Low rate of nonrelapse mortality in under-4-year-olds with ALL given chemotherapeutic conditioning for HSCT: a phase 3 FORUM study.

ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged <4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: <0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade >1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129.

COVID-19 in Pediatric Cancer Patients and Hematopoietic Stem Cell Transplant Recipients in a Tertiary Care Hospital in Argentina.

The outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer pediatric patients was initially uncertain. The objective of this study was to describe the characteristics and outcome of cancer patients and hematopoietic stem cell transplant recipients from 0 to 19 years with detectable SARS-CoV-2 from April 23, 2020, to April 30, 2022, treated in a tertiary-level hospital in Argentina. A total of 348 cases were registered in 339 patients. The median age was 89.5 (3 to 224) months. The sex was predominantly male: 193 (55.5%). The most common malignant disease was leukemia (42.8%). One hundred four cases (29.9%) had comorbidities. Of the 346 cases with an available blood count, 17.6% had a lymphocyte count <300/mm 3 . Fever was the most common symptom. In most cases (93.1%) presented asymptomatic or mild disease. Twenty-one cases (6%) presented severe or critical status. Eleven of 24 admissions to the intensive care unit were due to COVID-19 (coronavirus disease 2019). Eight patients (2.3%) died. Two deaths were attributable to SARS-CoV-2 (0.6%). Being older, having fever, lymphopenia at diagnosis, and having received hematopoietic stem cell transplant were associated with a more severe disease. Around 90% of the children continued their cancer treatment without any change.

Algunos desafíos en mucopolisacaridosis tipo I / A few challenges in mucopolysaccharidosis type I

Se describen como desafíos actuales en mucopolisacaridosis I la necesidad de una clasificación adecuada, vinculándola a las indicaciones terapéuticas; el diagnóstico temprano desde la pesquisa neonatal, sus ventajas y dificultades hasta la sospecha clínica de las formas grave y atenuada; el cuidado de la patología espinal y oftalmológica, desde el diagnóstico, el seguimiento y el tratamiento; las reacciones alérgicas por terapia de reemplazo enzimático, su diagnóstico y tratamiento. Por último, la transición hacia el cuidado adulto

Here we describe the current challenges of mucopolysaccharidosis type I: the need for an adequate classification, establishing its relationship to therapeutic indications; an early diagnosis, from neonatal screening, its advantages and barriers, to clinical suspicion of severe and attenuated forms; spinal and eye disease care, from diagnosis to follow-up and treatment; allergic reactions caused by enzyme replacement therapy, their diagnosis and treatment. And lastly, transition to adult care

A few challenges in mucopolysaccharidosis type I. / Algunos desafíos en mucopolisacaridosis tipo I.

Here we describe the current challenges of mucopolysaccharidosis type I: the need for an adequate classification, establishing its relationship to therapeutic indications; an early diagnosis, from neonatal screening, its advantages and barriers, to clinical suspicion of severe and attenuated forms; spinal and eye disease care, from diagnosis to follow-up and treatment; allergic reactions caused by enzyme replacement therapy, their diagnosis and treatment. And lastly, transition to adult care.

Se describen como desafíos actuales en mucopolisacaridosis I la necesidad de una clasificación adecuada, vinculándola a las indicaciones terapéuticas; el diagnóstico temprano desde la pesquisa neonatal, sus ventajas y dificultades hasta la sospecha clínica de las formas grave y atenuada; el cuidado de la patología espinal y oftalmológica, desde el diagnóstico, el seguimiento y el tratamiento; las reacciones alérgicas por terapia de reemplazo enzimático, su diagnóstico y tratamiento. Por último, la transición hacia el cuidado adulto.

Nuevas recomendaciones para el cuidado de los pacientes con mucopolisacaridosis tipo I / New recommendations for the care of patients with mucopolysaccharidosis type I

Dados los avances sobre mucopolisacaridosis Icon posterioridad al consenso publicado en la Argentina por un grupo de expertos en 2008, se revisan recomendaciones respecto a estudios genéticos, seguimiento cardiológico, cuidado de la vía aérea, alertas sobre aspectos auditivos, de la patología espinal y neurológica. Se hace revisión de la terapéutica actual y se enfatiza en la necesidad de un diagnóstico y tratamiento precoces, así como de un seguimiento interdisciplinario

Considering the advances made on mucopolysaccharidosis type I after the consensus study published by a group of experts in Argentina in 2008, recommendations about genetic testing, cardiological follow-up, airway care, hearing impairment detection, spinal and neurological conditions, as well as current treatments, were reviewed. Emphasis was placed on the need for early diagnosis and treatment, as well as an interdisciplinary follow-up

New recommendations for the care of patients with mucopolysaccharidosis type I. / Nuevas recomendaciones para el cuidado de los pacientes con mucopolisacaridosis tipo I.

Considering the advances made on mucopolysaccharidosis type I after the consensus study published by a group of experts in Argentina in 2008, recommendations about genetic testing, cardiological follow-up, airway care, hearing impairment detection, spinal and neurological conditions, as well as current treatments, were reviewed. Emphasis was placed on the need for early diagnosis and treatment, as well as an interdisciplinary follow-up.

Dados los avances sobre mucopolisacaridosis I con posterioridad al consenso publicado en la Argentina por un grupo de expertos en 2008, se revisan recomendaciones respecto a estudios genéticos, seguimiento cardiológico, cuidado de la vía aérea, alertas sobre aspectos auditivos, de la patología espinal y neurológica. Se hace revisión de la terapéutica actual y se enfatiza en la necesidad de un diagnóstico y tratamiento precoces, así como de un seguimiento interdisciplinario.

