Severe Impairment of T-cell Immunity and Pulmonary GvHD Are Major Risk Factors for Nontuberculous Mycobacterial Infection After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplant recipients are prone to infectious complications. Infections caused by nontuberculous mycobacteria have increased in adults but literature in children is scarce. We report 6 episodes of disseminated or pulmonary nontuberculous mycobacteria infection among 5 pediatric hematopoietic stem cell transplant recipients. All but one were caused by Mycobacterium avium complex. Four patients died, 2 related to nontuberculous mycobacteria infection.

Use of Eculizumab in Pediatric Patients with High-Risk Transplantation-Associated Thrombotic Microangiopathy: Outcomes and Risk Factors Associated with Response and Survival. A Retrospective Study on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).

Transplantation-associated thrombotic microangiopathy (TA-TMA) is associated with high morbidity and mortality. Although survival has improved significantly with the introduction of eculizumab, the need for improvement remains, especially in high-risk patients. This study aimed to describe the results obtained with eculizumab in a pediatric cohort with the attempt to define which risk factors could determine the response to treatment. We designed a national multicenter retrospective study of children treated with eculizumab for high-risk TA-TMA. The study cohort comprised 29 patients who had undergone a first (n = 28) or second (n = 1) allogeneic hematopoietic stem cell transplantation (HSCT) for malignant (n = 17) or nonmalignant (n = 12) disease. The median time from HSCT to TA-TMA diagnosis was 154 days (interquartile range [IQR], 103 to 263 days). Eleven patients (38%) who were initially diagnosed with low- to intermediate-risk TA-TMA progressed to high-risk TA-TMA (hrTA-TMA), within a median time of 4 days (IQR, 1 to 33 days). SC5b-9 was increased in 90% of 20 patients in whom it was measured. Renal (n = 12), pulmonary (n = 1), and intestinal (n = 1) biopsy confirmed the diagnosis in 12 of 14 patients (85%). Seventeen patients (58%) had extrarenal involvement with serositis (n = 13; 44,8%), pulmonary (n = 12; 41,4%), gastrointestinal (n = 8; 27.6%), cardiovascular (n = 7; 24.1%), or central nervous system (CNS) (n = 2; 6.9%) involvement. The median time from hrTA-TMA diagnosis to the initiation of eculizumab was 7 days (IQR, 1 to 8 days). Overall, 19 patients (65.5%) responded to eculizumab, of whom 17 (58.6%) achieved a complete response and 2 (6.9%) achieved a partial response. The remaining 10 patients (34.5%) did not show any of response. The overall response rate to eculizumab for TA-TMA was 27.59% (95% confidence interval [CI], 14.87% to 47.66%) at 1 month, 55.17% (95% CI, 38.43% to 73.48%) at 3 months, and 62.07% (95% CI, 45.10% to 79.13%) at 6 months after eculizumab initiation. In multivariate analysis, the pulmonary involvement decreased the probability of response (hazard ratio [HR], .18; P = .0298). The 1-year overall survival (OS) was 55.2% (95% CI, 35.6% to 71.0%) for the whole cohort and 83.3% (95% CI, 56.7% to 94.3%) for patients who responded to eculizumab. Pulmonary involvement (HR, 14.93; P = .0043) and CNS involvement (HR, 8.63; P = .0497) were associated with a statistically significant decrease in survival. We found that patients diagnosed with hrTA-TMA with pulmonary involvement had a poor response to eculizumab, and that patients with pulmonary and CNS involvement had significantly decreased survival. Given these results, we hypothesize that providing eculizumab therapy at an early stage of the disease before organ damage is established might significantly improve the response and, consequently, survival.

The potential impact of PCV-13, PCV-15 and PCV-20 vaccines in Colombia.

