Fanconi anemia and haploidentical stem cell transplantation.

BACKGROUND: Fanconi anemia is a congenital disorder belonging to bone marrow syndromes, with a risk of developing malignancy. Hematopoietic stem cell transplantation is the only curative treatment in these cases. Here, we aimed to report our clinical experience in pediatric patients with Fanconi anemia treated with haploidentical stem cell transplantation and post-transplant cyclophosphamide, an alternative strategy. METHODS: We performed a case report based on clinical records of two patients who signed the informed consent form and were treated at Fundación Valle del Lili. RESULT: Two pediatric patients, both with reduced-intensity conditioning, prophylaxis for acute graft-versus-host disease with post-transplant cyclophosphamide. They achieved primary neutrophil/platelets engraftment, and 100% chimerism. Had grade I or II graft-versus-host disease resolved? Currently are alive and in complete remission. CONCLUSIONS: The use of mismatched related donors for haploidentical stem cell transplantation and post-transplant cyclophosphamide might be a promising option, and well-tolerated in pediatric patients. Serial chimerism can be useful during follow-up.

Risk factors and incidence of cytomegalovirus viremia and disease in pediatric patients with allogeneic hematopoietic stem cell transplantation: An 8-year single-center experience in Latin America.

BACKGROUND: Cytomegalovirus infection represents a significant cause of morbidity and mortality after hematopoietic stem cell transplantation. This study aimed to evaluate the incidence of viremia and disease due to cytomegalovirus and the risk factors in pediatric patients with hematopoietic stem cell transplantation in our institution. METHODS: This was a retrospective cohort of patients under 19 years of age who underwent allogeneic hematopoietic stem cell transplantation due to any indication between 2012 and 2019. The analysis included the diagnosis of cytomegalovirus viremia or disease during post-transplant follow-up, evaluation of risk factors, and outcomes. The statistical analysis included univariate and multivariate analyses, and the cumulative incidence of cytomegalovirus viremia was determined by the Kaplan-Meier method using STATA 14 statistical software. RESULTS: A total of 182 transplants were included. At 100 days, the cumulative incidence of cytomegalovirus viremia was 70.5%, and that of cytomegalovirus disease was 4.7%. Overall survival at 2 years was 74%, and event-free survival was 64%. The remaining demographic characteristics were not predictors of infection. There was no association between viremia and relapse or survival of the patients. Higher mortality was noted in cytomegalovirus disease. CONCLUSIONS: During the study period, the incidence of cytomegalovirus disease was similar to that of other pediatric reports, but the incidence of viremia was higher. Pre-emptive therapy has diminished disease rates and death due to infection. Viral load cutoff points should be standardized to guide treatment and avoid myelotoxicity.

Haploidentical Stem Cell Transplant with Post-Transplant Cyclophosphamide in Pediatric Hemophagocytic Lymphohistiocytosis.

PURPOSE: Primary hemophagocytic lymphohistiocytosis is a severe and uncommon disease affecting pediatric patients. Genetic abnormalities have been related to altered apoptosis and exaggerated inflammatory reactions. Chemoimmunotherapy and stem cell transplantation are treatment options, but transplant is the only curative treatment. Here we aim to describe the treatment with hematopoietic stem cell transplantation with a novel strategy and the outcomes. METHODS: An observational, descriptive, case series study was performed in pediatric patients of two high complexity medical centers in Colombia. Data was collected retrospectively between 2015 and 2020. RESULTS: We describe five pediatric cases with a diagnosis of primary hemophagocytic lymphohistiocytosis. All were treated with replete-cell haploidentical hematopoietic stem transplantation, reduced-intensity conditioning, and post-transplant cyclophosphamide, in two high-complexity centers in Colombia. All patients are alive, and one is receiving management for chronic graft-versus-host disease. CONCLUSION: To the best of our knowledge, there are few reports in the literature with this strategy, promising a possible alternative when there are no other donor options.

Hematopoietic Stem Cell Transplantation in Children with Inborn Errors of Immunity: a Multi-center Experience in Colombia.