Intensive Safety Monitoring of Rituximab (Biosimilar Novex® and the Innovator) in Pediatric Patients With Complex Diseases.

Although rituximab is widely used off-label for complex pediatric diseases, safety reports are limited. We aimed to report evidence of its use in clinical practice, to describe the incidence of adverse drug reactions (ADR) to rituximab biosimilar Novex® and innovator, and to identify risk factors for the development of ADR in a real-life follow-up cohort of pediatric patients with complex diseases. We conducted a prospective, longitudinal, observational, single-centre study in patients that received rituximab for any complex disease, and as part of an intensive pharmacovigilance program. Demographic, pharmacological, clinical, and drug-related data were collected for all patients. ADR-free survival, including infusion-related reactions (IRR) and delayed ADR (dADR), was estimated using Kaplan-Meier curves. Risk factors were evaluated by multivariable Cox regression models. In total, 77 patients (<19 y.o.) received 187 infusions of rituximab Novex® (n = 155) or innovator rituximab (n = 32) for neurologic (Neu), immune-hematologic-rheumatic (IHR), oncologic (O) diseases, and hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation (SOT). We recorded 29 IRR and 58 dADR that occurred in 27 (35.1%) and 29 (37.7%) patients, respectively. The respiratory tract was the most affected during IRR (29.6%) and hypogammaglobulinemia (37.9 %) was the most frequent dADR. First versus subsequent infusions (HR 5.4, CI95% 2.4-12.1, p<0.05), sex (boys vs. girls, HR 0.3, CI95% 0.1-0.8, and p<0.05), and diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 2.3, CI95% 1.02-5.4, and p < 0.05) were significantly associated with the development of IRR. For dADR, risk factors were diagnosis (Neu-IHR diseases vs. O-HSCT-SOT, HR 0.4, CI95% 0.2-0.9, and p < 0.05) and cumulative body surface area-normalized dosage (HR 1.0003, CI95% 1.0001-1.0006, and p < 0.05). The present is the largest real-world safety assessment of rituximab in Latin-American children with complex diseases supporting its use based on the overall acceptable safety. Identification of risk factors may contribute to optimization of off-label rituximab treatment in pediatrics.

Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study.

PURPOSE: Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients. PATIENTS AND METHODS: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129). RESULTS: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively. CONCLUSION: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.

Estado de situación del proceso de transición-transferencia de adolescentes con enfermedades crónicas en un hospital pediátrico de referencia nacional en Argentina / Status of the transition/transfer process for adolescents with chronic diseases at a national pediatric referral hospital in Argentina

Introducción: El pasaje de adolescentes de un centro pediátrico a otro de adultos es un proceso complejo. El objetivo fue evaluar el proceso de transición-transferencia de adolescentes con enfermedades crónicas en el Hospital Garrahan. Métodos: Estudio observacional, transversal, cualicuantitativo. Se obtuvieron datos estadísticos retrospectivos sobre la consulta ambulatoria de pacientes de 16-26 años y se realizaron encuestas y/o entrevistas a profesionales, adolescentes y familiares de diferentes programas de seguimiento. Resultados: La prevalencia de atención a mayores de 16 años fue 7, 2%. Se encuestaron 54 profesionales asistentes, 150 pacientes (1626, 7 años) y 141 familiares. Se entrevistó a 45 profesionales con cargos de gestión. Profesionales: el 39% recibió capacitación en transición. Todos identificaron obstáculos y facilitadores en los diferentes actores e instituciones intervinientes. Reconocieron la importancia en fomentar la autonomía en sus pacientes, pero solo 30% los entrevistaba solos y 56, 6% les entregaba informes médicos. Estrategias: la mediana de edad de transferencia fue18 años (13-20); 62% tenía un protocolo; 84%, un acuerdo informal con otra institución; atención conjunta o paralela: 49%;solo 20% utilizaba un plan de transición. Pacientes y familiares: 4, 7% de los adolescentes concurrían solos a las consultas y el profesional le había preguntado al 45% sobre su autonomía y preparación para cuidar su salud. Los adolescentes y sus padres percibían sensaciones asociadas al proceso (con predominio, negativas) e identificaban estrategias facilitadoras, como contar con un resumen, conocer el nuevo lugar y profesionales formados. Conclusiones: El proceso de transición del adolescente con enfermedad crónica es aún deficitario y su abordaje incluye a los equipos de salud y a las familias. Se identificaron falta de acuerdos interinstitucionales formales, aunque sí mayores acuerdos informales entre los profesionales, y la necesidad de fomentar la autonomía del paciente crónico. Entre las estrategias facilitadoras, los pacientes y sus padres reconocieron, principalmente, la necesidad de contar con un resumen médico, pautas de cuidado y confianza en el nuevo profesional.

