Directed sibling donor cord blood donation in the Chilean Public Health System. / Donación dirigida de sangre de Cordón Umbilical de Hermano Compatible en el Sistema de Salud Público de Chile.

INTRODUCTION: Cord blood (CB) as a source of Hematopoietic Stem Cells for Transplantation (HSCT) is well established. Worldwide, nonetheless, less than 10% of the CB HSCTs are performed with a match sibling donor. Since 2004, the Chilean National Childhood Cancer Program (PINDA) net work, has established a CB directed donation program for HSCT. PATIENTS AND METHOD: An obser vational, descriptive and retrospective study was designed to assess the number and characteristics of the CB units collected in the program as well as the number, clinical characteristics and follow-up of the patients who received an HSCT from those CB units between January 2004 and October 2018. RESULTS: Sixty CB units have been collected; 55 of them with full records and stored. The median volume collected was 74.8 ml (30.0-170.8), the median number of total nucleated cells was 7.6 x 10e8 (2.0-21.1), and the median of CD34+ cells was 1.6 x 10e6 (0.2-11.6). Four high-risk leukemia patients received HSCT, all of them developed severe complications after transplantation and one patient died due to relapse. Those patients currently alive have a 100% Karnofsky/Lansky score. The median follow-up time was 8 years. CONCLUSION: The PINDA program has allowed 4 patients to be transplan ted who otherwise would not have had access to a donor. This directed donation program could be seen as a model for the development of a public cord blood bank in Chile.

Intravenous palivizumab in respiratory syncytial virus infection after hematopoietic stem cell transplant in children.

Respiratory syncytial virus (RSV) infection can cause lower respiratory tract disease and mortality in pediatric hematopoietic stem cell transplant (HSCT) recipients. We report two children who underwent HSCT and developed RSV infection simultaneously at the Bone Marrow Transplant Unit. The treatment with intravenous palivizumab was provided and sequential viral loads were measured in nasopharyngeal (NP) and whole blood samples. To our knowledge, this is the first report where RSV loads were measured in parallel (NP and blood), before and after palivizumab, in correlation with a favorable clinical outcome in both cases.

Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric patients: a single center experience.

Anti-thymocyte globulin (ATG) has become a standard in preventing GVHD in related and unrelated donor transplantation, but there is no consensus on the best administration schedule. The PARACHUTE trial reported excellent CD4 immune reconstitution (CD4 IR) using a dosing schedule based on the patient's weight and pre-conditioning absolute lymphocyte count (ALC). In 2015 we introduced the PARACHUTE dosing schedule for pediatric patients at our center. One hundred one patients were transplanted for malignant and non-malignant diseases. In this non-concurrent cohort CD4 IR+, defined by a single CD4 count >50/µL on day 90, was seen in 81% of patients. The incidence of grade II-IV and III to IV aGvHD was 26.6% and 15.3% and 5% for cGvHD with no severe cases. We found no difference in aGvHD between donor type and stem cell sources. Five-year EFS and OS were 77.5% and 83.5%. Grade III-IV GFRS was 75.2%. CD4 IR+ patients had better EFS (93.1% vs. 77.7%, p = 0.04) and lower non-relapse mortality (2.7% vs. 22.2%, p = 0.002). The PARACHUTE ATG dosing schedule individualized by weight and ALC results in good early immune reconstitution, low incidence of cGvHD, and favorable survival for patients with different disease groups, donor types, and stem cell sources.

[Mycobacterium tuberculosis infection in a pediatric patient who underwent a hematopoietic stem cell transplant]. / Infección por Mycobacterium tuberculosis en una niña sometida a trasplante de progenitores hematopoyéticos.

