Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the ...changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time.
Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome.
Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, IQR 4.9-15.1), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674).
In this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates.
Etiological diagnosis of fever in children with sickle cell disease (SCD) is often challenging. The aim of this study was to analyze the pattern of inflammatory biomarkers in SCD febrile children and ...controls, in order to determine predictors of severe bacterial infection (SBI).
A prospective, case-control study was carried out during 3 years, including patients younger than 18 years with SCD and fever (cases) and asymptomatic steady-state SCD children (controls). Clinical characteristics and laboratory parameters, including 10 serum proinflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17a, IFN-γ and TNF-α) and comparisons among study subgroups were analyzed.
A total of 137 patients (79 cases and 58 controls) were included in the study; 78.5% males, median age 4.1 (1.7-7.5) years. Four cases were diagnosed with SBI, 41 viral infection (VI), 33 no proven infection (NPI) and 1 bacterial-viral coinfection (the latter excluded from the subanalyses). IL-6 was significantly higher in patients with SBI than in patients with VI or NPI (163 vs 0.7 vs 0.7 pg/ml, p < 0.001), and undetectable in all controls. The rest of the cytokines analyzed did not show any significant difference. The optimal cut-off value of IL-6 for the diagnosis of SBI was 125 pg/mL, with high PPV and NPV (PPV of 100% for a prevalence rate of 5, 10 and 15% and NPV of 98.7%, 97.3% and 95.8% for those prevalences rates, respectively).
We found that IL-6 (with a cut-off value of 125 pg/ml) was an optimal marker for SBI in this cohort of febrile SCD children, with high PPV and NPV. Therefore, given its rapid elevation, IL-6 may be useful to early discriminate SCD children at risk of SBI, in order to guide their management.
Sickle cell disease (SCD) describes a set of chronic inherited anemias characterized by hemolysis, episodes of vaso-occlusion, and high infectious risk, with high morbidity and mortality. Newborn ...screening (NBS) for SCD allows family health education and early start of infectious prophylaxis. In the Community of Madrid, a pilot universal NBS study found that the SCA birth prevalence was 1/5851 in newborns, higher than expected, confirming the need to include early detection in the NBS program. The aim of the present prospective single-center study is to analyze the results of newborn SCD screening in Madrid in terms of epidemiological data and its inclusion in a comprehensive care program during the last 15 years, between 1st of May 2003 and 1st of May 2018. During the study period, 1,048,222 dried bloodspots were analyzed. One hundred ninety-seven patients were diagnosed with possible SCD (HPLC phenotype of FS, FSA, FSC, FSE, FSD
Punjab
, FSO
Arab
), with 187 patients finally confirmed (birth prevalence 1/5552 newborns, 0.18 per 1000 live births), and 1 out of 213 infants carried Hb S. All of them were seen by a specialist clinician; median age at the first visit consultation was 35 days and median age at the beginning of penicillin treatment was 66 days. The Madrid SCD NBS program achieved high rates of sensitivity and specificity and good quality of care assistance. Establishing a good relationship with the family, a strong education program, and a multidisciplinary team that includes social workers and a psychologist are needed to ensure the success of early intervention.
A total of 192 pediatric patients, median age 8.6 years, with high‐risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo‐HSCT) using post‐transplantation ...cyclophosphamide (PT‐Cy), or ex vivo T cell‐depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT‐Cy for graft‐vs‐host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3‐depleted peripheral blood stem cells (PBSCs) by either CD34+ selection, CD3+CD19+ depletion, TCRαβ+CD19+ depletion or CD45RA+ depletion, added to CD34+ selection for GvHD prophylaxis. The PBSCs were the only source in patients following ex vivo TCD haplo‐HSCT; bone marrow was the source in 9 of 41 patients following PT‐CY haplo‐HSCT. Engraftment was achieved in 91.3% of cases. A donor younger than 30 years, and the development of chronic GvHD were positive factors influencing survival, whereas positive minimal residual disease (MRD) before transplant and lymphoid disease were negative factors. The probability of relapse increased with lymphoid malignancies, a donor killer‐cell immunoglobulin‐like receptor (KIR) haplotype A and positive MRD pretransplant. No difference was found in overall survival, disease‐free survival or relapse incidence between the two platforms. Relapse is still of concern in both platforms, and it should be the focus of future efforts. In conclusion, both platforms for haplo‐HSCT were effective and could be utilized depending on the comfort level of the center.