Introduction: The shift of adolescents from a pediatric to an adult health care facility is a complex process. The objective of this study was to assess the transition/transfer process for adolescents with chronic diseases at Hospital Garrahan. Methods: Observational, cross-sectional, qualitative-quantitative study. Retrospective statistical data were obtained in relation to outpatient visits of patients aged 16-26; surveys and/or interviews were done with health care providers, adolescents, and family members from different follow-up programs. Results: The prevalence of care provided to individuals older than 16 years was 7.2%. Surveys were administered to 54 attending health care providers, 150 patients (16-26.7 years old) and 141 family members. In addition, 45 health care providers with management functions were interviewed. Health care providers: 39% had received training on transition. All identified barriers and facilitators among the different participants and facilities. They recognized the importance of encouraging autonomy among their patients, but only 30% of them interviewed their patients alone, and 56.6% delivered medical reports. Strategies: the median age of transfer was 18 years (13-20); 62% had a protocol; 84% had an informal agreement with another facility; joint or parallel care: 49%; only 20% implemented a transition plan. Patients and family members: 4.7% of adolescents attended visits alone, and health care providers had asked 45% about their autonomy and preparation to take care of their health. Adolescents and their parents had feelings (mostly negative) regarding the process and identified facilitation strategies, such as receiving a summary, knowing the new facility, and having trained health care providers. Conclusions: The transition process for adolescents with chronic diseases is still deficient and approaching it involves health care teams and the families. A lack of formal inter-institutional agreements was identified, although there were more informal agreements among health care providers; besides, the need to encourage chronically-ill patients' autonomy was also determined. In relation to facilitation strategies, patients and parents mainly recognized the need to have a medical summary, health care guidelines, and trust in the new provider.

Status of the transition/transfer process for adolescents with chronic diseases at a national pediatric referral hospital in Argentina. / Estado de situación del proceso de transición- transferencia de adolescentes con enfermedades crónicas en un hospital pediátrico de referencia nacional en Argentina.

INTRODUCTION: The shift of adolescents from a pediatric to an adult health care facility is a complex process. The objective of this study was to assess the transition/transfer process for adolescents with chronic diseases at Hospital Garrahan. METHODS: Observational, cross-sectional, qualitative-quantitative study. Retrospective statistical data were obtained in relation to outpatient visits of patients aged 16-26; surveys and/or interviews were done with health care providers, adolescents, and family members from different follow-up programs. RESULTS: The prevalence of care provided to individuals older than 16 years was 7.2%. Surveys were administered to 54 attending health care providers, 150 patients (16-26.7 years old) and 141 family members. In addition, 45 health care providers with management functions were interviewed. Health care providers: 39% had received training on transition. All identified barriers and facilitators among the different participants and facilities. They recognized the importance of encouraging autonomy among their patients, but only 30% of them interviewed their patients alone, and 56.6% delivered medical reports. Strategies: the median age of transfer was 18 years (13-20); 62% had a protocol; 84% had an informal agreement with another facility; joint or parallel care: 49%; only 20% implemented a transition plan. Patients and family members: 4.7% of adolescents attended visits alone, and health care providers had asked 45% about their autonomy and preparation to take care of their health. Adolescents and their parents had feelings (mostly negative) regarding the process and identified facilitation strategies, such as receiving a summary, knowing the new facility, and having trained health care providers. CONCLUSIONS: The transition process for adolescents with chronic diseases is still deficient and approaching it involves health care teams and the families. A lack of formal inter-institutional agreements was identified, although there were more informal agreements among health care providers; besides, the need to encourage chronically-ill patients' autonomy was also determined. In relation to facilitation strategies, patients and parents mainly recognized the need to have a medical summary, health care guidelines, and trust in the new provider.

INTRODUCCIÓN: El pasaje de adolescentes de un centro pediátrico a otro de adultos es un proceso complejo. El objetivo fue evaluar el proceso de transición-transferencia de adolescentes con enfermedades crónicas en el Hospital Garrahan. MÉTODOS: Estudio observacional, transversal, cualicuantitativo. Se obtuvieron datos estadísticos retrospectivos sobre la consulta ambulatoria de pacientes de 16-26 años y se realizaron encuestas y/o entrevistas a profesionales, adolescentes y familiares de diferentes programas de seguimiento. RESULTADOS: La prevalencia de atención a mayores de 16 años fue 7,2%. Se encuestaron 54 profesionales asistentes, 150 pacientes (16- 26,7 años) y 141 familiares. Se entrevistó a 45 profesionales con cargos de gestión. Profesionales: el 39% recibió capacitación en transición. Todos identificaron obstáculos y facilitadores en los diferentes actores e instituciones intervinientes. Reconocieron la importancia en fomentar la autonomía en sus pacientes, pero solo 30% los entrevistaba solos y 56,6% les entregaba informes médicos. Estrategias: la mediana de edad de transferencia fue18 años (13-20); 62% tenía un protocolo; 84%, un acuerdo informal con otra institución; atención conjunta o paralela: 49%;solo 20% utilizaba un plan de transición. Pacientes y familiares: 4,7% de los adolescentes concurrían solos a las consultas y el profesional le había preguntado al 45% sobre su autonomía y preparación para cuidar su salud. Los adolescentes y sus padres percibían sensaciones asociadas al proceso (con predominio, negativas) e identificaban estrategias facilitadoras, como contar con un resumen, conocer el nuevo lugar y profesionales formados. CONCLUSIONES: El proceso de transición del adolescente con enfermedad crónica es aún deficitario y su abordaje incluye a los equipos de salud y a las familias. Se identificaron falta de acuerdos interinstitucionales formales, aunque sí mayores acuerdos informales entre los profesionales, y la necesidad de fomentar la autonomía del paciente crónico. Entre las estrategias facilitadoras, los pacientes y sus padres reconocieron, principalmente, la necesidad de contar con un resumen médico, pautas de cuidado y confianza en el nuevo profesional.