We report the case of a 10 year old girl with a relapsed acute lymphoblastic leukemia, who underwent a haploidentical hematopoietic stem cell transplant (HSCT), with grade II skin and digestive graft versus host disease, treated with corticosteroids and cyclosporine. On day + 54, she presented fever, with no other remarkable clinical findings. Imaging study showed the presence of lung and liver nodules, liver biopsy was performed. The study included histology, staining and culture for bacteria and fungi, and the preservation of a piece of tissue at -20°C for future prospective studies. Ziehl Nielsen stain was positive, and study for Mycobacterium infection was performed. Microbiological smears of tracheal and gastric aspirate, and bronchial fluid obtained by bronchoalveolar lavage (BAL) were positive. The final report confirmed Mycobacterium tuberculosis in gastric content, sputum, BAL and liver tissue, susceptible to rifampin, isoniazid, streptomycin and ethambutol, with determination of mutations for genes rpoß and kat G (-). Tuberculosis (TB) diagnosis was confirmed. The girl received daily therapy for two months and then she continued on three times per week therapy for 9 months. Controlled by the transplant, infectious diseases and respiratory teams, the patient remained in good general condition, with radiologic resolution of pulmonary and liver involvement and negative smears. We conclude that Mycobacterium tuberculosis infection should be part of differential diagnosis of febrile illness in patients undergoing HSCT, and biopsy should be a standard practice of early diagnosis in these patients.

Haploidentical stem cell transplantation for children with high-risk leukemia.

BACKGROUND: The Chilean population is ethnically diverse, and more than 50% of children referred for hematopoietic stem cell transplantation (HSCT) lack a suitable donor. PROCEDURE: To expand the donor pool, we assessed the feasibility, tolerance, and efficacy of using a haploidentical (HI) donor and a reduced-intensity conditioning regimen for high-risk pediatric leukemia. This study was facilitated by technology transfer from St. Jude Children's Research Hospital over the 2 preceding years. RESULTS: Between March 2006 and April 2009, 10 patients (median age, 9.8 years) received T cell-depleted grafts at Calvo Mackenna Hospital in Santiago. Median cell doses were CD34+: 7.45 × 10(6)/kg (range, 4.00-20.20 × 10(6)/kg); CD3+: 0.88 × 10(5)/kg (0.11-1.35 × 10(5)/kg); and CD56+: 71.30 × 10(6)/kg (31.50-131.80 × 10(6)/kg). Nine patients experienced complete engraftment; six of the nine remain alive and clinically well 13-50 months post-HSCT. Three patients died after bone marrow relapse, while only one died of transplant-related causes. Virus reactivation was the main post-transplant complication: 5/10 had positive CMV PCR but none had CMV disease. One patient developed acute GvHD > grade II and only one had chronic GvHD. CONCLUSIONS: HI-HSCT is feasible in our setting, offers a rational treatment option, and expands the donor pool significantly for children with high-risk leukemia in a developing country. This information is especially relevant to other ethnically diverse populations that are poorly represented in international donor registries.

[Prophylaxis against Epstein Barr disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation]. / Profilaxis de enfermedad por virus de Epstein Barr en niños y adultos receptores de trasplante de órganos sólidos y de precursores hematopoyéticos.

Post transplant lymphoproliferative disease (PTLD) associated with EBV infection is one of the most life-threatening complications in SOT and HSCT. Risk factors for infection or reactivation of EBV in SOT are the use of greater immunosuppression, seronegative receptor and CMV infection. In HSCT, the risk factors are related to type of transplant, HLA disparity, the greater immunosuppression, T-cell depletion and severe GVHD. There is no scientific evidence to support the use of specific therapy for prophylaxis of EBV infection. Prophylaxis recommendations focus on avoid exposure of transplant recipients to sources of virus, through hygiene practices such as hand washing (A3), avoid sharing utensils (B3) and avoid contact with potentially infected secretions (respiratory or saliva) (A2). For PTLD prevention, the recommendation is regular EBV viral load monitoring by rtPCR. In SOT with logarithmic rising of EBV loads, it is recommended to reduce immunosuppression and periodically perform exams to diagnose PTLD. In HSCT, it is recommended to reduce immunosuppression whenever possible, and use rituximab according to speciic protocol. Acyclovir or gancyclovir have not proven to be of any eficacy in PTLD prophylaxis in SOT (C3) or HSCT (D2), so their administration as preemptive therapy is no recommended.