PURPOSE: To characterize the pediatric population with inborn errors of immunity (IEI) that was treated with hematopoietic stem cell transplantation (HSCT) in three reference centers in Colombia. What have been the characteristics and outcomes of hematopoietic stem cell transplantation in pediatric patients with inborn errors of immunity in three reference care centers in Colombia between 2007 and 2018? METHODS: We conducted an observational, retrospective cohort study in children with a diagnosis of IEI who underwent HSCT between 2007 and 2018. RESULTS: Forty-seven patients were identified, and 5 were re-transplanted. Sixty-eight percent were male. The median age at diagnosis was 0.6 years, and for HSCT was 1.4 years. The most common diseases were chronic granulomatous disease (38%) followed by severe combined immune deficiencies (19%) and hemophagocytic lymphohistiocytosis (15%). Cord blood donors were the most used source of HSCT (44%). T cell-replete grafts from haploidentical donors using post-transplantation cyclophosphamide represent 37% of the cohort. All patients received conditioning, 62% with a non-myeloablative regimen. Calcineurin inhibitors were the main graft-versus-host disease prophylaxis (63.8%). Acute graft-versus-host disease developed in 35% of the total patients. The most frequent post-transplant infections were viral and fungal infections. The 1-year overall survival rates for the patients who received HSCT from identical, haploidentical, and cord sources were 80%, 72%, and 63%, respectively. The 5-year overall survival was 63%. CONCLUSIONS: HSCT is a curative treatment option for some IEI and can be performed with any donor type. Early and timely treatment in referral centers can improve survival.

Outcomes in pediatrics patients diagnosed with bone marrow failure disorders treated in a tertiary care center. / Desenlace de los pacientes pediátricos con falla medular tratados en un centro de alta complejidad.

INTRODUCTION: Bone marrow failure (BMF) syndromes are rare disorders with an annual incidence of 2-4 cases per million. Treatment options include immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT). OBJECTIVE: To analyze the outcomes of pediatric patients diagnosed with BMF treated in a tertiary care center. PATIENTS AND METHOD: Retrospective study of pediatric patients diagnosed with BMF who consulted at Fundación Valle de Lili, Cali. Descriptive statistical analysis was performed according to Acquired BMF (ABMF) and Inherited BMF (IBMF). The outcomes include treatment, complications, overall survival (OS) in transplant patients, calculated using the Kaplan Meier method. RESULTS: We included 24 patients with BMF, average age 6.5 ± 4 years, and 50% were women. 58% presented IBMF, 9 with Fanconi anemia (FA), 2 dyskeratosis congenita, 2 congenital amegakaryocytic thrombocytopenia, and 1 presented Diamond-Blackfan anemia. 12 patients treated with HSCT had a 5-year OS of 83%. ABMF represented 42%. 6 patients received IST-HSCT, 3 received IST, and 1 received HSCT. The OS of the IST-HSCT group was 86%. Six patients died, four of them related to infection. CONCLUSIONS: In this series, there was a higher number of cases with IBMF. The OS of patients treated with HSCT is similar to that reported in recent studies. The most frequent cause of death was of infectious origin which has also been previously reported. The treatment esta blished in the patients showed favorable results in a Latin American tertiary care center.

Corticosteroids for septic arthritis in children.

