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The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year.Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners.Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability.Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.

Voriconazole is the antifungal of choice for the treatment of invasive aspergillosis (IA). Plasma concentrations (PCs)1 μg / mL llave been associated with better therapeutic results which have not always been achieved during treatment in immunocompromised children. In the necessity to initiate early and effective therapy for the infection, it is relevant to establish the voriconazole administration regimen that is associated with optimal PCs in this population.To compare the PC and safety of intravenous (IV) voriconazole, dosed BID and TID in immunocompromised children with indication of antifungal treatment.Retrospective observational study since January 2015 until July 2018 in a highly complex pediatric hospital in Santiago of Chile, in patients aged 0 to 17 years who received treatment with IV voriconazole. Those with renal replacement therapy, liver failure and / or renal failure were excluded. Trough PCs were compared between a group with BID dosing regimen versus another group with TID administration. Adverse reactions were evaluated in both groups.137 trough PCs were obtained in 76 children, with a median age of 9 years (0-17 years) in the BID group and 9 years (0-16) in the TID group with a median weight of 27 kg (6-83 kg) and 28 kg (9.3-60 kg), respectively. Patients12 years old exposed to TID dosages are 4.65 times (OR: 4.65, 95% CI 1.93-11.2) more likely to have PC1 gg/mL compared to BID administration (p = 0.001). Eight adverse reactions were reported, mainly photophobia, with no significant difference found between the BID and TID groups.TID dosages are associated with a greater probability of obtaining adequate exposure to voriconazole in patients12 years old compared to BID dosages, with a low frequency of adverse reactions.

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age &lt, 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations.

Hematopoietic cells transplants are technically complex and expensive imposing a huge burden on health care systems, especially those in developing countries and regions. In 2017 > 4500 transplants were done in 13 Latin American countries with established transplant programmes. We interrogated data on transplant rate, cost, funding source, hospital type, Gini coefficient and the United Nations Development Programme Inequality-Adjusted Human Development Index to determine co-variates associated with transplant development. Transplant rates varied almost 30-fold between the 13 countries from 345 in Uruguay to 12 in Venezuela with a regional transplant rate 7–8-fold lower compared with the US and EU. We found significant correlations between higher transplant cost, public funding, transplants in private hospitals with transplant rate. Low cost per transplant regardless of payor and transplants done in public hospitals were associated with low transplant rates. In contrast, high cost per transplant funded by the government and transplants done in private hospitals were associated with high transplant rates. Surprisingly, we found transplant rates were higher when transplants cost more, when they were done in private for-profit hospitals and payed for with public funds. These data give insights how to increase transplant rates in Latin America and other developing regions.

Resumen Introducción: El incremento de la enfermedad fúngica invasora (EFI) en pacientes inmunocomprometidos ha conducido a la frecuente prescripción de fármacos altamente activos pero de elevado costo económico. Objetivo: Caracterizar el uso de antifúngicos, evaluar su indicación y determinar consumo y costos asociados. Métodos: Estudio descriptivo, retrospectivo, desde enero de 2015 a abril de 2016. Auditoría de prescripciones y revisión de fichas clínicas; cada prescripción se clasificó de acuerdo a si correspondía a una EFI posible, probable o probada. Se calcularon consumos y costos de tratamientos. Resultados: Se auditaron 152 prescripciones de antifúngicos en 79 pacientes. El costo total de los medicamentos antifúngicos fue de US$ 714.413. El 52,1% del gasto (US $ 372.319) correspondió a indicaciones en EFI probada, 10,7% (US $ 76.377) EFI probable, 0.8% (US $ 5.638) no-EFI, 12,2% (US $ 87.459) EFI posibles y 1,5% (US $ 10.896) EFI descartada y 22,6% (US$ 161.723) fue profilaxis. El mayor consumo fue en indicaciones relacionadas a EFI probada con un DOT probada de 10,54 días, siendo anfotericina B liposomal y voriconazol iv los fármacos con mayor consumo con un DOTprobada AnBL de 3,15 y DOT probada voriconazol iv de 3,01. Conclusiones: El consumo de medicamentos antifúngicos genera altos costos correspondiente al 12% del presupuesto total de farmacia de nuestra institución. El gasto se asoció principalmente a indicaciones en EFI probadas, voriconazol y anfotericina B liposomal los con mayor consumo, lo que sumado a su alto costo y días prolongados de terapia generan un gran impacto en el presupuesto.

