral laboratory support (A2). The selected antiviral in the case of pre emptive therapy is intravenous ganciclovir (A1).

La infección y enfermedad por CMV son problemas comunes en pacientes con TOS y TPH. La gravedad de las complicaciones asociadas a este virus dependen fundamentalmente del tipo de trasplante y de la experiencia inmunológica previa contra el virus del donante y el receptor. Es importante prevenir la exposición, utilizando transfusiones de sangre segura para CMV con donantes seronegativos (B1) y/o uso de sangre leuco-depletada por iltración (A1). Además de prevenir la exposición, existen dos estrategias de prevención ampliamente utilizadas: La proilaxis universal con antivirales y la terapia adelantada o estrategia "pre-emptive" basada en el uso de antivirales sólo ante la detección precoz de replicación del CMV en sangre. La primera opción es de mayor uso en TOS, especialmente para aquellos binomios identficados como de mayor riesgo de enfermedad por CMV: R (+), con D (+) o D (-) (A1), siendo el medicamento recomendado ganciclovir o valganciclovir. La segunda opción es de elección en TPH, en cuyo caso se recomienda monitoreo semanal con carga viral para CMV desde el día 10 al 100 post trasplante (A3), lo que implica contar con un laboratorio de apoyo en diagnóstico virológico (A2). El antiviral de elección en este caso es ganciclovir iv (A1).

Profilaxis de enfermedad por virus de Epstein Barr en niños y adultos receptores de trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against Epstein Barr disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation

Post transplant lymphoproliferative disease (PTLD) associated with EBV infection is one of the most life-threatening complications in SOT and HSCT. Risk factors for infection or reactivation of EBV in SOT are the use of greater immunosuppression, seronegative receptor and CMV infection. In HSCT, the risk factors are related to type of transplant, HLA disparity, the greater immunosuppression, T-cell depletion and severe GVHD. There is no scientific evidence to support the use of specific therapy for prophylaxis of EBV infection. Prophylaxis recommendations focus on avoid exposure of transplant recipients to sources of virus, through hygiene practices such as hand washing (A3), avoid sharing utensils (B3) and avoid contact with potentially infected secretions (respiratory or saliva) (A2). For PTLD prevention, the recommendation is regular EBV viral load monitoring by rtPCR. In SOT with logarithmic rising of EBV loads, it is recommended to reduce immunosuppression and periodically perform exams to diagnose PTLD. In HSCT, it is recommended to reduce immunosuppression whenever possible, and use rituximab according to speciic protocol. Acyclovir or gancyclovir have not proven to be of any eficacy in PTLD prophylaxis in SOT (C3) or HSCT (D2), so their administration as preemptive therapy is no recommended.

El síndrome linfoproliferativo (SLP) asociado a VEB constituye una grave complicación en TOS y en TPH. Los factores de riesgo de infección o reactivación de VEB en TOS son el uso de mayor inmunosupresión, la seronegatividad del receptor previa al trasplante y la infección por CMV. En TPH se consideran factores de riesgo el tipo de trasplante, disparidad HLA, mayor inmunosupresión, depleción linfocitaria y enfermedad injerto contra hospedero (EICH) grave. No hay evidencia cientíica que apoye el uso de medidas especíicas de proilaxis en prevención de infección por VEB. Se recomienda evitar la exposición a fuentes del virus de los candidatos a trasplantes a través de prácticas de higiene tales como lavado de manos (A3), evitar el compartir utensilios (B3) y evitar el contacto con potenciales secreciones infectadas (respiratorias o saliva) (A2). Para la prevención de SLP, se recomienda un esquema de monitoreo periódico de carga viral de VEB por RPC-TR. En el caso de TOS con cargas de VEB en ascenso logarítmico, se recomienda disminuir inmuno-supresión y buscar activa y periódicamente la aparición de SLP. En TPH, se recomienda, en lo posible, disminuir la inmunosupresión y se reserva el uso de rituximab para casos especíicos según protocolo. El uso de aciclovir o ganciclovir no han demostrado constituir medidas profilácticas efectivas en TOS (C3) ni en TPH (D2), no siendo recomendada su administración en esquemas de terapia anticipada.

Profilaxis de infección por virus respiratorios en niños y adultos sometidos a trasplante de órganos sólidos y precursores hematopoyéticos / Prophylaxis against respiratory viral disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation

Respiratory viruses have been identified as a cause of morbidity and mortality in patients undergoing SOT and HSCT, specially in children. The most frequent are respiratory syncytial virus (RSV), influenza (FLU), parainfluenza (PI) and adenovirus (ADV). These infections are associated with progression to severe lower respiratory tract infections in up to 60% of the cases. It is advised to apply universal protection recommendations for respiratory viruses (A2) and some specific measures for FLU and AD. FLU: Annual anti-influenza vaccination (from 4-6 months post-transplantation in SOT, 6 months in HSCT (A2)); post- exposure prophylaxis in FLU (oseltamivir for 10 days (B2)). In lung transplantion, the prophylaxis should last as long as the risk period (B2). ADV: There is no vaccine nor valid chemoprophylaxis strategy to prevent ADV disease. In some specific HSCT recipients, weekly PCR monitoring is recommended until day+100 (A3).

Los virus respiratorios se han identificado como causa de morbi-mortalidad en pacientes sometidos a TOS y TPH, particularmente en pediatría. Los más frecuentes son virus respiratorio sincicial (VRS), influenza (FLU), parainfluenza (PI) y adenovirus (ADV). La fuente de contagio está en la comunidad y en el hospital afectando al paciente en cualquier período post-trasplante. Se describe progresión a infecciones graves del tracto respiratorio bajo hasta en 60 % de los casos. Se recomienda aplicar medidas de aislamiento de precaución universal para todos los virus respiratorios (A2) y se describen algunas medidas específicas para FLU y AlDV. Vacunación anti-influenza anual con vacuna inactivada (en TOS a partir de 4-6 meses post-trasplante (A2), en TPH a partir de 6 meses (A2)); profilaxis post exposición a virus FLU (oseltamivir durante 10 días (B2)). En trasplante de pulmón, la duración de la profilaxis se extenderá mientras dure el período de riesgo (B2). Con respecto a ADV, no se dispone de una vacuna adecuada y no existe a la fecha una estrategia validada de quimioprofilaxis para prevenir enfermedad por ADV; en casos específicos de TPH pediátrico, se recomienda vigilancia semanal con RPC en sangre periférica hasta el día +100 post-TPH (A3).