RESUMEN
BACKGROUND: There is a lack of studies analyzing the association between oral mucositis (OM) and nutritional imbalance in children during hematopoietic stem cell transplantation (HSCT). The aim of this study was to compare the risk factors for OM and nutritional imbalance during HSCT in pediatric patients with nonmalignant diseases (NMD) and malignant diseases (MD). METHODS: Data on age, sex, primary disease, transplantation type, conditioning regimen, GVHD prophylaxis, gastrointestinal toxicity, OM, percent body weight loss or gain, nutritional repositioning, and overall survival (OS) were retrospectively collected from the 132 medical records. The data were then compared between patients with NMD (n = 70) and MD (n = 62). RESULTS: OM had a similar severity between the groups. The primary risk factor for OM in the NMD group was the conditioning regimen with busulfan, while in the MD group it was GVHD prophylaxis with cyclosporin and methotrexate. OM did not have an impact on body weight loss or gain in any of the groups. In the NMD, body weight gain due to fluid overload was more pronounced and associated with a lower age range. OS was similar between the groups and was not affected by OM. CONCLUSIONS: OM pattern was similar in pediatric patients with or without MD, but the factors that determined these oral lesions were different. There were disparities in body weight changes between the two groups, and these changes were not associated to OM.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estado Nutricional , Estomatitis , Acondicionamiento Pretrasplante , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Femenino , Masculino , Niño , Preescolar , Estomatitis/etiología , Estudios Retrospectivos , Adolescente , Lactante , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/efectos adversos , Factores de Riesgo , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias/complicacionesRESUMEN
PURPOSE: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection. METHODS: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. RESULTS: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. CONCLUSION: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).
Asunto(s)
COVID-19/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , SARS-CoV-2/fisiología , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Adulto , Enfermedades Asintomáticas , Brasil , COVID-19/mortalidad , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de Inmunodeficiencia Primaria/mortalidad , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Síndrome de Respuesta Inflamatoria Sistémica/mortalidad , Adulto JovenRESUMEN
Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/µL CD4+ and 1000/µL CD3+ cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedades de Inmunodeficiencia Primaria , Niño , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Lactante , Masculino , Acondicionamiento PretrasplanteRESUMEN
Severe aplastic anemia (SAA) is a life-threatening disease that can be cured with allogeneic cell transplantation (HCT). Haploidentical donor transplantation with post-transplantation cyclophosphamide (haplo-PTCy) is an option for patients lacking an HLA-matched donor. We analyzed 87 patients who underwent haplo-PTCy between 2010 and 2019. The median patient age was 14 years (range, 1 to 69 years), most were heavily transfused, and all received previous immunosuppression (25% without antithymocyte globulin). Almost two-thirds (63%) received standard fludarabine (Flu)/cyclophosphamide (Cy) 29/total body irradiation (TBI) 200 cGy conditioning, and the remaining patients received an augmented conditioning: Flu/Cy29/TBI 300-400 (16%), Flu/Cy50/TBI 200 (10%), or Flu/Cy50/TBI 400 (10%). All patients received PTCy-based graft-versus-host disease (GVHD) prophylaxis. Most grafts (93%) were bone marrow (BM). The median duration of follow-up was 2 years and 2 months. The median time to neutrophil recovery was 17 days. Primary graft failure occurred in 15% of the patients, and secondary or poor graft function occurred in 5%. The incidences of grade II-IV acute GVHD was 14%, and that of chronic GVHD was 9%. Two-year overall survival and event-free survival (EFS) were 79% and 70%, respectively. EFS was higher for patients who received augmented Flu/Cy/TBI (hazard ratio [HR], .28; P = .02), and those who received higher BM CD34 cell doses (>3.2 × 10E6/kg) (HR, .29; P = .004). The presence of donor-specific antibodies before HSCT was associated with lower EFS (HR, 3.92; P = .01). Graft failure (HR, 7.20; P < .0001) was associated with an elevated risk of death. Cytomegalovirus reactivation was frequent (62%). Haploidentical HCT for SAA is a feasible procedure; outcomes are improved with augmented conditioning regimens and BM grafts with higher CD34 cell doses.
Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Anemia Aplásica/terapia , Niño , Preescolar , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Lactante , Persona de Mediana Edad , Acondicionamiento Pretrasplante , Adulto JovenRESUMEN
Busulfan is given in the conditioning regimens preceding hematopoietic stem cell transplantation (HSCT), and plasma levels can be monitored. A targeted, individualized systemic exposure (SE) dose can be achieved by calculating the area under the plasma concentration versus time curve (AUC). The objective of this study was to determine a cutoff value for safety for the AUC for busulfan plasma levels in patients undergoing HSCT. A total of 149 consecutive HSCT patients were studied. After an oral test dose of busulfan, we set target doses of 4000, 5000, or 6000 µMol⸱min/day, and analyzed the AUC of oral or intravenous Bu. These patients were compared with 53 historical control subjects who had received myeloablative conditioning regimen without busulfan pharmacokinetic monitoring. Using a test dose and the administration route had no impact on the sinusoidal obstructive syndrome (SOS) incidence, transplant-related mortality or 1-year overall survival. However, patients receiving busulfan at doses set up at AUC > 5000 had an increased risk to develop SOS after HSCT (hazard ratio 3.39, p = 0.034, 95% CI 1.09-10.52). Adjusting the busulfan dose according to SE levels target dose during conditioning is associated with lower rates of oral severe mucositis and SOS. A cutoff of 5000 µMol⸱min is safe and does not impair survival.
Asunto(s)
Busulfano/administración & dosificación , Busulfano/efectos adversos , Enfermedad Veno-Oclusiva Hepática/etiología , Acondicionamiento Pretrasplante/efectos adversos , Administración Intravenosa , Administración Oral , Adolescente , Área Bajo la Curva , Busulfano/farmacocinética , Niño , Preescolar , Ensayos Clínicos Controlados como Asunto , Susceptibilidad a Enfermedades , Femenino , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Enfermedad Veno-Oclusiva Hepática/epidemiología , Enfermedad Veno-Oclusiva Hepática/mortalidad , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Pronóstico , Acondicionamiento Pretrasplante/métodos , Adulto JovenRESUMEN
The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 107 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/terapia , Brasil/epidemiología , Niño , Femenino , Supervivencia de Injerto , Humanos , Incidencia , Leucemia Mieloide Aguda/epidemiología , Masculino , Síndromes Mielodisplásicos/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Severe combined immunodeficiency (SCID) represents the most lethal form of primary immunodeficiency, with mortality rates of greater than 90% within the first year of life without treatment. Hematopoietic stem cell transplantation and gene therapy are the only curative treatments available, and the best-known prognostic factors for success are age at diagnosis, age at hematopoietic stem cell transplantation, and the comorbidities that develop in between. There are no evidence-based guidelines for standardized clinical care for patients with SCID during the time between diagnosis and definitive treatment, and we aim to generate a consensus management strategy on the supportive care of patients with SCID. First, we gathered available information about SCID diagnostic and therapeutic guidelines, then we developed a document including diagnostic and therapeutic interventions, and finally we submitted the interventions for expert consensus through a modified Delphi technique. Interventions are grouped in 10 topic domains, including 123 "agreed" and 38 "nonagreed" statements. This document intends to standardize supportive clinical care of patients with SCID from diagnosis to definitive treatment, reduce disease burden, and ultimately improve prognosis, particularly in countries where newborn screening for SCID is not universally available and delayed diagnosis is the rule. Our work intends to provide a tool not only for immunologists but also for primary care physicians and other specialists involved in the care of patients with SCID.
Asunto(s)
Guías de Práctica Clínica como Asunto , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/terapia , Consenso , Humanos , América LatinaRESUMEN
In this study, we report on major MRD or URD BMT outcomes in pediatric patients with SAA in Brazil. This was a retrospective study, which included 106 patients ≤18 years old who received a first BMT for SAA. All patients received bone marrow as graft source from an MRD (n = 69) or a URD (n = 37). Conditioning regimen was non-myeloablative in 73.6% of cases, and GVHD prophylaxis comprised a calcineurin inhibitor plus methotrexate in 89.6% of patients. After a median follow-up of 4.5 years after BMT, 81 patients are alive, with a 4-year OS of 77% and no statistically significant difference between the MRD and URD groups (82% vs. 69%, respectively; P = .08). Grade III-IV aGVHD at 6 months and cGVHD at 2 years were observed in 8% and 14% of cases, respectively, and were not statistically different between the groups. Twenty-five (23%) patients died at a median of 2.9 months after BMT. Our study showed that 4-year OS after BMT was not statistically different between MRD and URD recipients. This study shows that the outcomes of pediatric patients transplanted for SAA with a URD in Brazil are approaching those of MRD transplants. In contrast, OS after MRD BMT was lower than we would expect based on previous reports. The wide range of preparatory regimens used by the study centers highlights the need for standardized protocols for these children. Our findings provide a benchmark for future studies focused on improving BMT outcomes in this setting in Brazil.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Médula Ósea/métodos , Donante no Emparentado , Adolescente , Brasil , Niño , Preescolar , Países en Desarrollo , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Cooperación Internacional , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trasplante Homólogo , Resultado del Tratamiento , WashingtónRESUMEN
BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.