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.

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.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.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.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.

Patients with Primary Immunodeficiencies (PID) are at a higher risk of developing severe morbidities and mortality due to the administration of BCG vaccine. Risk-to-benefit of universal BCG vaccina tion of newborns must be assessed periodically. Chile has a low incidence of tuberculosis (TB) but the local epidemiology has recently changed with an increase of TB cases. Changes in the BCG vaccine schedule have been made in countries with similar or higher TB incidences and lower BCG vaccine coverage, with no increase in the severe TB cases, which are prevented by BCG. These changes have prevented serious complications in PID patients. We propose a critical analysis of the BCG adminis tration date in Chile due to the technical possibility of performing neonatal PID screening.

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.

The book called “A uterus is the size of a fist” by Angélica Freitas was released in 2012 and still is one of the most relevant contemporary poetry work by a female author, mainly because it anticipated the diffusion of subjects related to the third wave of feminism in which we live now. From a selected group of poems in this book, the present article explores the feminine stereotypes in its nuances and develops reflections on how patriarchy values imposed on the “woman-body” —a termcoined by Paul B. Preciado —influence on its autonomy, whether byspecifying beautystandards or byadopting a moral that regulates women behavior. For this purpose, the analysis’ theoretical support relies on Simone de Beauvoir and Naomi Wolf’s considerations in attempt to establisha dialogue between its specific temporalities converging onto the situation of women in today's society. O livro Um Útero é do Tamanho de um Punho, de Angélica Freitas, foi lançado em 2012 e permanece sendo uma das obras de poesia contemporânea de autoria feminina mais relevantes dos últimos anos, principalmente por ter antecipado a difusão de temas associados à terceira onda feminista que estamos vivendo. A partir de poemas selecionados do livro, o presente artigo se propõe a explorar as nuances dos estereótipos femininos e desenvolver reflexões acerca da maneira como os valores patriarcais da ditadura da beleza impostos ao corpo-mulher — nomenclatura designada por Paul B. Preciado—influenciam na autonomia deste, seja por estipular critérios de uma ordem estética, seja pela adoção de uma moral reguladora de condutas. Para tanto,o suporte teórico desta análise contará particularmente com as ponderações de Simone de Beauvoir e Naomi Wolf na tentativa de estabelecer um diálogo entre as temporalidades específicas dos estudos de cada uma delas convergindo sobre a atual situação da mulher na sociedade.

Resumen Introducción En pediatría no existe consenso en la dosificación de posaconazol (PSC) para profilaxis y tratamiento de la infección fúngica invasora (IFI), usándose la medición de concentraciones plasmáticas (CPs) del fármaco. Objetivo Describir la experiencia de monitoreo de las CPs de PSC en niños inmunocomprometidos con IFI y determinar si las dosis recomendadas alcanzan CPs efectivas en profilaxis (≥ 0,7 µg/mL) y tratamiento (≥ 1,25 µg/mL). Método Análisis retrospectivo en niños que recibieron PSC suspensión como profilaxis o tratamiento entre enero de 2012 y octubre de 2016, en las unidades de Oncología y Trasplante de Médula Ósea del Hospital Calvo Mackenna. Resultados 78 CPs en seis pacientes (4 indicaciones de profilaxis y 4 tratamientos) fueron revisados. La mediana de dosis de PSC fue de 12,5 y 18,8 mg/kg/d para profilaxis y tratamiento, respectivamente, resultando CP mediana de 0,97 y 1,8 μg/mL, respectivamente. En profilaxis, se registraron 40/67 (60%) con CP ≥ 0,70 μg/mL recibiendo una mediana de dosis de 12,5 mg/kg/d. Mientras que para el tratamiento: 5/11 (46%), presentaron CP ≥ 1,25 μg/mL, recibiendo una mediana de dosis de 18 mg/kg/d. Conclusión Nuestros resultados se ajustan a lo recomendado para la dosificación de PSC, pero evidencian una necesidad de realizar una monitorización individualizada para mantener adecuadas CPs.

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.To characterize the use of antifungals drugs, evaluate its prescription and determine consumption and associated costs.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.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.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.

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.

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009-2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11 519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5-8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3-4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.

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.To describe the interactions between CsA-VCZ in children undergoing HSCT.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.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).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.