BACKGROUND: Septic arthritis is an acute infection of the joints characterised by erosive disruption of the articular space. It is the most common non-degenerative articular disease in developing countries. The most vulnerable population for septic arthritis includes infants and preschoolers, especially boys. Septic arthritis disproportionately affects populations of low socioeconomic status. Systemic corticosteroids and antibiotic therapy may be beneficial for treatment of septic arthritis. Even if the joint infection is eradicated by antibiotic treatment, the inflammatory process may produce residual joint damage and sequelae. OBJECTIVES: To determine the benefits and harms of corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis. SEARCH METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, Latin American Caribbean Health Sciences Literature (LILACS), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/), ClinicalTrials.gov (www.ClinicalTrials.gov), and Google Scholar. We searched all databases from their inception to 17 April 2018, with no restrictions on language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with patients from two months to 18 years of age with a diagnosis of septic arthritis who were receiving corticosteroids in addition to antibiotic therapy or as an adjuvant to other therapies such as surgical drainage, intra-articular puncture, arthroscopic irrigation, or debridement. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, data extraction, and evaluation of risk of bias. We considered as major outcomes the presence of pain, activities of daily living, normal physical joint function, days of antibiotic treatment, length of hospital stay, and numbers of total and serious adverse events. We used standard methodological procedures expected by Cochrane. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table. MAIN RESULTS: We included two RCTs involving a total of 149 children between three months and 18 years of age who were receiving antibiotics for septic arthritis. The most commonly affected joints were hips and knees. These studies were performed in Costa Rica and Israel. In both studies, dexamethasone administered intravenously (ranging from 0.15 to 0.2 mg/kg/dose every six to eight hours) during four days was the corticosteroid, and the comparator was placebo. Trials excluded patients with any degree of immunodeficiency or immunosuppression. The longest follow-up was one year. Trials did not report activities of daily living nor length of hospital stay. Both studies used adequate processes for randomisation, allocation concealment, and blinding, and review authors judged them to have low risk of selection and performance bias. Losses to follow-up were substantive in both studies, and we judged them to have high risk of attrition bias and of selective outcome reporting. We graded all outcomes as low quality due to concerns about study limitations and imprecision.The risk ratio (RR) for absence of pain at 12 months of follow-up was 1.33, favouring corticosteroids (95% confidence interval (CI) 1.03 to 1.72; P = 0.03; number needed to treat for an additional beneficial outcome (NNTB) = 13, 95% CI 6 to 139; absolute risk difference 24%, 95% CI 5% to 43%).The RR for normal function of the affected joint at 12 months of follow-up was 1.32, favouring corticosteroids (95% CI 1.12 to 1.57; P = 0.001; NNTB = 13, 95% CI 7 to 33; absolute risk difference 24%, 95% CI 11% to 37%).We found a reduction in the number of days of intravenous antibiotic treatment favouring corticosteroids (mean difference (MD) -2.77, 95% CI -4.16 to -1.39) based on two trials with 149 participants.Researchers did not report length of hospital stay. One trial (49 participants) reported that treatment with dexamethasone was associated with a shorter duration of IV antibiotic treatment, leading to a shorter hospital stay, and although duration of hospitalisation was a primary outcome of the study, study authors did not provide data on the duration of hospitalisation. We downgraded the quality by one level for concerns about study limitations (high risk of attrition bias and selective reporting), and by another level for imprecision.In one trial of 49 participants, researchers followed 29 children for 12 months, and parents reported that no children demonstrated adverse effects of the intervention. AUTHORS' CONCLUSIONS: Evidence for corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis is of low quality and is derived from the findings of two trials (N = 149). Corticosteroids may increase the proportion of patients without pain and the proportion of patients with normal function of the affected joint at 12 months, and may also reduce the number of days of antibiotic treatment. However, we cannot draw strong conclusions based upon these trial results. Additional randomised clinical trials in children with relevant outcomes are needed.

Misleading Pore Size Measurements in Gelatin and Alginate Hydrogels revealed by Confocal Microscopy.

It is a well-documented phenomenon that the porous structure of hydrogels observed with vacuum-based imaging techniques is generated during the freezing and drying process employed prior to observation. Nevertheless, vacuum-based techniques, such as scanning electron microscopy (SEM), are still being commonly used to measure pore sizes in hydrogels, which is often not representative of the actual pore size in hydrated conditions. The frequent underestimation of the impact of freezing and drying on hydrogel structures could stem from a lack of cross-fertilization between materials science and biomedical or food science communities, or from the simplicity and visually appealing nature of SEM imaging which may lead to an overemphasis on its use. Our study provides a straightforward and impactful way of pinpointing this phenomenon exploiting two hydrogels ubiquitously applied in tissue engineering, including gelatin methacryloyl (GelMA) and alginate as proof-of-concept hydrogels. By comparing images of the samples in the native hydrated state, followed by freezing, freeze-drying and rehydration using SEM and confocal microscopy, we highlight discrepancies between hydrogel pore sizes in the hydrated versus the dry state. To conclude, our study offers recommendations for researchers seeking insight in hydrogel properties and emphasizes key factors that require careful control when using SEM as a characterization tool.