[Prophylaxis against respiratory viral disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation]. / Profilaxis de infection por virus respiratorios en niños y adultos sometidos a trasplante de órganos sólidos y precursores hematopoyéticos.

Respiratory viruses have been identified as a cause of morbidity and mortality in patients undergoing SOT and HSCT, specially in children. The most frequent are respiratory syncytial virus (RSV), influenza (FLU), parainfluenza (PI) and adenovirus (ADV). These infections are associated with progression to severe lower respiratory tract infections in up to 60% of the cases. It is advised to apply universal protection recommendations for respiratory viruses (A2) and some specific measures for FLU and AD. FLU: Annual anti-influenza vaccination (from 4-6 months post-transplantation in SOT, 6 months in HSCT (A2)); post- exposure prophylaxis in FLU (oseltamivir for 10 days (B2)). In lung transplantion, the prophylaxis should last as long as the risk period (B2). ADV: There is no vaccine nor valid chemoprophylaxis strategy to prevent ADV disease. In some specific HSCT recipients, weekly PCR monitoring is recommended until day+100 (A3).

[Prophylaxis against Chagas disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation]. / Profilaxis de enfermedad de Chagas en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos.

Chagas disease is a zoonosis caused by T. cruzi. The estimated prevalence in endemic areas is 0.6-0.9 / 100,000. In immunocompromised behaves as an opportunistic pathogen highly aggressive and can evolve with meningoencephalitis, myocarditis or systemic disease. We recommend obtaining serology for all donor and recipient of SOT and HSCT. An infected donor should be discarded as such. In the case of D (-) R (+) exists controversy between prophylaxis and pre emptive therapy. The chosen drug for prophylaxis is nifurtimox for 3 months, effective but with relevant adverse effects. Monitoring should be done with RPC and MicroStrout weekly until six months post-transplant, then on a monthly basis for the duration of immunosuppression and continued for life clinical monitoring (C3).

[Prophylaxis against Toxoplasma gondii disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation]. / Profilaxis de toxoplasmosis en niños y adultos sometidos a trasplante de órganos sólidos y precursores hematopoyéticos.

Toxoplasmosis is a widely distributed zoonosis produced by the parasite T. gondii. In Chile the seroprevalence has been estimated between 20-37% in general population. Defined risk groups acquire or reactivate the infection by T. gondii in patients undergoing SOT and HSCT are: heart transplant or heart-lung with D (+) and R (-), allogeneic HSCT with R (+), HSCT with cord cells, GVHD, history of previous clinical toxoplasmosis and use of corticosteroids for prolonged periods or in high doses. Hand washing, hygiene in food handling and weekly post-transplant surveillance since day 15 post transplant for six months, are universally recommended. All patients with SOT and HSCT, regardless of risk, should receive prophylaxis with cotrimoxazole and require no another specific prophylaxis against T. gondii (A2). It is particularly important in high-risk patients who cannot receive cotrimoxazole prophylaxis establish specific alternative against T. gondii (B3).

[Ovarian reserve and premature ovarian failure in girls and adolescents after hematopoietic stem cell transplantation]. / Reserva ovárica y falla ovárica prematura en niñas y adolescentes postrasplante de progenitores hematopoyéticos.

INTRODUCTION: The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this procedure might have. OBJECTIVE: to measure ovarian function and reserve after SCT. PATIENTS AND METHOD: A descriptive, observatio nal, and cross-sectional study of girls and adolescents with SCT between 1999 and 2011. External gynecologic examination, hormone tests, and abdominal gynecologic ultrasound were performed, observing pubertal development pre-SCT. The following data from the clinical record were recorded: baseline pathology, type of conditioning, use of radiotherapy in conditioning, age at the time of SCT, and history of acute or chronic graft-versus-host disease (GVHD). Hormonal tests included follicle- stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin (PRL), thyroid-stimula ting hormone (TSH), free thyroxine, total testosterone, sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH). Statistical analysis included the chi-square or Fisher's Exact test with a p-value < 0.05. RESULTS: 41 patients were evaluated. The median age at the time of SCT was 6.8 years (1.5-14.1) and the median age at evaluation was 14.8 years (range: 4-25.4 years). 93% of the transplants were in patients with oncological disease and with myeloablative conditioning regimens. All patients presented decreased ovarian reserve, and 72% showed Premature Ovarian Failure (POF). CONCLUSIONS: All patients had decreased ovarian reserve and most of them had a high prevalence of POF. Before SCT, a gynecological evaluation and subsequent follow-up for hormone monitoring and initiation of hormone replacement are essential.