Background To determine the prevalence, characteristics, and risk factors associated with metabolic syndrome (MS) in patients undergoing hematopoietic stem cell transplantation (HSCT) in the Chilean National Program. Procedures Descriptive and cross-sectional study including 69 patients was conducted. Body mass index, pubertal development, waist circumference, arterial pressure (AP), and triglycerides, HDL-cholesterol, and glucose levels were recorded at the time of study entry. The National Cholesterol Education Program (Adult Treatment Panel III, as modified by the American Heart Association) criteria are often used to diagnose MS in adults; however, for children and adolescents we followed criteria according to De Ferranti and American Diabetes Association. Statistical analyses were performed with a chi-square test or Fisher's exact test according to sample size. Results Sixty-nine patients were studied. The median age at the time of diagnosis was 12.9 years, and the median time of follow-up post-transplant was 4 years. Forty-three patients were males, 54 patients had malignant diseases, and 59 patients received allogeneic transplants. Of the 69 patients, 32% had MS; the most common MS features were abdominal obesity (73%), hypertriglyceridemia (91%), and a low HDL-cholesterol level (96%). The most significant risk factor for MS was corticosteroid therapy use pre- (P

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 × 106/kg (range, 4.00–20.20 × 106/kg); CD3+: 0.88 × 105/kg (0.11–1.35 × 105/kg); and CD56+: 71.30 × 106/kg (31.50–131.80 × 106/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. Pediatr Blood Cancer 2012; 59: 895–901. © 2012 Wiley Periodicals, Inc.

Background Cytomegalovirus (CMV) infection remains as an important cause of morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). Our aim was to assess the incidence, risk factors, and outcome related to CMV infection in children after HSCT in a developing country. Methods From October 1, 1999, to December 31, 2005, we prospectively studied all patients admitted to the HSCT unit at Hospital Luis Calvo Mackenna in Santiago, Chile. Serologic studies before transplantation and weekly CMV infection surveillance (antigenemia or quantitative PCR) were routinely obtained. Patients with positive antigenemia or quantitative PCR received pre-emptive therapy with ganciclovir, and cases of unfavorable clinical evolution, persistent positive antigenemia, or quantitative PCR after 14 days of ganciclovir were treated with foscarnet. Results Ninety-seven patients received HSCT. Their median age was 8 years (range, 3 months to 24 years) and their overall survival was 67%. CMV reactivation was diagnosed in 26 patients. Of these, three developed CMV disease (two interstitial pneumonia, one hemorrhagic cystitis). One of the patients with pneumonia died. Risk factors identified were pre-transplant serologic status (positive recipient), acute and chronic graft versus host disease (GvHD), GvHD prophylaxis, and treatment with antithymocyte globulin. Conclusions The rate and prognosis of CMV infection among children treated at our HSCT unit is similar to those reported from industrialized countries. These findings reflect adequate prevention and management of CMV infection within our program. Pediatr Blood Cancer 2009;53:453–458. © 2009 Wiley-Liss, Inc.

Correction to: Bone Marrow Transplantation (2017) 52, 671–677; doi:10.1038/bmt.2016.361; published online 23 January 2017 Since the online publication of this article, the authors realised there were errors in the legends for Figures 1 and 2. The original legend for Figure 1 was: ‘Reasons for auto (left) (N=2057) and allotransplants (right) (N=1206).

Hematopoietic stem cell transplant (HSCT) is a treatment option in many otherwise deadly conditions, but its development is a great challenge in limited resourced countries. These countries represent a heterogeneous group with widely different problems, so each new HSCT program must develop its own project on its particular settings. Before any HSCT program is envisaged a preestablished treatment protocol within a network to assure opportunity should be established including a referral center network with adequate first line treatment. A broad participative HSCT committee will lead to local sensible HSCT indications and transparent priorization of patients.