Outcomes and challenges treating pediatric acute myeloid leukemia: a retrospective analysis of patients treated at the Fundación Valle del Lili between 2011 and 2020.

INTRODUCTION: Acute myeloid leukemia is a challenging disease, due to a poor prognosis in developing countries. Herein, we aim to describe the clinical characteristics and outcomes after chemotherapy and transplantation. METHODS: A retrospective analytic observational study was performed with patients under 18 years of age with newly diagnosed acute myeloid leukemia treated at a referral center in Colombia. Two groups were compared: induction therapy (IT) and induction therapy plus consolidation (IT + C). The survival analysis was performed using the Kaplan-Meier method. RESULTS: We analyzed 34 patients diagnosed with acute myeloid leukemia; 20 received hematopoietic stem cell transplantation. Most were French-American-British (FAB) classification types M1, M5 and M0. The transplantation was haploidentical in 65%, conditioning was myeloablative in 67% and graft-versus-host disease prophylaxis was performed with post-transplant cyclophosphamide in 70%. Overall, the 5-year survival was 52% and the overall 5-year survival in the transplanted group was 80%. There were 16 deaths; in the IT group, n = 12, and in the IT + C group, n = 4. In the former, the main cause of death was septic shock and in the latter, it was relapse. CONCLUSION: Transplantation is a safe option. Receiving treatment and supportive measures in hematopoietic stem cell transplantation units is necessary to avoid infections, especially during induction cycles.

Prophylaxis for invasive fungal infection in pediatric patients with allogeneic hematopoietic stem cell transplantation.

Background: Antifungal prophylaxis is recommended for hematopoietic stem cell transplantation (HSCT) to decrease the incidence of invasive fungal infections (IFI). This study aimed to compare the two groups of antifungal prophylaxis in pediatric patients undergoing allogeneic HSCT. Methods: This observational, analytic, retrospective cohort study compared the incidence of IFI with antifungal prophylaxis with voriconazole vs. other antifungals in the first 100 days after allogeneic HSCT in patients aged <18 years between 2012 and 2018. The statistical analysis included univariate and multivariate analyses and determination of the cumulative incidence of invasive fungal infection by the Kaplan‒Meier method using STATA 14 statistical software. Results: A total of 139 allogeneic HSCT were performed. The principal diagnosis was acute leukemia (63%). The 75% had haploidentical donors, and 50% used an antifungal in the month before transplantation. Voriconazole (69%) was the most frequently administered antifungal prophylaxis. The cumulative incidence of IFI was 5% (7 cases). Of the patients with IFIs, four began prophylaxis with voriconazole, one with caspofungin, and one with fluconazole. Additionally, six were possible cases, one was proven (Candida parapsilosis), and 1/7 died. Conclusion: There were no differences in the incidence of IFI between patients who received prophylaxis with voriconazole and other antifungal agents.

Impact of health-related quality of life on pediatric patients who underwent hematopoietic stem cell transplantation in a Colombian institution / Impacto de la calidad de vida relacionada a la salud en pacientes pediátricos con trasplante de progenitores hematopoyéticos en una institución colombiana.

Introduction: Hematopoietic stem cell transplantation is the curative option for some diseases and is increasing patient survival. The health-related quality of life in these patients is not systematically evaluated. Objectives: The present study sought to describe the health-related quality of life and complications in children who underwent hematopoietic stem cell transplantation. Materials and methods: A cross-sectional study was conducted on pediatric transplanted survivors. Health-related quality of life was measured using the KIDSCREEN-27 scale and Short Form-12 (SF-12) in patients between 8 and 14 years of age and those over 14 years, respectively. Statistical analysis was performed using STATA 12 software. We used the Rasch model person parameter estimates translated into T-values to score the questionnaire. Results: A total of 42 children answered the questionnaires. The most frequent adverse events were chronic graft Vs. host disease and endocrine complications. According to European norm data in the KIDSCREEN-12 scale, scores for the school dimension and social and peer support were below the 50th. percentile. The group administered immunosuppressants had lower scores on the physical component of the SF-12™ scale. Conclusions: In general, the KIDSCREEN-27 does appear to suggest some quality-of-life deficit in younger children. The scales showed reliability in this population.