Therapeutic monitoring of pediatric transplant patients with conversion to generic tacrolimus.

OBJECTIVE: Therapeutic monitoring during interchange of tacrolimus commercial formulations is essential to ensure similar exposure in transplant patients. However, there are limited data in the pediatric transplant population. This study aims to evaluate exposure, safety and efficacy in maintenance pediatric transplant patients under generic tacrolimus substitution. METHOD: Pediatric patients who underwent interchange of tacrolimus formulations were detected by the Service of Pharmacy and included in this study. Tacrolimus trough levels (C0), laboratory parameters and clinical characteristics were recorded before and after the switch. Statistical analysis was performed using Wilcoxon matched pair t-test. RESULTS: In total, 10 patients with kidney, liver, heart and hematopoietic stem cell transplantation received the innovator and switched to the generic product. The median (range) of the C0 normalized by the dose before and after switch was 74.8 [(ng/ml)/(mg/kg)] (13.8-518.4) and 65.1 [(ng/ml)/(mg/kg)] (13.5-723.5), respectively (p>0.05). Tacrolimus dose was 0.070(mg/kg) (0.024-0.461) and 0.069(mg/kg) (0.017- 0.571) for the innovator and generic formulation, respectively, with no difference when comparing both values (p>0.05). Laboratory parameters did not change after conversion (p>0.05). Adverse events, acute rejection, death and graft loss were not observed. CONCLUSION: In our study population, no significant differences in terms of laboratory parameters, drug exposure and dose were observed. We emphasize the need of close monitoring to ensure a safe interchange, especially in vulnerable populations such as the pediatric.

Objetivo: La monitorización terapéutica durante el intercambio de marcas comerciales de inmunosupresores es esencial para mantener una similar exposición al fármaco en pacientes trasplantados. Sin embargo, la información disponible en trasplante pediátrico es limitada. El objetivo del trabajo fue evaluar la exposición, seguridad y eficacia en pacientes pediátricos trasplantados en etapa de mantenimiento, sujetos a intercambio entre el producto innovador y el genérico de tacrolimus. Método: El Área de Farmacia del hospital detectó aquellos pacientes sujetos a intercambio de formulaciones según la disponibilidad de medicamentos. Se obtuvieron las concentraciones de tacrolimus en el valle (C0), parámetros de laboratorio y características clínicas antes y después del intercambio. El análisis estadístico se realizó mediante el test de muestras pareadas de Wilcoxon. Resultados: Se incluyeron 10 pacientes con trasplante renal, hepático, cardíaco y de células hematopoyéticas. La mediana (rango) del C0 normalizado por la dosis pre y post intercambio fue 74,8[(ng/ml)/(mg/kg)](13,8-518,4) y 65,1[(ng/ml)/(mg/kg)] (13,5-723,5), respectivamente (p>0,05). La dosis de tacrolimus fue 0,070(mg/kg) (0,024-0,461) y 0,069(mg/kg) (0,017-0,571) para el innovador y el genérico, respectivamente (p>0,05). Los parámetros de laboratorio de funcionalidad renal y hepática no cambiaron con la conversión de marcas (p>0,05). No se observaron eventos adversos, rechazo agudo, muerte o pérdida del injerto durante el periodo analizado. Conclusiones: En la población estudiada, no se observaron diferencias significativas en los parámetros de laboratorio, exposición al tacrolimus o dosis en el intercambio de marcas comerciales. Destacamos el rol de la monitorización terapéutica a la hora de garantizar una sustitución segura, especialmente en poblaciones vulnerables.

Validación español-argentina del cuestionario de transición a la atención médica del adulto en adolescentes con enfermedades crónicas / Validation of the Argentine Spanish version of Transition Readiness Assessment Questionnaire for adolescents with chronic conditions

Introducción. El pasaje de adolescentes con enfermedades crónicas al seguimiento como adultos es un proceso complejo y creciente. Los pacientes necesitan adquirir conocimientos y habilidades que aseguren la continuidad de su cuidado. El objetivo fue llevar a cabo la validación del instrumento Transition Readiness Assessment Questionnaire (TRAQ) 5.0, versión en español argentino, en adolescentes y adultos jóvenes con enfermedades crónicas. Población y métodos. Estudio descriptivo, transversal y cuantitativo. Se incluyeron pacientes mayores de 14 años con enfermedad crónica atendidos en el Hospital Garrahan. El TRAQ incluye 20 ítems en 5 subescalas (medicación, asistencia a citas, seguimiento de problemas de salud, comunicación con profesionales, manejo de actividades cotidianas) y se responde de modo autoadministrado. Los pacientes completaron el TRAQ, una encuesta de opinión sobre su uso y otra escala de autopercepción de autonomía; sus médicos, una escala sobre el compromiso de la enfermedad. Se registraron variables sociodemográficas, clínicas y relacionadas con el TRAQ. Resultados. Participaron 191 pacientes. El TRAQ 5.0 pudo ser comprendido y completado por la mayoría de los pacientes (96,3%), en forma autoadministrada, en poco tiempo (mediana: 5 minutos) y con poca o ninguna ayuda (81%). Presentar pobreza o escolaridad no acorde aumentó la necesidad de ayuda. La consistencia interna (alfa de Cronbach) para la puntuación total fue 0,81. Se demostró validez de construcción al testear diferentes hipótesis (todas p < 0,05): discriminación según edad ≥ 16 años (3,01 vs. 3,34), sexo (mujeres: 3,38 > varones: 3,12) y presencia de proyecto futuro (sin: 3,01 < con: 3,34); correlación con escala de autopercepción (r: 0,49). Conclusión. El TRAQ 5.0 queda disponible para ser utilizado en adolescentes argentinos con enfermedades crónicas.