Asunto(s)
Diabetes Mellitus Tipo 1/congénito , Diarrea , Factores de Transcripción Forkhead , Enfermedades Genéticas Ligadas al Cromosoma X , Trasplante de Células Madre Hematopoyéticas , Enfermedades del Sistema Inmune/congénito , Terapia de Inmunosupresión , Mutación , Adolescente , Adulto , Aloinjertos , Niño , Preescolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/mortalidad , Diabetes Mellitus Tipo 1/terapia , Diarrea/genética , Diarrea/inmunología , Diarrea/mortalidad , Diarrea/terapia , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/mortalidad , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Humanos , Enfermedades del Sistema Inmune/genética , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/mortalidad , Enfermedades del Sistema Inmune/terapia , Lactante , Masculino , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.
Asunto(s)
Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas , Síndromes de Inmunodeficiencia/terapia , Enfermedades Raras/terapia , Brasil/epidemiología , Diagnóstico Tardío , Países en Desarrollo , Femenino , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Síndromes de Inmunodeficiencia/epidemiología , Síndromes de Inmunodeficiencia/mortalidad , Lactante , Recién Nacido , Masculino , Tamizaje Neonatal , Enfermedades Raras/epidemiología , Enfermedades Raras/mortalidad , Análisis de SupervivenciaRESUMEN
OM is a painful inflammatory condition of the oral mucosa, derived from the toxic effects of chemotherapy and radiotherapy. High OM severity is frequently present in HSCT pediatric patients, who exhibit multiple painful ulcers that limit their mastication and swallowing, leading to poor nutritional status. Few studies have demonstrated OM clinical outcomes in young patients undergoing HSCT. Feasibility of oral care and LLLT on OM prophylaxis and treatment is also poorly discussed. The aim of this study was to describe a specialized oral care protocol that included LLLT for pediatric patients undergoing transplantation and to demonstrate the clinical outcomes after OM prevention and treatment. Data from OM-related morbidity were collected from 51 HSCT pediatric patients treated daily with LLLT, followed by standard oral care protocols. All the patients, even infants and young children, accepted the daily oral care and LLLT well. The majority (80.0%) only exhibited erythema in the oral mucosa, and the maximum OM degree was WHO II. Patients who had undergone autologous and HLA-haploidentical transplants showed OM with the lowest severity. The frequency of total body irradiation and methotrexate prescriptions was higher in adolescents when compared with infants (p = 0.044), and adolescents also exhibited OM more severely than infants and young children. We found that good clinical outcomes were obtained using this therapy, mainly in regard to the control of OM severity and pain reduction in the oral cavity. Specialized oral care, including LLLT, is feasible and affordable for HSCT pediatric patients, although some adaptation in the patient's oral hygiene routine must be adopted with help from parents/companions and clinical staff.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia por Láser/métodos , Rayos Láser , Terapia por Luz de Baja Intensidad/métodos , Estomatitis/diagnóstico , Estomatitis/etiología , Administración Oral , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Inflamación , Masculino , Higiene Bucal , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
BACKGROUND: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). METHODS: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. RESULTS: The median (range) age was 12.5 (0.3-65) years and the mean ± SD dose (×106/kg) was 4.73 ± 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). CONCLUSIONS: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable.
RESUMEN
Objective: To describe the radiological findings in pediatric patients with hematological or oncological diseases who also have an invasive fungal infection (IFI). Materials and Methods: This was a retrospective study of all patients with IFI admitted to a pediatric hematology and oncology hospital in Brazil between 2008 and 2014. Clinical and demographic data were collected. Chest computed tomography (CT) scans of the patients were reviewed by two independent radiologists. Results: We evaluated the chest CT scans of 40 pediatric patients diagnosed with an IFI. Twenty-seven patients (67.5%) had nodules with the halo sign, seven (17.5%) had cavities, two (5.0%) had nodules without the halo sign, and seven (17.5%) had consolidation. The patients with the halo sign and cavities were older (123 vs. 77 months of age; p = 0.03) and had less severe disease (34% vs. 73%; p = 0.04). Ten patients had a proven IFI: with Aspergillus sp. (n = 4); with Candida sp. (n = 5); or with Fusarium sp. (n = 1). Conclusion: A diagnosis of IFI should be considered in children and adolescents with risk factors and abnormal CT scans, even if the imaging findings are nonspecific.