[Respiratory viral infections during episodes of fever in children undergoing hematopoietic stem cell transplantation]. / Infecciones respiratorias virales en episodios de fiebre en niños con trasplante de precursores hematopoyéticos.

BACKGROUND: Children undergoing hematopoietic stem cell transplant (HSCT) can develop respiratory viral infections (RVI) during fever episodes. There are few data about clinical outcomes in RVI and compared to bacterial infections (BI) in this population. AIM: To determine clinical outcome of RVI, compared to BI in children with HSCT. METHODS: Prospective study, patients ≤ 18 years with cancer and HSCT admitted with fever at a National Bone Marrow Transplant Center (Hospital Calvo Mackenna), Chile, (April-2016 to May-2019). Clinical assessment, laboratory tests, blood cultures, nasopharyngeal sample for multiplex-PCR (Filmarray®), viral loads by PCR and cytokine panel (Luminex®, 38 cytokines) were performed. The following outcomes were evaluated: upper/lower respiratory tract disease (RTD), admission to ICU, mechanical ventilation, mortality and antimicrobial withdrawal. RESULTS: Of 56 febrile episodes, 35 (63%) were RVI, 12 (21%) BI and 9 (16%) with unknown etiology (UE). Median of age was 8.5 years, 62% male gender. Rhinovirus (54%) and coronavirus (15%) were the more frequent detected viruses. No significant differences in cytokine levels were observed between RVI and BI. 94% of RVI patients had symptomatic RTD, versus 33% in BI and 33% in UE group (p < 0.001), with lower-RTD in 69% of RVI group (p < 0,001). Admission to ICU was 11% in RVI, 17% in BI and 11% in UE group (p = 0.88); only 2 patients required mechanical ventilation (p = 0.37) and no mortality was reported. After an RVI was detected by PCR, antimicrobials were withdrawal in 26% of patients with RVI (p: 0.04). CONCLUSION: RVI are frequent etiologic agents in febrile episodes of patients with HSCT. Viral detection might help to rationalize the use of antimicrobials in this population.

[Basic requirements of facilities for hospitals that treat hemato-oncological patients: hospital environment, diagnostic protocols and therapeutic arsenal]. / Parte I. Requerimientos básicos de infectología para hospitales que atienden pacientes hemato-oncológicos: ambiente hospitalario, protocolos diagnósticos y arsenal terapéutico. Fundamentación.

The care of cancer patients, including recipients of hematopoietic stem cell transplantation, has numerous challenges for hospitals that must provide safe environments in which exposure to pathogens that generate morbidity and mortality is reduced at maximum. At the same time, they must have established protocols that allow a rational study of the possible infectious etiologies and the existence of an adequate therapeutic arsenal together with timely treatment algorithms, updated according to consensus guidelines and effective according to the suspected or confirmed infection. This article introduces some of the arguments that support these requirements, then that are developed in three successive articles dedicated to the hospital environment, diagnostic protocols and therapeutic arsenal.

[Hospital environment variables that affect the risk of infections of cancer patients and recipients of hematopoietic precursor transplants: Design, care processes, microbiological quality of air and water]. / Parte II. Variables del ambiente hospitalario que inciden en el riesgo de infecciones de pacientes con cáncer y receptores de trasplante de precursores hematopoyéticos: Diseño, procesos asistenciales, calidad microbiológica del aire y agua.

The hospital environment is a potential source of exposure to pathogens such as bacteria, fungi and parasites that can cause infections in patients with cancer including transplanted hematopoietic precursors. To mitigate this risk, the design, construction and location elements of the patient care area must be taken into account. Recommendations are given to provide safe environments, including aspects related to characteristics and use of a protected environment, the definition of critical processes, clinical teams dedicated to the care of patients, suggestions of areas to be monitored, the microbiological quality of air and water.