PURPOSE: To provide information about which pneumococcal vaccine could have greater coverage in Colombia. METHODS: This is a retrospective analysis of patients diagnosed with invasive pneumococcal disease (IPD) between 2015 and 2019 in Bogotá, Colombia. We compared the theoretical serotype coverage of the available anti-pneumococcal vaccines (i.e., PCV-10, PCV-10 SII, PCV-13, PCV-15, PCV-20, PCV-21, PCV24, PPSV-23) and the non-vaccine-covered serotypes stratified by age. RESULTS: 690 IPD cases were included. In children ≤5 y/o, of the approved vaccines PCV-20 showed the most theoretical protection (71.3 % [149/209]), while in adults aged 18-64 y/o was PCV-20 (61.8 % [164/265]), and in those ≥65 y/o was PPSV-23 (58.1 % [100/172]) followed by PCV-20 (55.2 % [95/172]). The non-covered serotypes represented one-third of the cohort (33.9 % [234/690]), being 6C (20.5 % [48/234]), 15A (12.8 % [30/234]), and 23A (11.5 % [27/234]) the most prevalent. CONCLUSION: Introducing PCV-20 for children and PCV-20 along with a PPSV-23 booster in adults may reduce IPD frequency in all ages in Colombia. The inclusion of non-covered serotypes is required for future vaccines.

An artificial intelligence-driven predictive model for pediatric allogeneic hematopoietic stem cell transplantation using clinical variables.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a procedure with high morbidity and mortality. Identifying patients for maximum benefit and risk assessment is crucial in the decision-making process. This has led to the development of predictive risk models for HSCT in adults, which have limitations when applied to pediatric population. Our goal was to develop an automatic learning algorithm to predict survival in children with malignant disorders undergoing HSCT. METHODS: We studied allogenic HSCTs performed on children with malignant disorders at a third-level hospital between 1991 and 2021. Survival was analyzed using the Kaplan-Meier method, log-rank test for the univariate analysis, and Cox regression for the multivariate analysis. A prognostic index was constructed based on these findings. Lastly, we constructed a predictive model using a random forest algorithm to forecast 1-year survival after HSCT. RESULTS: We analyzed 229 HSCTs in 201 patients with a median follow-up of 1.64 years. Variables that impacted on the multivariate analysis were older age (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.12-1.76, p = .003), oldest period of HSCT (HR 0.46, 95% CI 0.29-0.73, p < .001), and mismatched donor (HR 2.65, 95% CI 1.51-4.65, p = .001). Our prognostic index was associated with 3-year overall survival (OS; p < .001). A random forest was developed using as variables: diagnosis, age, year of HSCT, time from diagnosis to HSCT, disease stage, donor type, and conditioning. This achieved 72% accuracy in predicting 1-year OS. CONCLUSIONS: Our index and random forest was effective in predicting 1-year survival. However, further validation in diverse populations is necessary to establish their generalizability.

Treosulfan-Based Conditioning Regimen In Pediatric Hematopoietic Stem Cell Transplantation: A Retrospective Analysis on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).

