RESUMEN
Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage-; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage-, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Células Dendríticas/patología , Enfermedad Injerto contra Huésped/mortalidad , Neoplasias Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante , Enfermedad Aguda , Adolescente , Adulto , Anciano , Recuento de Células , Linaje de la Célula/inmunología , Niño , Preescolar , Células Dendríticas/clasificación , Células Dendríticas/inmunología , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/terapia , Humanos , Inmunosupresores/uso terapéutico , Lactante , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Hermanos , Análisis de Supervivencia , Trasplante Homólogo , Donante no EmparentadoRESUMEN
Failure-free survival (FFS), defined as the absence of new systemic treatment, recurrence of original malignancy and mortality not associated with recurrence after allogeneic hematopoietic stem cell transplantation (HCT), is a robust clinical measure to interpret results of initial systemic treatment of chronic graft-versus-host disease (cGVHD). We evaluate FFS after initial treatment of cGVHD in a mixed-race cohort from a resource-constrained country. This retrospective study included 354 consecutive patients after their first HCT between January 2014 and August 2020, who received initial systemic treatment for moderate or severe cGVHD at 13 Brazilian centers. Cox regression models were used to identify risk factors for treatment failure. The overall median follow-up among survivors was 28 months (range 1-71) after initial treatment. FFS was 89% at 6 months, 71% at 1 year and 52% at 2 years. New systemic treatment was the major cause of failure. In multivariable models, prior grades II-IV acute GVHD, a National Institutes of Health severity score of 3 in liver, gastrointestinal tract or lung involvement, and onset of initial treatment of cGVHD within 12 months after transplantation were all associated with an increased risk of treatment failure. Our results could serve as a benchmark for the design of future clinical trials evaluating initial treatment of cGVHD in resource-constrained locations.
Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estados Unidos , Humanos , Brasil/epidemiología , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Injerto contra Huésped/tratamiento farmacológicoRESUMEN
The survival rates of children with high-risk acute myeloid leukemia (AML) treated with hematopoietic stem cell transplant (HSCT) range from 60% to 70% in high-income countries. The corresponding rate for Brazilian children with AML who undergo HSCT is unknown. We conducted a retrospective analysis of 114 children with AML who underwent HSCT between 2008 and 2012 at institutions participating in the Brazilian Pediatric Bone Marrow Transplant Working Group. At transplant, 38% of the children were in first complete remission (CR1), 37% were in CR2, and 25% were in CR3+ or had persistent disease. The donors included 49 matched-related, 59 matched-unrelated, and six haploidentical donors. The most frequent source of cells was bone marrow (69%), followed by the umbilical cord (19%) and peripheral blood (12%). The 4-year overall survival was 47% (95% confidence interval [CI] 30%-57%), and the 4-year progression-free survival was 40% (95% CI 30%-49%). Relapse occurred in 49 patients, at a median of 122 days after HSCT. There were 65 deaths: 40 related to AML, 19 to infection, and six to graft versus host disease. In conclusion, our study suggests that HSCT outcomes for children with AML in CR1 or CR2 are acceptable and that this should be considered in the overall treatment planning for children with AML in Brazil. Therapeutic standardization through the adoption of multicentric protocols and appropriate supportive care treatment will have a significant impact on the results of HSCT for AML in Brazil and possibly in other countries with limited resources.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Adolescente , Brasil , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Células Madre Hematopoyéticas/citología , Humanos , Lactante , Leucemia Mieloide Aguda/microbiología , Leucemia Mieloide Aguda/virología , Masculino , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto JovenRESUMEN
The Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease was approved by Sociedade Brasileira de Transplante de Medula Óssea , with the participation of 26 Brazilian hematopoietic stem cell transplantation centers. It describes the main nutritional protocols in cases of Graft- versus -host disease, the main complication of hematopoietic stem cell transplantation.
Asunto(s)
Conferencias de Consenso como Asunto , Enfermedad Injerto contra Huésped/dietoterapia , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia Nutricional/normas , Necesidades Nutricionales , Brasil , Congresos como Asunto , Enfermedades Gastrointestinales/dietoterapia , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/fisiopatología , Enfermedad Injerto contra Huésped/fisiopatología , Humanos , Terapia Nutricional/métodos , Índice de Severidad de la EnfermedadAsunto(s)
Citometría de Flujo , Leucemia Mieloide Aguda , Neoplasia Residual , Humanos , Neoplasia Residual/diagnóstico , Citometría de Flujo/métodos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Femenino , Masculino , Anciano , AdultoRESUMEN
Hematopoietic stem cell transplant (HSCT) recipients should be routinely revaccinated after transplantation. We evaluated the difficulties met in the revaccination program and how a prospective and tailored follow-up could help to overcome these obstacles. HSCT recipients (n=122) were prospectively followed up and categorized into Group 1 (n=72), recipients who had already started the revaccination program, and Group 2 (n=50), recipients starting their vaccines. Whenever a difficulty was reported, interventions and subsequent evaluations were performed. Reported problems were related to patient compliance, HSCT center and/or vaccination center. Problems related to patient compliance were less frequent than those related to HSCT center modifications of previous recommendations, or to errors made by the vaccination center. The main gap found was vaccination delays (81.9%). Advisory intervention was needed in 64% and 46% of Group 1 and Group 2, respectively (p=0.05), and was partially successful in around 70% of the cases. Total resolution was achieved in more than 35% in both groups. Improvements are needed in the Brazilian vaccination program for HSCT recipients to assure a complete and updated revaccination schedule. HSCT centers should assign nurses and transplant infectious disease specialist physicians to organize the revaccination schedule and to monitor the program development.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Esquemas de Inmunización , Inmunización Secundaria , Adolescente , Adulto , Anciano , Vacunas Bacterianas/administración & dosificación , Brasil , Niño , Preescolar , Femenino , Humanos , Inmunización Secundaria/estadística & datos numéricos , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Vacunas Virales/administración & dosificación , Adulto JovenRESUMEN
ABSTRACT The Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease was approved by Sociedade Brasileira de Transplante de Medula Óssea , with the participation of 26 Brazilian hematopoietic stem cell transplantation centers. It describes the main nutritional protocols in cases of Graft- versus -host disease, the main complication of hematopoietic stem cell transplantation.