[Evaluation of the prescription, consumption and costs of antifungal drugs in a pediatric hospital in Chile]. / Evaluación de la indicación, consumo y costos de antifúngicos en un hospital pediátrico de Chile.

BACKGROUND: The increase of invasive fungal disease (IFD) in immunocompromised patients has led to the frequent prescription of highly active antifungal drugs but with a high economic cost. AIM: To characterize the use of antifungals drugs, evaluate its prescription and determine consumption and associated costs. METHODS: Retrospective descriptive study from January 2015 to April 2016. Audit of prescriptions and review of clinical files. Each prescription was classified according to whether it corresponded to a possible, probable or proven invasive fungal disease (IFD). Consumptions and treatment costs were calculated. RESULTS: 152 antifungal prescriptions were audited in 79 patients. The total cost of antifungal medications was US $ 714,413. 52.1% of the expenditure (US $ 372,319) corresponded to indications in proven IFD, 10.7% (US $ 76,377) probable IFD, 0.8% (US $ 5,638) non-IFI, 12.2% (US $ 87,459) IFD possible and 1.5% (US $ 10,896) non-IFD and 22.6% (US $ 161,723) was prophylaxis. The highest consumption was in indications related to IFD tested with a proven DOT of 10.54 days, with liposomal amphotericin B and iv voriconazole the drugs with the highest consumption with a DOT probable_AnBL of 3.15 and DOT proven voriconazole iv of 3.01. CONCLUSIONS: The consumption of antifungal drug medications generates high costs at 12% of the total pharmacy budget of our institution. The expense was associated mainly with the indications in IFI tested the voriconazole and amphotericin B liposomal with the highest consumption which added to its high cost and prolonged days of general therapy a big impact in the budget.

[Pharmacokinetics of posaconazol in the prophylaxis and treatment of invasive fungal infection in immunocompromised children in a pediatric hospital]. / Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico.

Background There is no consensus on the optimal dosage use of posaconazole (PSC) for invasive fungal infection (IFI) in pediatric patients and normally it is adjusted with drug levels (DLs) ≥ 0.7 µg/ml and ≥ 1.25 µg/ml for prophylaxis and treatment, respectively. Objective To describe the experience of monitoring DLs of PSC in immunocompromised pediatric patients with IFI and to determine if the recommended doses reach CP effective in prophylaxis (≥ 0.7 µg/mL) and treatment (≥ 1.25 µg/mL). Method A retrospective analysis in children who received PSC from January 2012 to October 2016, in the Oncology and Bone Marrow Transplant units at Hospital Calvo Mackenna was done Six patients with 78 DLs were reviewed (4 prophylaxis and 4 treatment). Median PSC dose was 12.5 and 18.8 mg/kg/d for prophylaxis and treatment, resulting in mean DLs of 0.97 and 1.8 µg/mL respectively. In prophylaxis 40/67 (60%) were recorded with DLs ≥ 0.70 µg/mL receiving a median dose of 12.5 mg/kg/d. While for treatment: 5/11 (46%) presented DLs ≥ 1.25 µg/mL, receiving a median dose of 18 mg/kg/d. Conclusion Our results are in line with the recommended for PSC dosage, but individualized monitoring is required to maintain adequate DLs.

[Drug interaction of voriconazole-cyclosporine in children undergoing hematopoietic stem cell transplantation (2013-2014)]. / Evaluación de interacción medicamentosa de voriconazol-ciclosporina en pacientes pediátricos que reciben trasplante de precursores hematopoyéticos (2013-2014).