Objetivo: O objetivo deste estudo é descrever os achados radiológicos de infecções fúngicas invasivas em crianças com doenças onco-hematológicas em um único centro, de acordo com a classificação antiga e a atual de imagens típicas e atípicas. Materiais e Métodos: Foram revisados os prontuários de todos os pacientes com infecção fúngica invasiva que foram internados em um hospital pediátrico de oncologia e hematologia de 2008 a 2014. Foram coletados dados clínicos e demográficos. As tomografias de tórax dos pacientes foram laudadas por dois radiologistas independentes. Resultados: Foram identificados 40 pacientes com infecção fúngica invasiva que realizaram tomografias de tórax. Vinte e sete pacientes apresentaram nódulos com sinal do halo (67,5%), sete tiveram cavitações (17,5%), dois tiveram nódulos sem halo (5,0%) e sete apresentaram consolidações (17,5%). Os pacientes que apresentavam achados de nódulos com sinal do halo e cavitações eram mais velhos (123 versus 77 meses; p = 0,03) e tinham menos sinais de doença grave (34% versus 73%; p = 0,04) do que os outros pacientes. Dez crianças apresentaram infecção confirmada (Aspergillus sp., n = 4; Candida sp., n = 5; Fusarium sp., n = 1). Conclusão: O diagnóstico de infecção fúngica invasiva deve ser considerado em crianças com fatores de risco e tomografias de tórax alteradas, mesmo que os achados das imagens sejam inespecíficos.
RESUMEN
In the COVID-19 scenario, patients undergoing hematopoietic stem cell transplantation (HSCT) infected with SARS-CoV-2 may have an increased risk of death. Through a national multicenter study, we aimed to describe the impact of COVID-19 on the survival of HSCT recipients in Brazil. Eighty-six patients with a confirmed diagnosis of SARS-CoV-2 (92% by RT-PCR) were included. There were 24 children and 62 adults receiving an autologous (n = 25) and allogeneic (n = 61) HSCT for malignant (n = 72) and non-malignant (n = 14) disorders. Twenty-six patients died, (10 on autologous (38%) and 16 patients (62%) on allogeneic group). The estimated overall survival (OS) at day 40 was 69%. Adults had decreased OS compared to children (66% vs 79%, p = 0.03). The severity of symptoms at the time of diagnosis, ECOG score, laboratory tests (C-reactive protein, urea values) were higher in patients who died (p < 0.05). In conclusion, HSCT recipients infected with SARS-CoV-2 have a high mortality rate mainly in adults and patients with critical initial COVID-19 presentation. These findings show the fragility of HSCT recipients with SARS-CoV-2 infection. Therefore, the importance of adherence to preventive measures is evident, in addition to prioritizing the vaccination of family members and the HSCT team.
Asunto(s)
COVID-19 , Trasplante de Células Madre Hematopoyéticas , Adulto , Brasil/epidemiología , COVID-19/complicaciones , Niño , Humanos , SARS-CoV-2 , Tasa de SupervivenciaRESUMEN
Chimeric antigen receptor T (CAR-T) cell therapy is a novel therapeutic modality for acute lymphoblastic leukemia (ALL) with robust outcomes in patients with refractory or relapsed disease. At the same time, CAR-T cell therapy is associated with unique and potentially fatal toxicities, such as cytokine release syndrome (CRS) and neurological toxicities (ICANS). This manuscript aims to provide a consensus of specialists in the fields of Hematology Oncology and Cellular Therapy to make recommendations on the current scenario of the use of CAR-T cells in patients with ALL.