Increasing data on treosulfan-based conditioning regimens before hematopoietic stem cell transplantation (HSCT) demonstrate the consistent benefits of this approach, particularly regarding acute toxicity. This study aimed to describe the results of treosulfan-based conditioning regimens in children, focusing on toxicity and outcomes when used to treat both malignant and nonmalignant diseases. This retrospective observational study of pediatric patients treated in Spain with treosulfan-based conditioning regimens before HSCT was based on data collection from electronic clinical records. We studied a total of 160 treosulfan-based conditioning HSCTs to treat nonmalignant diseases (n = 117) or malignant diseases (n = 43) in 158 children and adolescents. The median patient age at HSCT was 5.1 years (interquartile range, 2 to 10 years). The most frequent diagnoses were primary immunodeficiency (n = 42; 36%) and sickle cell disease (n = 42; 36%) in the nonmalignant disease cohort and acute lymphoblastic leukemia (n = 15; 35%) in the malignant disease cohort. Engraftment occurred in 97% of the patients. The median times to neutrophil engraftment (17 days versus 14 days; P = .008) and platelet engraftment (20 days versus 15 days; P = .002) were linger in the nonmalignant cohort. The 1-year cumulative incidence of veno-occlusive disease was 7.98% (95% confidence interval [CI], 4.6% to 13.6%), with no significant differences between cohorts. The 1-year cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was higher in the malignant disease cohort (18% versus 3.2%; P = .011). Overall, the malignant cohort had both a higher total incidence (9% versus 3%; P < .001) and a higher 2-year cumulative incidence (16% versus 1.9%; P < .001) of total chronic GVHD. The 2-year cumulative transplantation-related mortality was 15%, with no difference between the 2 cohorts. The 5-year overall survival was 80% (95% CI, 72% to 86%) and was higher in the nonmalignant cohort (87% versus 61%; P = .01). The 2-year cumulative incidence of relapse was 25% in the malignant cohort. The 5-year cumulative GVHD-free, relapse-free survival rate was 60% (95% CI, 51% to 70%) and was higher in the nonmalignant cohort (72% versus 22%; P < .001). A treosulfan-based radiation-free conditioning regimen is feasible, achieving a high engraftment rate and 5-year overall survival, and is an emerging option for the first HSCT in nonmalignant diseases.

Younger age and induction failure predict outcomes in infant leukemia: 30 years of experience in a tertiary center.

Objectives: This study aimed to evaluate the characteristics and outcomes of infant patients with leukemia. Methods: A retrospective analysis was conducted in a cohort of 39 patients diagnosed with infant leukemia from 1990 to 2020 who underwent treatment at the pediatric hemato-oncology department of a tertiary hospital in Madrid, Spain. Results: Of the 588 diagnosed cases of childhood leukemia, 39 (6.6%) cases were infant leukemia. The 5-year event-free survival and the 5-year overall survival were 43.6% (SE 4.1) and 46.5% (SD 24.08), respectively. In a univariate analysis, a younger age at diagnosis was associated with poorer outcomes (p = 0.027), as was induction failure (p = 0.0024). Patients treated with hematopoietic stem cell transplantation had better outcomes than non-transplanted patients (p = 0.001); however, the group comparisons that exclude patients who were unable to undergo transplantation due to refractoriness/relapse or death during treatment showed no significant differences. Conclusions: The main risk factors that affected survival in our study were an age younger than 6 months and a poor response to induction therapy. It is important to identify poor prognostic factors in this population in order to seek different approaches that could improve outcomes.

Interpretación de gases arteriovenosos. Una guía práctica. Revisión de tema / Interpretation of arteriovenous gases. A practical guideline. A review

La evaluación del estado ácido base y de la oxigenación de un paciente es fundamental en cualquier escenario clínico, sea en consulta externa, en un servicio de urgencias, hospitalización, en cirugía o en la unidad de cuidado intensivo. El conocimiento de las bases fisiopatológicas es de suma importancia para el entendimiento y adecuada interpretación de estas condiciones. El objetivo de esta revisión es proveer las bases de conocimiento necesarias para el abordaje adecuado de los gases arteriovenosos y proponer un modelo para la compresión e interpretación de estos. Este artículo aborda las bases fisiopatológicas de las alteraciones ácido base, los modelos existentes en su compresión, el modelo propuesto para su abordaje diagnóstico, sus diagnósticos diferenciales, el enfoque de la hipoxemia, la interpretación de los gases arteriovenosos y las variables que se pueden obtener de estos, el enfoque de la acidosis láctica y unos ejemplos del modelo propuesto.

The evaluation of the acid-base status and the oxygenation of a patient is fundamental in any clinical setting, be it in an outpatient clinic, in an emergency service, hospitalization, in surgery or in the intensive care unit. Knowledge of the pathophysiological bases is of the utmost importance for the understanding and adequate interpretation of these conditions. The objective of this review is to provide the necessary knowledge for the adequate understanding of arteriovenous gases and to propose a model for their comprehension and interpretation. This article addresses the pathophysiological bases of acid-base disorders, the existing models in their comprehension, the model proposed for their diagnostic approach, their differential diagnoses, the diagnostic approach to hypoxemia, the interpretation of arteriovenous gases and the variables that can be obtained from them, the diagnostic approach of lactic acidosis and some examples of the proposed model.