BACKGROUND: Drug interactions (DI) in patients receiving hematopoietic stem cell transplantation (HSCT) are common and clinically significant, highlighting: anticonvulsants, voriconazole (VCZ) and cyclosporine (CsA), which require monitoring. OBJECTIVE: To describe the interactions between CsA-VCZ in children undergoing HSCT. METHODS: Retrospective, descriptive study in immunocompromised children hospitalized since January 2013 to December 2014 at Bone Marrow Transplant Unit, Hospital Dr. Luis Calvo Mackenna, who received CsA and VCZ. RESULTS: The median age was 5 years (3-6) and the median weight was 20 kg (17-30). Sixtythree baseline drug levels were analyzed, of those, 27 were CsA drug levels obtained previous to using VCZ and 36 were CsA drug levels collected concomitantly with VCZ. In the group CsA previous to VCZ, the CsA dose was 4.6 ± 2.6 (mg/ kg/ day) and the CsA average level was 188.8 ± 84.1 (µg/ml). In the group of CsA concomitantly with VCZ, the dose of CsA was 5.5 ± 3.0 (mg/ kg/day) (p = 0.07) and CsA average level was significantly higher: 232.5 ± 106.7 (µg/ml) (p = 0.04). CONCLUSION: This study shows an increased level of CsA when it is used together with VCZ. Therapeutic drug monitoring could improve the management of the DI and optimize the co-administration of CsA and VCZ.

[Analysis of voriconazole serum concentrations and safety profile in pediatric oncology patients]. / Análisis de concentraciones plasmáticas de voriconazol y su perfil de seguridad en pacientes oncológicos pediátricos.

BACKGROUND: Voriconazole (VCZ) serum drug levels (SDL) vary widely and are associated with increased mortality when they are below the therapeutic range for invasive aspergillosis (IA). AIM: To describe VCZ SDL in oncology pediatric patients in order to reach adequate concentrations for prophylaxis (≥ 0.5 mg/L) and treatment (≥ 1.0 y 2.0 mg/L) for IA and their relationship with toxicity. PATIENTS AND METHODS: Retrospective analysis of VCZ SDL and toxicities recorded in oncology pediatric patients between February 2013 and November 2014. The daily dosage and SDLs were analyzed according to administration route: intravenous (IV) and oral (PO), type of therapy (prophylaxis and treatment) and patient age (< 12 y ≥ 12 years old). RESULTS: 112 through levels from 26 patients were analyzed and the average age was 9.3 years-old. The SDL obtained from the IV route were 43.7%. There were more SDL ≥ 0.5 mg/L and ≥ 1.0 mg/L with the IV route than the PO route (p < 0.05). Patients younger than 12-years-old received a higher dosage than those ≥ 12 years old (median 18.6 and 9.2 mg/kg/d, respectively, p < 0.05). To reach SDL ≥ 0,5 mg/L with the PO route, a dosage of 200 mg every 12 hours showed the best results for all patients (80-100% SDL ≥ 0.5 mg/L). With an IV dosage between 14 and 20 mg/kg/day in patients > 12-years-old, 80% of the SDL were ≥ 1 mg/L and ≥ 2 mg/L. In patients younger than 12-year-old, dosages between 8-30 mg/ kg/day showed similar results (50-63% of SDL ≥ 1 mg/L and 36-40% of SDL ≥ 2 mg/L). Eight patients (30.8%) presented an adverse drug reaction and no relationship with the SDL was found. Conclusión: A VCZ standard dosage of 200 mg every 12 hours PO showed the best results for IA prophylaxis in all patients. Patients younger than 12-years-old would require higher dosages than the doses used in this study to attain adequate SDL for IA treatment. No relation with SDL and adverse reactions was found.

Donación dirigida de sangre de Cordón Umbilical de Hermano Compatible en el Sistema de Salud Público de Chile / Directed sibling donor cord blood donation in the Chilean Public Health System