Introduction. The transition of adolescents with chronic conditions to adult follow-up care is an increasingly complex process. Patients need to acquire knowledge and skills that ensure continuity of their care. The goal of this study was to validate the Argentinian Spanish version of the Transition Readiness Assessment Questionnaire (TRAQ) 5.0 tool in adolescents and young adults with chronic conditions. Population and methods. Descriptive, crosssectional, quantitative study. Patients with chronic conditions aged 14 years or older treated at Hospital Garrahan were included. The TRAQ is made up of 20 items divided into 5 subscales (Managing Medication, Appointment Keeping, Tracking Health Issues, Talking with Providers, Managing Daily Activities), and is designed to be self-administered. Patients completed the TRAQ, as well as an opinion survey about its use and a self-perceived autonomy scale; their physicians answered a scale about patients' health impairment due to the condition. Sociodemographic, clinical and TRAQ-related variables were recorded. Results. A total of 191 patients participated. The majority of patients (96.3%) understood the TRAQ 5.0 questionnaire and completed it correctly, in self-administered modality, in a short time (median: 5 minutes), with little or no help (81%). Patients who live in poverty or have a lower education level than the one expected for their age needed more help. Internal consistency (Cronbach's alpha) for the overall score was 0.81. Construct validity was demonstrated by testing different hypotheses (all p < 0.05): discriminationby age ≥ 16 years (3.01 vs. 3.34), sex (women: 3.38 > men: 3.12) and having plans for the future (without plans: 3.01 < with plans: 3.34); correlation with self-perception scale (r= 0.49). Conclusion. The TRAQ 5.0 tool is available for use inArgentinianadolescents with chronic conditions.

Validation of the Argentine Spanish version of Transition Readiness Assessment Questionnaire for adolescents with chronic conditions. / Validación español-argentina del cuestionario de transición a la atención médica del adulto en adolescentes con enfermedades crónicas.

INTRODUCTION: The transition of adolescents with chronic conditions to adult follow-up care is an increasingly complex process. Patients need to acquire knowledge and skills that ensure continuity of their care. The goal of this study was to validate the Argentinian Spanish version of the Transition Readiness Assessment Questionnaire (TRAQ) 5.0 tool in adolescents and young adults with chronic conditions. POPULATION AND METHODS: Descriptive, crosssectional, quantitative study. Patients with chronic conditions aged 14 years or older treated at Hospital Garrahan were included. The TRAQ is made up of 20 items divided into 5 subscales (Managing Medication, Appointment Keeping, Tracking Health Issues, Talking with Providers, Managing Daily Activities), and is designed to be self-administered. Patients completed the TRAQ, as well as an opinion survey about its use and a self-perceived autonomy scale; their physicians answered a scale about patients' health impairment due to the condition. Sociodemographic, clinical and TRAQ-related variables were recorded. RESULTS: A total of 191 patients participated. The majority of patients (96.3%) understood the TRAQ 5.0 questionnaire and completed it correctly, in self-administered modality, in a short time (median: 5 minutes), with little or no help (81%). Patients who live in poverty or have a lower education level than the one expected for their age needed more help. Internal consistency (Cronbach's alpha) for the overall score was 0.81. Construct validity was demonstrated by testing different hypotheses (all p < 0.05): discrimination by age ≥ 16 years (3.01 vs. 3.34), sex (women: 3.38 > men: 3.12) and having plans for the future (without plans: 3.01 < with plans: 3.34); correlation with self-perception scale (r= 0.49). CONCLUSION: The TRAQ 5.0 tool is available for use in Argentinian adolescents with chronic conditions.

Introducción. El pasaje de adolescentes con enfermedades crónicas al seguimiento como adultos es un proceso complejo y creciente. Los pacientes necesitan adquirir conocimientos y habilidades que aseguren la continuidad de su cuidado. El objetivo fue llevar a cabo la validación del instrumento Transition Readiness Assessment Questionnaire (TRAQ) 5.0, versión en español argentino, en adolescentes y adultos jóvenes con enfermedades crónicas. Población y métodos. Estudio descriptivo, transversal y cuantitativo. Se incluyeron pacientes mayores de 14 años con enfermedad crónica atendidos en el Hospital Garrahan. El TRAQ incluye 20 ítems en 5 subescalas (medicación, asistencia a citas, seguimiento de problemas de salud, comunicación con profesionales, manejo de actividades cotidianas) y se responde de modo autoadministrado. Los pacientes completaron el TRAQ, una encuesta de opinión sobre su uso y otra escala de autopercepción de autonomía; sus médicos, una escala sobre el compromiso de la enfermedad. Se registraron variables sociodemográficas, clínicas y relacionadas con el TRAQ. Resultados. Participaron 191 pacientes. El TRAQ 5.0 pudo ser comprendido y completado por la mayoría de los pacientes (96,3%), en forma autoadministrada, en poco tiempo (mediana: 5 minutos) y con poca o ninguna ayuda (81%). Presentar pobreza o escolaridad no acorde aumentó la necesidad de ayuda. La consistencia interna (alfa de Cronbach) para la puntuación total fue 0,81. Se demostró validez de construcción al testear diferentes hipótesis (todas p < 0,05): discriminación según edad ≥ 16 años (3,01 vs. 3,34), sexo (mujeres: 3,38 > varones: 3,12) y presencia de proyecto futuro (sin: 3,01 < con: 3,34); correlación con escala de autopercepción (r: 0,49). Conclusión. El TRAQ 5.0 queda disponible para ser utilizado en adolescentes argentinos con enfermedades crónicas.