A retrospective study of treosulfan versus busulfan-based conditioning in pediatric patients.

OBJECTIVES: To compare the outcomes of treosulfan-based vs busulfan-based conditioning regimens in allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. METHODS: Retrospective study of all consecutive patients (2012-2019) treated with allogenic HSCT and treosulfan- or busulfan-based conditioning regimens at a single center. RESULTS: A total of 101 HSCT were included: 66 HSCT with busulfan and 35 with treosulfan. In malignant diseases (n = 62), busulfan-based conditioning was more commonly employed than treosulfan: 82.3% vs 17.7%. However, the use of treosulfan for malignant diseases increased over time: 6.5% of HSCT in 2012-2015 vs 29% of HSCT in 2015-2019 (p = .02). The cohort of treosulfan had more children under 1-year of age than the busulfan cohort (31 vs 13%; p = .033). The percentage of patients who received serotherapy was 73 and 89% in the nonmalignant and malignant groups, respectively. The engraftment, time to neutrophil, and platelet engraftment were not significantly different between the busulfan and the treosulfan cohorts. Rate of grade II-IV acute GvHD was significantly higher in the busulfan cohort than the treosulfan cohort (39% vs 15%; p = .016). No differences were observed in endothelial damage complications, chronic GvHD, relapse, overall survival, and transplant-related mortality. CONCLUSIONS: Busulfan-based conditioning regimens are used more frequently for children undergoing allogenic HSCT, but treosulfan-based conditioning is gaining acceptance. Treosulfan-based conditioning is associated with lower rates of acute GvHD, and no significant differences on overall survival were observed compared with busulfan.

Haploidentical hematopoietic stem cell transplantation in pediatric and adolescent patients: A study of the Spanish hematopoietic stem cell transplantation group (GETH).

INTRODUCTION: The main advantages of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) are the immediate availability of donors, the possibility of developing cell therapy approaches with different novel transplant platforms, and the procedure's cost savings. METHODOLOGY: We retrospectively analyzed the pediatric haplo-HSCT activity of the Spanish hematopoietic stem-cell transplantation group (GETH) between 1999 and 2016, aiming to study clinical characteristics and outcomes by describing patient groups with non-malignant disease (NMD) or malignant disease (MD) and the impact of 2 different periods (1999-2009 and 2010-2016) on long-term outcomes. RESULTS: Twelve centers performed 232 haplo-HSCTs in 227 children, representing 10% of all pediatric allogeneic HSCT activity in Spain from 1999 to 2016, with a notable increase since 2013. Most haplo-HSCTs (86.7%) were performed in patients with MD; 95% received peripheral blood stem cells from donors, and 78.9% received ex vivo T-cell depleted grafts. Non-manipulated grafts using post-transplantation cyclophosphamide have been incorporated since 2012. We observed a higher percentage of graft failure in NMD versus MD (32% vs. 15.6%; p=0.029). Relapse and transplant-related mortality were the procedure's main limitations in MD and NMD, respectively. Five-year overall survival was 48.5% (SE 3.9), with no statistically significant difference when comparing the MD and NMD cohorts. Patients who received previously a HSCT the overall survival was significantly decreased. We observed no survival improvement over time. CONCLUSIONS: Although haplo-HSCT is an increasingly employed treatment option, our patients' results need improvement. We need to develop reference centers, especially for NMD whose rarity makes it difficult to gain experience.

Actinomyces in the mediastinum. Surprise is key in all art.