Introducción. El trasplante de células madre hematopoyéticas es la opción curativa para algunas enfermedades y está aumentando el tiempo de supervivencia de los pacientes. La calidad de vida relacionada con la salud en estos pacientes no se evalúa de manera sistemática. Objetivos. Describir la calidad de vida relacionada con la salud y las complicaciones en niños con trasplante de células madre hematopoyéticas. Materiales y métodos. Es un estudio transversal en pacientes pediátricos sobrevivientes al trasplante. Se midió la calidad de vida relacionada con la salud, utilizando el cuestionario KIDSCREEN-27 en pacientes entre 8 y 14 años y la SF-12™ (Short Form-12) en pacientes mayores de 14 años. El análisis estadístico se realizó en el software Stata 12. Utilizamos el modelo de Rasch, trasladando estimación de parámetros a valores t para obtener el resultado de los cuestionarios. Resultados. En total, 42 pacientes respondieron alguno de los cuestionarios. Los eventos adversos más frecuentes fueron "enfermedad crónica de injerto Vs. contra huésped" y "complicaciones endocrinas". De acuerdo con la normalidad de datos del KIDSCREEN-27, los puntajes de las dimensiones "ambiente escolar" y "soporte social y pares" fueron inferiores al percentil 50. En el cuestionario SF-12™, el grupo que utilizaba inmunosupresores tuvo un menor puntaje en el componente físico. Conclusiones. En general, los resultados del KIDSCREEN-27 sugieren un cierto déficit de calidad de vida en pacientes entre 8 y 14 años. Los cuestionarios mostraron confiabilidad en la muestra.

Impacto de la calidad de vida relacionada a la salud en pacientes pediátricos con trasplante de progenitores hematopoyéticos en una institución colombiana / Impact of health-related quality of life on pediatric patients who underwent hematopoietic stem cell transplantation in a Colombian institution

Introducción. El trasplante de células madre hematopoyéticas es la opción curativa para algunas enfermedades y está aumentando el tiempo de supervivencia de los pacientes. La calidad de vida relacionada con la salud en estos pacientes no se evalúa de manera sistemática. Objetivos. Describir la calidad de vida relacionada con la salud y las complicaciones en niños con trasplante de células madre hematopoyéticas. Materiales y métodos. Es un estudio transversal en pacientes pediátricos sobrevivientes al trasplante. Se midió la calidad de vida relacionada con la salud, utilizando el cuestionario KIDSCREEN-27 en pacientes entre 8 y 14 años y la SF-12™ (Short Form-12) en pacientes mayores de 14 años. El análisis estadístico se realizó en el software Stata 12. Utilizamos el modelo de Rasch, trasladando estimación de parámetros a valores t para obtener el resultado de los cuestionarios. Resultados. En total, 42 pacientes respondieron alguno de los cuestionarios. Los eventos adversos más frecuentes fueron "enfermedad crónica de injerto Vs. contra huésped" y "complicaciones endocrinas". De acuerdo con la normalidad de datos del KIDSCREEN-27, los puntajes de las dimensiones "ambiente escolar" y "soporte social y pares" fueron inferiores al percentil 50. En el cuestionario SF-12™, el grupo que utilizaba inmunosupresores tuvo un menor puntaje en el componente físico. Conclusiones. En general, los resultados del KIDSCREEN-27 sugieren un cierto déficit de calidad de vida en pacientes entre 8 y 14 años. Los cuestionarios mostraron confiabilidad en la muestra.