Fanconi anemia (FA) is characterized by chromosome fragility, bone marrow failure (BMF) and predisposition to cancer. As reverse genetic mosaicism has been described as “natural gene therapy” in ...patients with FA, we sought to evaluate the clinical course of a cohort of FA mosaic patients followed at referral centers in Spain over a 30‐year period. This cohort includes patients with a majority of T cells without chromosomal aberrations in the DEB‐chromosomal breakage test. Relative to non‐mosaic FA patients, we observed a higher proportion of adult patients in the cohort of mosaics, with a later age of hematologic onset and a milder evolution of (BMF). Consequently, the requirement for hematopoietic stem cell transplant (HSCT) was also lower. Additional studies allowed us to identify a sub‐cohort of mosaic FA patients in whom the reversion was present in bone marrow (BM) progenitor cells leading to multilineage mosaicism. These multilineage mosaic patients are older, have a lower percentage of aberrant cells, have more stable hematology and none of them developed leukemia or myelodysplastic syndrome when compared to non‐mosaics. In conclusion, our data indicate that reverse mosaicism is a good prognostic factor in FA and is associated with more favorable long‐term clinical outcomes.
Background
Although highly prevalent throughout the world, the accurate prevalence of hemoglobinopathies in Spain is unknown.
Procedure
This study presents data on the national registry of ...hemoglobinopathies of patients with thalassemia major (TM), thalassemia intermedia (TI), and sickle cell disease (SCD) in Spain created in 2014. Fifty centers reported cases retrospectively. Data were registered from neonatal screening or from the first contact at diagnosis until last follow‐up or death.
Results
Data of the 715 eligible patients were collected: 615 SCD (497 SS, 64 SC, 54 SBeta phenotypes), 73 thalassemia, 9 CC phenotype, and 18 other variants. Most of the SCD patients were born in Spain (65%), and 51% of these were diagnosed at newborn screening. Median age at the first diagnosis was 0.4 years for thalassemia and 1.0 years for SCD. The estimated incidence was 0.002 thalassemia cases and 0.03 SCD cases/1,000 live births. Median age was 8.9 years (0.2–33.7) for thalassemia and 8.1 years (0.2–32.8) for SCD patients. Stroke was registered in 16 SCD cases. Transplantation was performed in 43 TM and 23 SCD patients at a median age of 5.2 and 7.8 years, respectively. Twenty‐one patients died (3 TM, 17 SCD, 1 CC) and 200 were lost to follow‐up. Causes of death were related to transplantation in three patients with TM and three patients with SCD. Death did not seem to be associated with SCD in six patients, but nine patients died secondary to disease complications. Overall survival was 95% at 15 years of age.
Conclusions
The registry provides data about the prevalence of hemoglobinopathies in Spain and will permit future cohort studies and the possibility of comparison with other registries
Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute ...respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN.
Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV.
There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08).
A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiologic methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.
Patients with thalassaemia major (TM) and sickle cell disease (SCD) in Spain have been counted since the creation of the Spanish registry of haemoglobinopathies (REHem). The objective of this paper ...is to update the published data after the increase in cases due to the inclusion of adults and introduction of new-born screening in almost the whole country.
An observational, descriptive, multicentre and ambispective study that included patients with haemoglobinopathies registered in the REHem, started in January 2014 and followed up annually. The data presented correspond until December 31, 2017.