Introduction: Actinomycosis is an unusual chronic granulomatous infectious disease. They are commensals in various sites of the human body but with little pathogenicity. Actinomyces israelii is the most prevalent species but more than 30 species have been described. Infection of the lower respiratory tract is unusual, the involvement of mediastinum being even rarer. Case report: A 63-year-old man, previously healthy and living in a rural area, presented with a 5-month history of hemoptysis, pleuritic pain, weight loss, and night sweats. Community-acquired pneumonia with a mediastinal mass was documented, for which he received antibiotic management. Thoracoscopy was carried out for diagnosis and resection of the mediastinal mass due to inconclusive findings in the percutaneous biopsy. Pathology reported the presence of filamentous Gram-positive bacteria visible in Grocott staining. Due to the pathology findings, and the fact that no other infectious agents were identified, a diagnosis of actinomycosis was established. Treatment with oral amoxicillin 1g TID for 6 months was initiated. Conclusions: As far as we are aware, we present the sixth case of mediastinal actinomycosis. We present this case to bring attention to this rare but clinically relevant presentation to be considered as a differential diagnosis of mediastinal masses and to emphasize the need for specific anaerobic cultures to improve the diagnostic yield.

Clinical and histopathological evaluation of 50 acantholytic cutaneous squamous cell carcinomas: Analysis outcome in a retrospective case-control study.

BACKGROUND: Acantholytic cutaneous squamous cell carcinomas (aCSCCs) have been classically considered as a high-risk variant of CSCC. However, more recent studies show that aCSCC does not confer more aggressiveness. This study aims to establish whether the prognosis of the aCSCC is worse than that of the non-acantholytic (naCSCC) or not. METHODS: Retrospective case-control study with 50 aCSCCs and 50 naCSCCs. For each aCSCC, an naCSCC with similar high-risk features to the aCSCC but with no acantholysis was selected. Prognosis between both groups was compared. RESULTS: The mean age was 86 years (SD 9.61). Sixty-one patients were men. Thirty-nine CSCCs were located in high-risk head and neck areas. Twenty CSCCs exhibited a poor degree of differentiation, and 36 showed an infiltrative growth pattern. The tumor diameter was 18.71 mm (interquartile range, IQR 35), and the tumor thickness was 6.72 mm (IQR 15.50). Twelve CSCCs exhibited perineural infiltration, and eight CSCCs exhibited invasion beyond the subcutaneous fat. Positive margins after excision of the tumor in 22 aCSCCs vs eight naCSCCs (P < 0.02). Nineteen poor-prognosis events were observed (local recurrence, lymph node metastasis, and death from CSCC). However, no differences were observed between both groups when comparing poor-prognosis events. CONCLUSION: The proportion of unfavorable events is similar in aCSCC and naCSCC. The acantholytic histopathological subtype is not associated with a poorer prognosis than the non-acantholytic CSCC in our cohort.

Experience of a Strategy Including CYP2C19 Preemptive Genotyping Followed by Therapeutic Drug Monitoring of Voriconazole in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation.

Many factors have been described to contribute to voriconazole (VCZ) interpatient variability in plasma concentrations, especially CYP2C19 genetic variability. In 2014, Hicks et al. presented data describing the correlation between VCZ plasma concentrations and CYP2C19 diplotypes in immunocompromised pediatric patients and utilized pharmacokinetic modeling to extrapolate a more suitable VCZ dose for each CYP2C19 diplotype. In 2017, in our hospital, a clinical protocol was developed for individualization of VCZ in immunocompromised patients based on preemptive genotyping of CYP2C19 and dosing proposed by Hicks et al., Clinical Pharmacogenetics Implementation Consortium (CPIC) clinical guidelines, and routine therapeutic drug monitoring (TDM). We made a retrospective review of a cohort of 28 immunocompromised pediatric patients receiving VCZ according to our protocol. CYP2C19 gene molecular analysis was preemptively performed using PharmArray®. Plasma trough concentrations were measured by immunoassay analysis until target concentrations (1-5.5 µg/ml) were reached. Sixteen patients (57.14%) achieved VCZ trough target concentrations in the first measure after the initial dose based on PGx. This figure is similar to estimations made by Hicks et al. in their simulation (60%). Subdividing by phenotype, our genotyping and TDM-combined strategy allow us to achieve target concentrations during treatment/prophylaxis in 90% of the CYP2C19 Normal Metabolizers (NM)/Intermediate Metabolizers (IM) and 100% of the Rapid Metabolizers (RM) and Ultrarapid Metabolizers (UM) of our cohort. We recommended modifications of the initial dose in 29% (n = 8) of the patients. In RM ≥12 years old, an increase of the initial dose resulted in 50% of these patients achieving target concentrations in the first measure after initial dose adjustment based only on PGx information. Our experience highlights the need to improve VCZ dose predictions in children and the potential of preemptive genotyping and TDM to this aim. We are conducting a multicenter, randomized clinical trial in patients with risk of aspergillosis in order to evaluate the effectiveness and efficiency of VCZ individualization: VORIGENIPHARM (EudraCT: 2019-000376-41).