Se presenta el caso clínico de una niña de 10 años, con una leucemia linfoblástica aguda en recaída, sometida a un trasplante de progenitores hematopoyéticos (TPH) haploidéntico, con enfermedad injerto contra hospedero cutánea y digestiva grado II, en tratamiento con corti-costeroides y ciclosporina, que presentó el día +54 posttrasplante fiebre y compromiso de estado general. Dentro del estudio de su cuadro febril se practicaron imágenes que mostraron presencia de nódulos pulmonares y hepáticos. Se realizó una biopsia hepática cuyo estudio incluyó histología, tinciones y cultivo para bacterias y hongos. La tinción de Ziehl Nielsen de tejido hepático, así como las baciloscopias de contenido gástrico, aspirado traqueal y de fluido bronquial obtenido por lavado broncoalveolar (LBA) fueron positivas. El informe definitivo de cultivo confirmó Mycobacterium tuberculosis en contenido gástrico, esputo, LBA y tejido hepático, sensible a rifampicina, isoniazida, estreptomicina y etambutol, con determinación de mutaciones de genes rpoβ y kat G (-). Se confirmó el diagnóstico de tuberculosis, por lo que recibió tratamiento diario con cuatro fármacos por dos meses y luego terapia trisemanal con rifampicina, isoniazida y etambutol por nueve meses. Controlada por los equipos de trasplante, infectología y broncopulmonar, la paciente se mantiene actualmente en buenas condiciones generales, con imágenes con resolución del compromiso hepático y pulmonar y baciloscopias negativas. La infección por M. tuberculosis debe formar parte del diagnóstico diferencial de los cuadros febriles en los pacientes sometidos a TPH, y la toma de biopsia debe ser una práctica habitual y precoz en el enfrentamiento diagnóstico de estos pacientes.

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 rpoβ 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.

More than a million HCT have been performed worldwide to date, but transplant rates and indications vary widely across regions. The Latin American Bone Marrow Transplantation Group (LABMT) was created under the auspices of the Worldwide Network for Blood and Marrow Transplantation (WBMT) in 2011 to assist in diffusing the practice, to integrate centers from multiple countries and to improve access to transplantation in the region. To evaluate the actual HCT activity, trends and contemporary practices in Latin America (LA), the LABMT surveyed centers for the annual activity from 2009 to 2012. Methods: The WBMT Global Activity Survey was used as a template and sent to all Hematology and HCT Societies in the region. This survey includes information of annual HCT numbers by center, indications, stem cell source and donor type. Results: A total of 11,116 HCT were performed between 2009 and 2012 with an increase in annual numbers from 2,517 in 2009 to 3,072 in 2012 (22%). The majority of the HCT were autologous (62%) with a 32% increase in activity over the period analyzed. In contrast, the increase in allogeneic HCT (6%) was relatively small. The majority of allogeneic HCT used related donors (n=3210), mostly HLA-identical peripheral blood (n=1812), bone marrow (n=1128) and non-identical related peripheral blood (n=156). Unrelated donor HCT (n=982) were performed mostly using cord blood (n=427), followed by bone marrow (n=332) and peripheral blood (n=223). In 2012, 91 teams from 12 countries reported 3,072 patients. Transplant rates (TR; HCT/10 million population) were 21 for allogeneic (ranging from 6 in Venezuela to 85 in Uruguay) and 60 for autologous HCT (ranging from 8 in Mexico to 215 in Uruguay). Unrelated donor TR was 5, ranging from 0 (Costa Rica, Panama, Peru, Paraguay and Venezuela) to 18 (Chile). Transplant center team density (team/10 million inhabitants) was 1.8 in 2012, with the highest in Uruguay (15), followed by Panama (8), Costa Rica (4), and Argentina (4). In comparison to other regions, transplant center density in LA was identical to the Asian Pacific region and lower than in Europe (7) or US/Canada (6). TR in LA compared to Asia/Pacific were higher for autologous (39 vs. 14) and lower for allogeneic (21 vs. 24, respectively, Table 1). Most transplant indications for autologous HCT (65% of all HCT) were plasma cell disorders (48%) and lymphomas (41%). Most allogeneic transplants (35% of all HCT) were performed for acute leukemias (58%, equally myeloid and lymphoid leukemias) and 18% for non-malignant disorders. Conclusion: While transplant indications are comparable to HCT performed in Europe and North America, transplant rates, transplant center and transplant team densities in LA are markedly lower. More autologous than allogeneic HCT are performed and autologous HCT increased considerably between 2009 and 2012. Unrelated donor TR is lower than in other regions. Initiatives are currently being taken to increase transplant activity, especially using alternative donor transplants within the region. Table 1. Transplant Rates and Team Density Worldwide Transplant rates (HCT/10 million population) Team density Region POP TOTAL AUTO ALLO FAMILY SIBLING UNRELATED LA 511.7 60.0 39.2 20.9 16.0 14.3 4.9 1.8 SEAR/WPR 3078.0 38.6 14.2 24.4 12.5 8.2 11.9 1.8 EUROPE 846.4 379.3 222.5 156.8 68.2 57.0 88.6 7.6 USA/Canada 348.0 482.5 264.9 217.5 91.2 75.8 126.3 6.2 EMR/AFR 690.9 29.8 12.7 17.2 15.7 15.0 1.4 0.4 HCT, hematopoietic cell transplantation; POP, population; AUTO, autologous; ALLO, allogeneic; SEAR/WPR, South East Asia/Western Pacific Region; LA, Latin America; EMR/AFR; Eastern Mediterranean/African Region Disclosures No relevant conflicts of interest to declare.