RESUMO O Consenso Brasileiro de Nutrição no Transplante de Células Tronco Hematopoiéticas: doença do enxerto contra o hospedeiro foi aprovado pela Sociedade Brasileira de Transplante de Medula Óssea, com a participação de 26 centros brasileiros de transplante de células-tronco hematopoiéticas. O Consenso descreve as principais condutas nutricionais em casos de doença do enxerto contra o hospedeiro, a principal complicação do transplante de células-tronco hematopoiéticas.
Asunto(s)
Conferencias de Consenso como Asunto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia Nutricional/normas , Enfermedad Injerto contra Huésped/dietoterapia , Enfermedad Injerto contra Huésped/etiología , Necesidades Nutricionales , Índice de Severidad de la Enfermedad , Brasil , Congresos como Asunto , Terapia Nutricional/métodos , Enfermedades Gastrointestinales/dietoterapia , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/fisiopatología , Enfermedad Injerto contra Huésped/fisiopatologíaRESUMEN
O transplante de células-tronco hematopoéticas (TCTH) é o tratamento de escolha para leucemias agudas de alto risco. Apesar da melhora na sobrevida destes pacientes, a recidiva continua sendo a maior causa de óbito pós-transplante de células-tronco hematopoéticas. O objetivo deste trabalho foi analisar os resultados dos transplantes realizados em crianças com leucemia aguda em duas instituições brasileiras. Realizou-se estudo retrospectivo de 208 pacientes transplantados entre 1990-2007. Mediana de idade: 9 anos; 119 pacientes com leucemia linfoide aguda (LLA) e 89 com leucemia mieloide aguda (LMA). Doença precoce: CR1 e CR2. ... 14/195 pacientes tiveram falha primária de pega (8 por cento). Não houve diferença na sobrevida global e sobrevida livre de recaída entre pacientes com leucemia linfoide aguda e leucemia mieloide aguda, entre transplantes aparentados e não aparentados, tampouco entre as fontes de células utilizadas. O desenvolvimento da doença do enxerto contra hospedeiro (DECH) aguda ou crônica também não influenciou a sobrevida global e sobrevida livre de recaída. Pacientes com leucemia linfoide aguda condicionados com irradiação corporal total (TBI) apresentaram melhor sobrevida global e sobrevida livre de recaída (p<0,001). Cento e dezoito pacientes morreram entre 1-1.654 dias pós-transplante de células-tronco hematopoéticas (M:160). Mortalidade relacionada a transplante (MRT) (dia+100): 16 por cento. Incidência cumulativa de recaída: 40 por cento (3 anos). Pacientes com doença avançada tiveram menor sobrevida global e sobrevida livre de recaída (três anos)(p<0,001). Na análise multivariada, o status da doença foi o principal fator associado ao aumento da sobrevida global e sobrevida livre de recaída. Nossos resultados mostram que é possível se atingir uma boa sobrevida para pacientes com doença precoce e também mostram a baixa eficácia naqueles com doença avançada.
Hematopoietic Stem Cell transplantation (HSCT) is the treatment of choice for patients with high-risk leukemia. In spite of this, relapse remains a major cause of death of these patients. Our objective was to analyze the outcomes of patients with acute leukemia submitted to hematopoietic stem cell transplantation in two Brazilian institutions... There were no differences in the overall survival and event free survival between patients with acute lymphocytic leukemia and acute myeloid leukemia, between sources of cells used or between those who developed acute or chronic graft-versus-host disease (GVHD). When comparing transplants from related and unrelated donors, there was no difference in the overall survival. Patients with acute lymphocytic leukemia receiving the total body irradiation (TBI) conditioning regimen had better overall survival and event free survival (p<0.001). One hundred and eighteen patients died between 0 and 1654 days after hematopoietic stem cell transplantation (M: 160 days). Transplantation-related-mortality (TRM) at D+100 was 16 percent and cumulative incidence of relapse was 40 percent (3 years). Patients with advanced disease had lower 3-year overall survival and event free survival (p<0.001). Multivariate analysis showed that disease status was the most significant factor associated with higher event free survival and overall survival . Our results show that children and adolescents transplanted with early disease can achieve considerable overall survival and also highlights the inefficacy of hematopoietic stem cell transplantation for patients with advanced disease.