Lemierre's syndrome by Bacillus circulans, Fusobacterium nucleatum and Staphylococcus aureus with involvement of the internal and external jugular vein.

INTRODUCTION: Lemierre's syndrome refers to the septic thrombophlebitis of the internal jugular vein, secondary to a pharyngeal infection. Although it mainly affects the internal jugular vein, isolated cases have been described of involvement of the external jugular vein. The main etiological agent is Fusobacterium necrophorum. CASE REPORT: A 27-year-old male, previously healthy, presented with a 7-day history of sore throat and fever. He was diagnosed with Lemierre's syndrome, coinfection by Bacillus circulans, F. nucleatum and Staphylococcus aureus with an atypical presentation due to the involvement of the external jugular vein and the internal jugular vein. CONCLUSIONS: As far as we are aware, we present the first case of Lemierre's syndrome with these characteristics.

Selective T-cell depletion targeting CD45RA as a novel approach for HLA-mismatched hematopoietic stem cell transplantation in pediatric nonmalignant hematological diseases.

Severe aplastic anemia and congenital amegakaryocytic thrombocytopenia are rare bone marrow failure syndromes. Treatment for aplastic anemia consists of hematopoietic stem cell transplantation (HSCT) from a matched sibling donor or immunosuppressant drugs if there is no donor available. Congenital amegakaryocytic thrombocytopenia is a rare autosomal recessive disease that causes bone marrow failure and has limited treatment options, except for transfusion support and HSCT. In the absence of a suitable matched sibling donor, matched-unrelated, haploidentical, or mismatched donors may be considered. A 2-step partial T-cell-depletion strategy can remove CD45RA+ naïve T cells responsible for graft-versus-host disease (GvHD) while preserving memory T cells. Five patients underwent transplantation using this strategy with rapid neutrophil and platelet recovery. Acute and chronic GvHD ≥ grade 2 appeared in two and one patient, respectively. No severe infections were observed before day + 100. A high (60%) incidence of transplant-associated microangiopathy was observed. Three patients (60%) remain alive, with a median follow-up of 881 (range 323-1248) days. CD45RA-depleted HSCT is a novel approach for patients lacking a suitable matched donor; however, further improvements are needed.

The role of early natural killer cell adoptive infusion before engraftment in protecting against human herpesvirus-6B encephalitis after naïve T-cell-depleted allogeneic stem cell transplantation.