Nine hundred and fifty-nine patients were collected. There were 75 cases of thalassaemia (62 TM), 826 of ECF and 58 of other types of haemoglobinopathies. The main diagnostic reason in the TM cohort was anaemia symptoms (70.6%), with a mean age at diagnosis of .7 years; in the SCD cohort it was neonatal screening (33.1%), with a mean age at diagnosis of 2.7 years; 26 patients with TM (41.9%) and 30 with SCD (3.6%) underwent a transplant. There were 2 deaths (3.2%) with TM and 19 (2.3%) with SCD. Overall survival was 96.7% in the TM and 97.5% in the SCD cases at 15 years.
Since the previous publication and after the diffusion of new-born screening, the most frequent diagnostic method, to the majority of autonomous regions, and the inclusion of adult patients to the registry, the REHem has increased by more than 240 cases, reaching a total of 959 records.
In May 2003, Madrid established the universal newborn screening (NBS) for sickle cell disease (SCD). However, there are no studies resembling the evolution of a SCD neonate cohort followed according ...to national guidelines in Spain. The aim of this study is to describe the morbimortality and the stroke prevention programme in patients diagnosed by SCD NBS in Madrid. This is a multicentre, observational, prospective cohort study between 2003 and 2018; 187 patients diagnosed with SCD were included (151 HbSS, 6 HbSβ
0
, 27 HbSC, 3 HbSβ +), and median follow-up was 5.2 years (0.03–14.9). There were 5 deaths: 2 related to SCD in patients with severe genotype (HbSS/HbSβ
0
). Overall survival reached 95% and SCD-related survival 96.8%. The most frequent events were fever without focus, vaso-occlusive crises and acute chest syndromes. Eight strokes occurred in 5 patients which led to a 90.7% stroke-free survival in severe genotype patients (first stroke rate, 0.54 per 100 patient-years). Transcranial Doppler (TCD) was performed in 95% of eligible patients; 75% of children with pathological TCD remained stroke-free. Regarding HbSS/HbSβ
0
patients, 50.1% received hydroxyurea and 9.5% haematopoietic stem cell transplantation. This study reflects the evolution of Madrid SCD cohort and provides morbimortality data similar to other developed countries.
Introduction
The increase in the number of patients with hemoglobinopathies in Europe in recent decades highlights the need for more detailed epidemiological information in Spain. To fulfil this ...need, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) sponsored the creation of a national registry of hemoglobinopathies known as REHem-AR (Spanish Registry of Hemoglobinopathies and Rare Anemias). Data from the transfusion-dependent (TDT) and non–transfusion-dependent (NTDT) β-thalassemia cohorts are described and analyzed.
Methods
We performed an observational, multicenter, and ambispective study, which included patients of any age with TDT and NTDT, registered up to December 31, 2021.
Results
Among the 1741 patients included, 168 cases of thalassemia were identified (103 TDT and 65 NTDT-patients). Survival at 18 years was 93% for TDT and 100% for NTDT. Regarding management, 80 patients with TDT (77.7%) and 23 patients with NTDT (35.4%) started chelation treatment during follow-up, with deferasirox being the most widely used. A total of 76 patients within the TDT cohort presented at least 1 complication (73.8%), the most frequent being hemosiderosis and osteopenia-osteoporosis. Comparison of both cohorts revealed significant differences in the diagnosis of hepatic hemosiderosis (
p
= 0.00024), although these were not observed in the case of cardiac iron overload (
p
= 0.27).
Discussion
Our registry enabled us to describe the management of β thalassemia in Spain and to analyze the morbidity and mortality of the cohorts of patients with TDT and NTDT. Complications related to iron overload in TDT and NTDT account for most of the morbidity and mortality of the disease, which is associated with a considerable social, psychological, and economic impact, although cardiac, osteopathy and endocrinological complications requiring more attention. The convenience and simplicity of online registries make it possible to homogenize variables and periodically update data, thus providing valuable information on these diseases.
PDF