Cytomegalovirus (CMV) infection remains as an important cause of morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). Our aim was to assess the incidence, risk factors, and outcome related to CMV infection in children after HSCT in a developing country.From October 1, 1999, to December 31, 2005, we prospectively studied all patients admitted to the HSCT unit at Hospital Luis Calvo Mackenna in Santiago, Chile. Serologic studies before transplantation and weekly CMV infection surveillance (antigenemia or quantitative PCR) were routinely obtained. Patients with positive antigenemia or quantitative PCR received pre-emptive therapy with ganciclovir, and cases of unfavorable clinical evolution, persistent positive antigenemia, or quantitative PCR after 14 days of ganciclovir were treated with foscarnet.Ninety-seven patients received HSCT. Their median age was 8 years (range, 3 months to 24 years) and their overall survival was 67%. CMV reactivation was diagnosed in 26 patients. Of these, three developed CMV disease (two interstitial pneumonia, one hemorrhagic cystitis). One of the patients with pneumonia died. Risk factors identified were pre-transplant serologic status (positive recipient), acute and chronic graft versus host disease (GvHD), GvHD prophylaxis, and treatment with antithymocyte globulin.The rate and prognosis of CMV infection among children treated at our HSCT unit is similar to those reported from industrialized countries. These findings reflect adequate prevention and management of CMV infection within our program.

The main causes of complications of allogenic hematopoietic stem cell transplantation are infections and graft versus host disease.To assess the predictive value of C reactive protein (CRP) and procalcitonin (PCT) in the diagnosis of invasive bacterial infections in children with febrile neutropenia after an allogenic hematopoietic stem cell transplantation.Prospective follow up of patients aged 18 years or less, with febrile neutropenia after an allogenic hematopoietic stem cell transplantation. In all patients, cultures from sterile sites, CRP and PCT determinations were done. CRP levels were also measured prior to transplantation and three times per week for 30 days after the procedure. An independent evaluator, blinded to the results of CRP and PCT, classified children as with or without invasive bacterial infection.Thirty three patients aged 9+/-5 years (21 males) were studied. Eight had an invasive bacterial infection. Sensitivity, specificity, positive and negative predictive values of a CRPor = 90 mg/L for the diagnosis of invasive bacterial infection were 25, 80, 29 and 77%, respectively. The figures for a PCTor = 0.7 ng/ml were 43, 78, 38 and 82%, respectively. No differences in repeated CRP values measured during evolution, were observed.A CRPor = 90 mg/L or a PCTor = 0.7 ng/ml had a high specificity and negative predictive value but low sensitivity for the diagnosis of invasive bacterial infections in recipients of allogenic hematopoietic stem cell transplantation.

Background In Chile, survival estimates for pediatric patients with cancer are comparable to those in the United States and Western Europe. Approximately 80% of these patients are treated at government-supported centers, and an estimated 65% are cured. We reasoned that cure rates could be further improved if transplantation with hematopoietic stem cells were available for patients with chemotherapy-resistant malignancy. Patients and Methods Physicians and nurses were selected to be trained in international centers, and a transplantation unit was developed at Luis Calvo Mackenna Hospital in Santiago. Between October 1999 and December 2003, 59 patients received transplants. Of these, 42 were from HLA-matched family members and 11 were autologous. Results The 3-year event-free survival estimate was 72 ± 10% overall, and it was 81 ± 10% for the subgroup treated with matched related transplants. Peritransplant mortality was 6.6%. The average cost for an allogeneic transplant in our unit was US $50,000. Conclusions We are encouraged by this experience as well as by the overall survival rates and hope to expand the program. Our goal is to extend treatment to all children in the country for whom HSCT is indicated, including those who do not have HLA-identical family donors. Pediatr Blood Cancer © 2005 Wiley-Liss, Inc.