Resumen: Introducción: La sangre de cordón umbilical (SCU) como fuente para trasplante de células proge- nitoras hematopoyéticas (TPH) está bien establecida. Internacionalmente, menos del 10% de los TPH de SCU corresponde a donantes hermanos compatibles. Dentro de la red del Programa Infantil Nacional de Drogas Antineoplásicas (PINDA), existe desde enero 2004 un programa de donación dirigida de SCU para TPH. Pacientes y Método: Se diseñó un estudio observacional, retrospectivo, descriptivo, se revisaron el número y características de las unidades de SCU recolectadas en el PINDA y el número, características y evolución de los pacientes trasplantados con esas unidades entre enero de 2004 y octubre de 2018. Resultados: Sesenta unidades de SCU han sido recolectadas, de ellas 55 con registro completo. La mediana de volumen de las unidades almacenadas fue 74,8 ml (30,0-170,8), la mediana de células nucleadas totales 7,6 x 10e8 (2,0-21,1), mediana de células CD34+ 1,6 x 10e6 (0,2-11,6). Cuatro pacientes con leucemias de alto riesgo fueron trasplantados; mediana de segui miento es de 8 años. Todos desarrollaron complicaciones severas post TPH, uno de ellos falleció de recaída y los tres actualmente vivos presentan un Karnofsky/Lansky 100%. Conclusión: El programa ha permitido el trasplante de 4 pacientes que de otro modo no habrían tenido acceso a un donante. Este programa de donación dirigida puede ser considerado una primera etapa para el desarrollo de un banco público de sangre de cordón umbilical en Chile.

Abstract: Introduction: Cord blood (CB) as a source of Hematopoietic Stem Cells for Transplantation (HSCT) is well established. Worldwide, nonetheless, less than 10% of the CB HSCTs are performed with a match sibling donor. Since 2004, the Chilean National Childhood Cancer Program (PINDA) net work, has established a CB directed donation program for HSCT. Patients and Method: An obser vational, descriptive and retrospective study was designed to assess the number and characteristics of the CB units collected in the program as well as the number, clinical characteristics and follow-up of the patients who received an HSCT from those CB units between January 2004 and October 2018. Results: Sixty CB units have been collected; 55 of them with full records and stored. The median volume collected was 74.8 ml (30.0-170.8), the median number of total nucleated cells was 7.6 x 10e8 (2.0-21.1), and the median of CD34+ cells was 1.6 x 10e6 (0.2-11.6). Four high-risk leukemia patients received HSCT, all of them developed severe complications after transplantation and one patient died due to relapse. Those patients currently alive have a 100% Karnofsky/Lansky score. The median follow-up time was 8 years. Conclusion: The PINDA program has allowed 4 patients to be transplan ted who otherwise would not have had access to a donor. This directed donation program could be seen as a model for the development of a public cord blood bank in Chile.

Infecciones respiratorias virales en episodios de fiebre en niños con trasplante de precursores hematopoyéticos / Respiratory viral infections during episodes of fever in children undergoing hematopoietic stem cell transplantation

Resumen Introducción: Los niños que reciben trasplante de precursores hematopoyéticos (TPH) pueden presentar infecciones respiratorias virales (IRV) durante episodios febriles. Los datos sobre su evolución clínica son escasos, así como la comparación de ellos con infecciones bacterianas (IB). Objetivo: Caracterizar la evolución clínica de pacientes con IRV, en comparación con IB en niños con TPH, cursando un episodio febril. Método: Estudio prospectivo en pacientes ≤ 18 años con cáncer y TPH ingresados por fiebre en el Hospital Luis Calvo Mackenna (2016-2019). Se realizó evaluación clínica y de laboratorio: hemocultivos, RPC para patógenos respiratorios (Filmarray®), cuantificación viral y medición de citoquinas en muestra nasal (Luminex®, 38 citoquinas). Se compararon los grupos IRV, IB y los de etiología no precisada (ENP) en relación con: infección respiratoria aguda (IRA), citoquinas nasales, ingreso a UCI, necesidad de ventilación mecánica, mortalidad y suspensión de antimicrobianos. Resultados: De 56 episodios febriles, 35 fueron IRV, 12 IB y 9 de ENP. Mediana de edad fue 8,5 años, 62% masculino. Un 94% de los casos IRV presentó IRA sintomática, versus 33% en los grupos IB y ENP (p < 0,001), con IRA baja en 69% de las IRV (p < 0,001). Rinovirus (54%) y coronavirus (15%) fueron las etiologías más frecuentemente detectadas. No hubo diferencias en citoquinas nasales entre los grupos IRV e IB. Ingreso a UCI: 11% del grupo IRV, 17% de IB y 11% de ENP (p = 0,88). Requirieron ventilación mecánica sólo 2 pacientes (p = 0,37) sin fallecimiento. Tras la detección viral respiratoria por RPC, se suspendió antimicrobianos en 26% de los casos con IRV (p = 0,04). Conclusión: Las IRV son frecuentes en niños con TPH y episodios febriles. La detección viral podría optimizar y racionalizar el uso de antimicrobianos en esta población.