Validación del índice de comorbilidad para trasplante hematopoyético en una cohorte retrospectiva de niños y adolescentes argentinos receptores de trasplante alogénico / Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in a retrospective cohort of children and adolescents who received an allogeneic transplantation in Argentina

Introducción. El trasplante hematopoyético es una terapia con riesgo de mortalidad relacionada con el trasplante (MRT), que puede variar según la comorbilidad previa. El índice de comorbilidad para trasplante hematopoyético (ICTH) es un instrumento desarrollado para medir este riesgo. Los reportes sobre su uso en pediatría son escasos. El objetivo de este estudio fue validar el ICTH en una cohorte pediátrica de receptores de trasplante hematopoyético alogénico en Argentina. Población y métodos. Cohorte retrospectiva de 140 pacientes trasplantados en el Hospital J. P. Garrahan entre 2008 y 2012. Se revisaron, de las historias clínicas, sus antecedentes y evolución. Se calculó el ICTH de cada paciente y se clasificaron como de riesgo bajo (puntaje 0), intermedio (puntaje 1-2) o alto (puntaje > 3). Se estimó la supervivencia para cada grupo por el método de Kaplan-Meier y se comparó con la prueba de logaritmos de rangos. En el caso de las enfermedades malignas, la recaída fue considerada un evento competitivo con la MRT. Se consideró significativa una p < 0,05. Resultados. La mediana del ICTH fue 1 (r: 0-6). El 45,7% de los pacientes tuvieron puntaje 0; el 40,7%, 1-2; y el 13,6%, > 3. Las comorbilidades más frecuentes fueron obesidad, infección y compromiso pulmonar y hepático. La MRT de los pacientes con puntaje 0 fue 14,1%; con puntaje 1-2, 43,7%; y con puntaje > 3, 52,6%. Las curvas de supervivencia manifestaron diferencias entre los tres grupos (p 0,01). Conclusión. El ICTH mostró ser una herramienta efectiva para predecir el riesgo de MRT en nuestro medio.

Introduction. Hematopoietic cell transplantationis a therapy with a risk of transplant-related mortality (TRM), which may vary depending on prior comorbidities. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an instrument developed to measure this risk. There are very few reports on its use in pediatrics. The objective of this study was to validate the HCT-CI in a pediatric cohort of allogeneic hematopoietic-cell transplantation recipients in Argentina. Population and methods. Retrospective cohort made up of 140 transplant patients at Hospital J. P. Garrahan between 2008 and 2012. Medical records were reviewed to identify patient history and course. The HCT-CI was estimated for each patient, who was classified as having a low (score: 0), intermediate (score: 1-2) or high (score: >3) risk. Survival was estimated for each group using the Kaplan-Meier method and compared with the log-rank test. For malignancies, relapse was considered an event consistent with TRM. A p value <0.05 was considered significant. Results. The median score in the HCT-CI was 1 (r: 0-6). A score of 0 was observed in 45.7% of patients, 1-2 in 40.7%, and >3 in 13.6%. The most common comorbidities included obesity, infection, pulmonary and liver involvement. TRM was 14.1% among patients with a score of 0; 43.7% with a score of 1-2, and 52.6% with a score >3. Differences were observed among the survival curves of the three groups (p = 0.01). Conclusion. The HCT-CI demonstrated to be an effective tool to predict the risk of TRM in our setting.

Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in a retrospective cohort of children and adolescents who received an allogeneic transplantation in Argentina. / Validación del índice de comorbilidad para trasplante hematopoyético en una cohorte retrospectiva de niños y adolescentes argentinos receptores de trasplante alogénico.

INTRODUCTION: Hematopoietic cell transplantationis a therapy with a risk of transplant-related mortality (TRM), which may vary depending on prior comorbidities. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) is an instrument developed to measure this risk. There are very few reports on its use in pediatrics. The objective of this study was to validate the HCT-CI in a pediatric cohort of allogeneic hematopoietic-cell transplantation recipients in Argentina. POPULATION AND METHODS: Retrospective cohort made up of 140 transplant patients a, Hospital J. P. Garrahan between 2008 and 2012. Medical records were reviewed to identify patient history and course. The HCT-CI was estimated for each patient, who was classified as having a low (score: 0), intermediate (score: 1-2) or high (score: >3) risk. Survival was estimated for each group using the Kaplan-Meier method and compared with the log-rank test. For malignancies, relapse was considered an event consistent with TRM. A p value 〈 0.05 was considered significant. RESULTS: The median score in the HCT-CI was 1 (r: 0-6). A score of 0 was observed in 45.7% of patients, 1-2 in 40.7%, and >3 in 13.6%. The most common comorbidities included obesity, infection, pulmonary and liver involvement. TRM was 14.1% among patients with a score of 0; 43.7% with a score of 1-2, and 52.6% with a score >3. Differences were observed among the survival curves of the three groups (p = 0.01). CONCLUSIONS: The HCT-CI demonstrated to be an effective tool to predict the risk of TRM in our setting. KEY WORDS: comorbidity, hematopoietic stem cell transplantation, non-relapse mortality, pediatrics.