BACKGROUND: Naïve T-cell-depleted grafts have been employed as an ex vivo T-cell depletion (TCD) platform to prevent graft-versus-host disease (GvHD) and improve immune reconstitution by providing rapid donor memory T-cell reconstitution after allogenic hematopoietic stem cell transplantation (allo-HSCT). CD45RA- memory T cells confer protection against viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus; however, reports have shown an unexpectedly high incidence of human herpesvirus (HHV)-6B encephalitis among pediatric allo-HSCT patients. METHODS: We report the first 18 consecutive allo-HSCT, 16 haplo-HSCT, and two human leukocyte antigen-matched related donors implanted with naïve TCD grafts. All donors were administered three cell products: first, a CD34+ stem cell product; second, a CD45RA+ TCD graft, followed by an adoptive natural killer (NK) cell infusion within 10 days after HSCT. The study's primary endpoint was the incidence of HHV-6B encephalitis. RESULTS: Engraftment was achieved in 94.5% of cases; 2-year overall survival, event-free survival, and GvHD/relapse-free survival were 87.2% (95% CI 78.6-95.8), 67.3% (95% CI 53.1-81.5), and 64% (95% CI 50.5-78.1), respectively. HHV-6B reactivation occurred in 7 of the haplo-HSCT patients, six of who received a cell infusion with an NK/CD4 ratio <2. None of the patients developed encephalitis. CONCLUSIONS: In this clinical study, we show that early adoptive NK cell infusion after a 45RA+ TCD allo-HSCT graft is safe and can prevent HHV-6B encephalitis. We recommend infusing adoptive NK cells after allo-HSCT using CD45RA+ TCD grafts.

Ruxolitinib for steroid-refractory graft versus host disease in pediatric HSCT: high response rate and manageable toxicity.

Ruxolitinib, a selective Janus Kinase (JAK) 1/2 inhibitor, is a promising treatment for the steroid-refractory graft-vs-host disease (GvHD) after hematopoietic stem cell transplantation (HSCT). Most studies have been performed in the adult population showing efficacy against GvHD. In this retrospective study, we evaluated the outcomes of 19 children who received ruxolitinib for refractory acute or chronic GvHD (cGvHD) after HSCT from two Pediatric Hemato-Oncology Departments in Spain between March 2017 and December 2018. Patients received a median number of 4 (IQR 2) previous lines of treatment before starting ruxolitinib. The overall response rate in acute GvHD (aGvHD) and cGvHD was 87% and 91%, respectively. Complete response (CR) was observed in 37% of aGvHD and 8.3% of cGvHD. Remarkably, 43% and 40% of patients with steroid-refractory gastrointestinal aGvHD and lung cGvHD achieved CR. During ruxolitinib treatment, there were 36%, 31%, and 10% infections caused by viruses, bacteria, and fungi, respectively. Overall, four patients interrupted ruxolitinib due to infectious complications, hematological, and liver toxicity. The 2-year overall survival was 71.9% (CI 95% 58.6-85.2). Our experience supports the use of ruxolitinib as an effective treatment for steroid-refractory acute and cGvHD in children with a moderate toxicity profile.

Burden of invasive pneumococcal disease (IPD) over a 10-year period in Bogotá, Colombia.

BACKGROUND: Invasive pneumococcal disease (IPD) is the leading cause of infectious death worldwide. This study aimed to describe the epidemiology of IPD and the impact of pneumococcal conjugate vaccine-10 (PCV-10) over a 10-year period in Bogotá, Colombia. METHODS: This was a laboratory-based surveillance study of Streptococcus pneumoniae isolated from patients with IPD from 82 hospitals over 10 years in Bogotá, Colombia. Data were compared between two periods: 2007-2011 (before the introduction of PCV-10) and 2012-2017 (after the introduction of PCV-10). RESULTS: In total, 1670 patients with IPD were included in the study between 2007 and 2017. Between 2007 and 2011, the most common serotypes were 14, 1, 6B, 6A and 3. Between 2012 and 2017, the most common serotypes were 19A, 3, 14 and 1. A decrease in the incidence of IPD, particularly in children aged 0-4 years, was noted after the introduction of PCV-10. Importantly, this reduction in incidence was not observed in patients aged ≥50 years. CONCLUSIONS: The IPD burden in Bogotá remained stable between 2007 and 2017. The incidence of IPD decreased in children but not in older adults. The introduction of PCV-10 led to a change in the most prevalent serotypes to serotypes that are not included in PCV-10.