RESUMEN
The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian Society of Bone Marrow Transplantation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Adolescente , Brasil , Niño , Consenso , Humanos , Evaluación Nutricional , Estado NutricionalRESUMEN
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
Busulfan is used in myeloablative schemes for hematopoietic stem cell transplantation (HSCT), with monitoring of dosage through the area under the curve (AUC) of the drug plasma concentration (µMol min). In this study, we compared the complete pharmacokinetics of busulfan administered orally (Bu-Oral) and intravenously (Bu-IV). We evaluated 40 patients who underwent HSCT with different types of conditioning regimens. After one dose, in the Bu-Oral group (n = 21), the median AUC was 1174 µMol min (799-4000), reaching a median of 4440 µMol min (3428-7181.5) during conditioning in 24 h. In the Bu-IV group (n = 19), it was 1244.8 µMol min (1001.2-2021), reaching 5598.0 µMol min (3102-8818) during conditioning in 24 h. Measuring plasma concentration of Bu in patients undergoing HSCT is important, regardless of the formulation, and the inclusion of a pre-HSCT test can predict the optimal dose during conditioning. Pharmacokinetics of the oral administration of busulfan, as well as clearance, are extremely variable, and this can potentially compromise the clinical results of the treatment since it makes it difficult to predict clinical results.
Asunto(s)
Busulfano , Trasplante de Células Madre Hematopoyéticas , Mucositis , Administración Intravenosa , Administración Oral , Adolescente , Adulto , Anciano , Busulfano/administración & dosificación , Busulfano/farmacocinética , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucositis/sangre , Mucositis/prevención & controlRESUMEN
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources. We describe the outcomes of transplants performed for nine X-ALD patients using haploidentical donors and PT/Cy. Patients received conditioning regimen with fludarabine 150 mg/m2, cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and mycophenolate mofetil. One patient had a primary graft failure and was not eligible for a second transplant. Three patients had secondary graft failure and were successfully rescued with second haploidentical transplants. Trying to improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for 4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17-37 months after transplant). Haploidentical HSCT with PT/Cy is a feasible alternative for X-ALD patients lacking a suitable matched donor. Graft failure has to be addressed in further studies.
Asunto(s)
Adrenoleucodistrofia/terapia , Trasplante de Médula Ósea/métodos , Ciclofosfamida/uso terapéutico , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Niño , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Humanos , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Abstract Objective: To describe the radiological findings in pediatric patients with hematological or oncological diseases who also have an invasive fungal infection (IFI). Materials and Methods: This was a retrospective study of all patients with IFI admitted to a pediatric hematology and oncology hospital in Brazil between 2008 and 2014. Clinical and demographic data were collected. Chest computed tomography (CT) scans of the patients were reviewed by two independent radiologists. Results: We evaluated the chest CT scans of 40 pediatric patients diagnosed with an IFI. Twenty-seven patients (67.5%) had nodules with the halo sign, seven (17.5%) had cavities, two (5.0%) had nodules without the halo sign, and seven (17.5%) had consolidation. The patients with the halo sign and cavities were older (123 vs. 77 months of age; p = 0.03) and had less severe disease (34% vs. 73%; p = 0.04). Ten patients had a proven IFI: with Aspergillus sp. (n = 4); with Candida sp. (n = 5); or with Fusarium sp. (n = 1). Conclusion: A diagnosis of IFI should be considered in children and adolescents with risk factors and abnormal CT scans, even if the imaging findings are nonspecific.
Resumo Objetivo: O objetivo deste estudo é descrever os achados radiológicos de infecções fúngicas invasivas em crianças com doenças onco-hematológicas em um único centro, de acordo com a classificação antiga e a atual de imagens típicas e atípicas. Materiais e Métodos: Foram revisados os prontuários de todos os pacientes com infecção fúngica invasiva que foram internados em um hospital pediátrico de oncologia e hematologia de 2008 a 2014. Foram coletados dados clínicos e demográficos. As tomografias de tórax dos pacientes foram laudadas por dois radiologistas independentes. Resultados: Foram identificados 40 pacientes com infecção fúngica invasiva que realizaram tomografias de tórax. Vinte e sete pacientes apresentaram nódulos com sinal do halo (67,5%), sete tiveram cavitações (17,5%), dois tiveram nódulos sem halo (5,0%) e sete apresentaram consolidações (17,5%). Os pacientes que apresentavam achados de nódulos com sinal do halo e cavitações eram mais velhos (123 versus 77 meses; p = 0,03) e tinham menos sinais de doença grave (34% versus 73%; p = 0,04) do que os outros pacientes. Dez crianças apresentaram infecção confirmada (Aspergillus sp., n = 4; Candida sp., n = 5; Fusarium sp., n = 1). Conclusão: O diagnóstico de infecção fúngica invasiva deve ser considerado em crianças com fatores de risco e tomografias de tórax alteradas, mesmo que os achados das imagens sejam inespecíficos.