Introduction: Hematopoietic stem cell transplantation is the curative option for some diseases and is increasing patient survival. The health-related quality of life in these patients is not systematically evaluated. Objectives: The present study sought to describe the health-related quality of life and complications in children who underwent hematopoietic stem cell transplantation. Materials and methods: A cross-sectional study was conducted on pediatric transplanted survivors. Health-related quality of life was measured using the KIDSCREEN-27 scale and Short Form-12 (SF-12) in patients between 8 and 14 years of age and those over 14 years, respectively. Statistical analysis was performed using STATA 12 software. We used the Rasch model person parameter estimates translated into T-values to score the questionnaire. Results: A total of 42 children answered the questionnaires. The most frequent adverse events were chronic graft Vs. host disease and endocrine complications. According to European norm data in the KIDSCREEN-12 scale, scores for the school dimension and social and peer support were below the 50th. percentile. The group administered immunosuppressants had lower scores on the physical component of the SF-12™ scale. Conclusions: In general, the KIDSCREEN-27 does appear to suggest some quality-of-life deficit in younger children. The scales showed reliability in this population.

Desenlace de los pacientes pediátricos con falla medular tratados en un centro de alta complejidad / Outcomes in pediatrics patients diagnosed with bone marrow failure disorders treated in a tertiary care center

INTRODUCCIÓN: Los síndromes de falla medular (SFM) son trastornos infrecuentes, con una incidencia anual de 2-4 casos por millón. Las opciones de tratamiento incluyen terapia de inmunosupresión (TIS) y restaura ción de la hematopoyesis con trasplante de progenitores hematopoyéticas (TPH). OBJETIVO: Analizar los desenlaces de pacientes pediátricos diagnosticados con SFM tratados en una institución de alta complejidad. PACIENTES Y MÉTODO: Estudio retrospectivo de pacientes pediátricos con diagnóstico de SFM que consultaron a la Fundación Valle del Lili, Cali. Se realizo análisis estadístico descriptivo según SFM adquirida (SFMA) y SFM congénita (SFMC). Los desenlaces incluyeron: tratamiento, complicaciones, supervivencia global (SG) en los trasplantados, calculada con el método Kaplan Meier. RESULTADOS: Se incluyeron 24 pacientes con SFM, edad 6,5 ± 4 años, 50% mujeres. El 58% fue ron SFMC, 9 con anemia de Fanconi, 2 disqueratosis congénita, 2 trombocitopenia amegacariocítica congénita, uno anemia Diamond-Blackfan. Doce pacientes con TPH tuvieron SG a 5 años de 83%. SFMA correspondió al 42%, 6 recibieron TIS-TPH, 3 TIS y 1 TPH, la SG del grupo con TIS-TPH fue 86%. Seis pacientes fallecieron, 4/6 relacionadas con infección. CONCLUSIONES: En esta serie fue mayor el número de casos con SFMC. La SG de los pacientes llevados a TPH es comparable con la reportada en estudios recientes. La causa de muerte predominante fue infecciosa que también se ha reportado previamente. El tratamiento instaurado en los pacientes de esta serie mostró resultados favorables en un centro de alta complejidad en un país latinoamericano.

INTRODUCTION: Bone marrow failure (BMF) syndromes are rare disorders with an annual incidence of 2-4 cases per million. Treatment options include immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT). OBJECTIVE: To analyze the outcomes of pediatric patients diagnosed with BMF treated in a tertiary care center. PATIENTS AND METHODP: Retrospective study of pediatric patients diagnosed with BMF who consulted at Fundación Valle de Lili, Cali. Descriptive statistical analysis was performed according to Acquired BMF (ABMF) and Inherited BMF (IBMF). The outcomes include treatment, complications, overall survival (OS) in transplant patients, calculated using the Kaplan Meier method. RESULTS: We included 24 patients with BMF, average age 6.5 ± 4 years, and 50% were women. 58% presented IBMF, 9 with Fanconi anemia (FA), 2 dyskeratosis congenita, 2 congenital amegakaryocytic thrombocytopenia, and 1 presented Diamond-Blackfan anemia. 12 patients treated with HSCT had a 5-year OS of 83%. ABMF represented 42%. 6 patients received IST-HSCT, 3 received IST, and 1 received HSCT. The OS of the IST-HSCT group was 86%. Six patients died, four of them related to infection. CONCLUSIONS: In this series, there was a higher number of cases with IBMF. The OS of patients treated with HSCT is similar to that reported in recent studies. The most frequent cause of death was of infectious origin which has also been previously reported. The treatment esta blished in the patients showed favorable results in a Latin American tertiary care center.