INTRODUCCIÓN: El trasplante hematopoyético es una terapia con riesgo de mortalidad relacionada con el trasplante (MRT), que puede variar según la comorbilidad previa. El índice de comorbilidad para trasplante hematopoyético (ICTH) es un instrumento desarrollado para medir este riesgo. Los reportes sobre su uso en pediatría son escasos. El objetivo de este estudio fue validar el ICTH en una cohorte pediátrica de receptores de trasplante hematopoyético alogénico en Argentina. POBLACIÓN Y MÉTODOS: Cohorte retrospectiva de 140 pacientes trasplantados en e, Hospital J. P. Garrahan entre 2008 y 2012. Se revisaron, de las historias clínicas, sus antecedentes y evolución. Se calculó el ICTH de cada paciente y se clasificaron como de riesgo bajo (puntaje 0), intermedio (puntaje 1-2) o alto (puntaje 〉 3). Se estimó la supervivencia para cada grupo por el método de Kaplan-Meier y se comparó con la prueba de logaritmos de rangos. En el caso de las enfermedades malignas, la recaída fue considerada un evento competitivo con la MRT. Se consideró significativa una p 〈 0,05. RESULTADOS: La mediana del ICTH fue 1 (r: 0-6). El 45,7% de los pacientes tuvieron puntaje 0; el 40,7%, 1-2; y el 13,6%, 〉 3. Las comorbilidades más frecuentes fueron obesidad, infección y compromiso pulmonar y hepático. La MRT de los pacientes con puntaje 0 fue 14,1%; con puntaje 1-2, 43,7%; y con puntaje 〉 3, 52,6%. Las curvas de supervivencia manifestaron diferencias entre los tres grupos (p 0,01). CONCLUSIONES: El ICTH mostró ser una herramienta efectiva para predecir el riesgo de MRT en nuestro medio.

Allogeneic hematopoietic stem cell transplantation in pediatric myelodysplastic syndromes: a multicenter experience from Argentina.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (AHSCT) represents the only curative treatment for the majority of pediatric patients with Myelodysplastic Syndrome (MDS). We aimed to evaluate overall survival (OS), disease-free survival (DFS), non-relapse mortality (NRM) and relapse incidence in children who underwent AHSCT for MDS in six institutions from Argentina. PROCEDURE: A retrospective analysis of 54 AHSCT was carried out in 52 patients (mean age: 9 years; range: 2-19; 35 males). RESULTS: MDS subtypes were refractory cytopenia of childhood (RCC) (n: 26, 50%), refractory anemia with excess blasts (RAEB) (n: 9, 18%), RAEB in transformation (RAEB-T) (n: 8, 15%) and juvenile myelomonocytic leukemia (JMML) (n: 9, 17%). At time of transplant, seven (13%) patients transformed to acute myeloid leukemia (AML) and two patients with RCC to RAEB. Donors were related in 32 cases (59%) and the stem cells source was: bone marrow (63%), peripheral blood (26%), and umbilical cord blood (11%). Five-year DFS and OS were 50% and 55% respectively; and for patients with JMML, 57% and 67% respectively. Cumulative incidence of NRM and relapse were 27% and 21% respectively. In the multivariate analysis, umbilical cord blood (HR 4.07; P = 0.025) and age ≥ 9 years at transplantation (HR 3.28; P = 0.017) were associated with lower OS; age and graft-versus-host disease (GVHD) had a higher NRM. CONCLUSIONS: In our series, more than half of the patients achieved long term OS with AHSCT. Less toxic conditioning regimens or more intensive GVHD prophylaxis could lead to better results in some children.

Infecciones del sistema nervioso central en receptores de trasplante de células progenitoras hematopoyéticas / Infections of the central nervous system in hematopoietic stem cell transplant recipients

Objetivo: Describir y analizar las infecciones del sistema nervioso entral (SNC ) en una cohorte de pacientes pediátricos eceptores de trasplante de células progenitoras hematopoyéticas TCPH). Pacientes y métodos: Estudio descriptivo, etrospectivo de cohorte. Se incluyeron pacientes trasplantados ntre 1994 y 2012. Se registraron sus características generales, tipo de trasplante y fuente de células progenitoras hematopoyéticas (CPH), momento de presentación de la infección, relación de la misma con el periodo de neutropenia, enfermedad de injerto contra huésped (EICH) aguda o crónica, el tratamiento recibido y la evolución posterior. Resultados: se registraron 12 casos de infección del SNC que representa un 3,3% sobre el total de TCPH. El 75% fueron varones y la mediana de edad fue 11 años (rango 1-16). El 25% de los casos eran receptores de TCPH no familiares. La fuente de CPH fue médula ósea (MO) en el 58%, sangre de cordón umbilical (SCU) en el 33% y sangre periférica (SP) en el 9%. La etiología más frecuente (58%) fue viral (Herpes simple, Herpes 6, CMV, Varicela zoster, JC y enterovirus) seguida por las infecciones fúngicas (25%), principalmente por Aspergillus spp. e Histoplasmosis, y el compromiso del SNC por Toxoplasma gondii (17%). Cinco pacientes fallecieron a causa de la infección del SNC y solo tres sobrevivieron a largo plazo. Se encontró una fuerte asociación entre infección del SNC y el uso de SCU como fuente de CPH (SCU 18%, MO 0,7%, SP 2,8% p< 0,01) y una tendencia a un mayor número de infecciones del SNC en los receptores de TCPH no familiares respecto a los receptores de TCPH familiares (8,1% vs 2,1% p 0,06). Conclusión: Las infecciones del SNC son una complicación poco frecuente pero muy grave del TCPH. Su sospecha debe inducir a realizar rápidamente de estudios de imágenes, del LCR y, de ser necesario, otros estudios invasivos como biopsia cerebral.