Abstract Background: Children undergoing hematopoietic stem cell transplant (HSCT) can develop respiratory viral infections (RVI) during fever episodes. There are few data about clinical outcomes in RVI and compared to bacterial infections (BI) in this population. Aim: To determine clinical outcome of RVI, compared to BI in children with HSCT. Methods: Prospective study, patients ≤ 18 years with cancer and HSCT admitted with fever at a National Bone Marrow Transplant Center (Hospital Calvo Mackenna), Chile, (April-2016 to May-2019). Clinical assessment, laboratory tests, blood cultures, nasopharyngeal sample for multiplex-PCR (Filmarray®), viral loads by PCR and cytokine panel (Luminex®, 38 cytokines) were performed. The following outcomes were evaluated: upper/lower respiratory tract disease (RTD), admission to ICU, mechanical ventilation, mortality and antimicrobial withdrawal. Results: Of 56 febrile episodes, 35 (63%) were RVI, 12 (21%) BI and 9 (16%) with unknown etiology (UE). Median of age was 8.5 years, 62% male gender. Rhinovirus (54%) and coronavirus (15%) were the more frequent detected viruses. No significant differences in cytokine levels were observed between RVI and BI. 94% of RVI patients had symptomatic RTD, versus 33% in BI and 33% in UE group (p < 0.001), with lower-RTD in 69% of RVI group (p < 0,001). Admission to ICU was 11% in RVI, 17% in BI and 11% in UE group (p = 0.88); only 2 patients required mechanical ventilation (p = 0.37) and no mortality was reported. After an RVI was detected by PCR, antimicrobials were withdrawal in 26% of patients with RVI (p: 0.04). Conclusion: RVI are frequent etiologic agents in febrile episodes of patients with HSCT. Viral detection might help to rationalize the use of antimicrobials in this population.

Parte I. Requerimientos básicos de infectología para hospitales que atienden pacientes hemato-oncológicos: ambiente hospitalario, protocolos diagnósticos y arsenal terapéutico. Fundamentación / Basic requirements of facilities for hospitals that treat hemato-oncological patients: hospital environment, diagnostic protocols and therapeutic arsenal

Resumen La atención de pacientes con cáncer, incluyendo los receptores de trasplantes de precursores hematopoyéticos, plantea numerosos desafíos para los hospitales que deben proveer ambientes seguros, en que se logre aminorar al máximo posible la exposición a patógenos que generan morbilidad y mortalidad. Al mismo tiempo deben contar con protocolos establecidos que permitan realizar un estudio racional de las posibles etiologías infecciosas que pueden presentar estos pacientes. A su vez, deben asegurar la existencia de un arsenal terapéutico adecuado, junto a algoritmos de tratamiento oportuno, actualizado según guías consensuadas y efectivo según la infección sospechada o confirmada. En este artículo se introducen algunos de los argumentos que sustentan estos requerimientos que luego se desarrollan en tres artículos sucesivos dedicados al ambiente hospitalario, protocolos diagnósticos y arsenal terapéutico.

The care of cancer patients, including recipients of hematopoietic stem cell transplantation, has numerous challenges for hospitals that must provide safe environments in which exposure to pathogens that generate morbidity and mortality is reduced at maximum. At the same time, they must have established protocols that allow a rational study of the possible infectious etiologies and the existence of an adequate therapeutic arsenal together with timely treatment algorithms, updated according to consensus guidelines and effective according to the suspected or confirmed infection. This article introduces some of the arguments that support these requirements, then that are developed in three successive articles dedicated to the hospital environment, diagnostic protocols and therapeutic arsenal.