Aim: To describe and analyze infections of the central nervous system (CNS) in a cohort of pediatric patients who underwent hematopoietic stem cell transplantation (HSCT). Patients and methods: A retrospective, descriptive cohort study was conduc-ted. Patients who underwent HSCT between 1994 and 2012 were included. General features, type of transplant and sour-ce of hematopoietic stem cells (HSC), onset of the infection, association between onset of infection and duration of neu-tropenia, acute or chronic graft-versus-host disease (GVHD), treatment, and outcome were recorded. Univariate analysis of the association with acute or chronic GVHD, type of transplant, ! " # !$ CNS infection - 3.3% of all HSCT - were registered. Median age of the patients was 11 years (range 1-16) and 75% were...

Índices eritrocitarios en la esferocitosis hereditaria / Erythrocyte indexes in hereditary spherocytosis

La esferocitosis hereditaria es un grupo heterogéneo de desórdenes caracterizados por la variabilidad en la clínica, en los defectos proteicos del citoesqueleto eritrocitario y en el tipo de herencia. Se estudió la sensibilidad y especificidad de la concentración de hemoglobina corpuscular media (CHCM) y el índice de amplitud de distribución eritrocitaria (ADE) en el screening diagnóstico de la esferocitosis hereditaria. Noventa y cuatro pacientes fueron comparados con niños sanos de igual sexo y edad. Todos los índices se obtuvieron por impedancia eléctrica (autoanalizador hematológico Coulter JT). En los pacientes con esferocitosis hereditaria, la CHCM (35.67±1.33 g/dl) y el ADE (20.60±4.5%), fueron significativamente más elevados que en el grupo control (CHCM 33.48±0.68 g/dl, p 0.000; ADE 13.22±0.9%, p 0.000). Con los valores de corte utilizados en nuestro laboratorio (CHCM ≥ 34.5 g/dl; ADE ≥ 14.5%) ambos índices elevados mostraron una sensibilidad de 81% y una especificidad de 98.9% en el screening de esferocitosis hereditaria. La combinación de ambos índices es un excelente predictor para el diagnóstico de esferocitosis hereditaria.

Hereditary spherocytosis is a group of heterogenous disorders characterized by variability in its clinical manifestations, membrane protein defects and inheritance. We analysed the sensitivity and specificity of mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW) in the diagnostic screening of hereditary spherocytosis. Ninetyfour patients were compared to equal number of healthy, age-matched children. All indexes were derived from measurements obtained by aperture impedance (Coulter Counter Model JT). In patients with hereditary spherocytosis, MCHC (35.67±1.33 g/dl) and RDW (20.60±4.5%) were significantly higher than in normal control subjects (MCHC 33.48±0.68 g/dl, p: 0.000; RDW 13.22±0.9%, p: 0.000). By using a cutoff for the MCHC of 34.5 g/dl and for the RDW of 14.5%, both indexes showed a sensitivity of 81% and a specificity of 98.9%. The combination of the two test is an excellent predictor for the diagnosis of hereditary spherocytosis.

Hb Alesha [beta67(E11)Val-->Met, GTG-->ATG] in an Argentinean girl.

Hb Alesha is caused by a GTG-->ATG mutation at codon 67 of the beta-globin gene, resulting in abnormal beta-globin chains in which the normal beta67(E11) valine is changed to methionine. This hemoglobin (Hb) is also known as Hb Bristol, the first unstable Hb described, since in a fraction of the variant the methionine is modified into an aspartic acid by a posttranslational modification. This replacement disrupts the apolar bonds between the valine and the heme group, producing an unstable Hb and severe hemolysis. We have identified this rare hemoglobinopathy in an Argentinean girl with severe hemolytic anemia, splenomegaly and frequent requirement for red blood cell transfusions.

[Erythrocyte indexes in hereditary spherocytosis]. / Indices eritrocitarios en la esferocitosis hereditaria.

Hereditary spherocytosis is a group of heterogenous disorders characterized by variability in its clinical manifestations, membrane protein defects and inheritance. We analysed the sensitivity and specificity of mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW) in the diagnostic screening of hereditary spherocytosis. Ninety-four patients were compared to equal number of healthy, age-matched children. All indexes were derived from measurements obtained by aperture impedance (Coulter Counter Model JT). In patients with hereditary spherocytosis, MCHC (35.67+/-1.33 g/dl) and RDW (20.60+/-4.5%) were significantly higher than in normal control subjects (MCHC 33.48+/-0.68 g/dl, p: 0.000; RDW 13.22+/-0.9%, p: 0.000). By using a cutoff for the MCHC of 34.5 g/dl and for the RDW of 14.5%, both indexes showed a sensitivity of 81% and a specificity of 98.9%. The combination of the two test is an excellent predictor for the diagnosis of hereditary spherocytosis.