Healthcare migration in Italian paediatric haematology-oncology centres belonging to AIEOP.

BACKGROUND: In Italy, there is a network of centres headed by the Italian Association of Pediatric Hematology and Oncology (AIEOP) for the diagnosis and treatment of paediatric cancers on almost the entire national territory. Nevertheless, migration of patients in a hospital located in a region different from that of residence is a widespread habit, sometimes motivated by several reasons. The aim of this paper is to assess the impact of migration of children with cancer to AIEOP centres in order to verify their optimal distribution throughout the national territory. METHODS: To this purpose, we used information on 41,205 registered cancer cases in the database of Mod.1.01 Registry from AIEOP centres, with age of less than 20 years old at diagnosis, diagnosed from 1988 to 2017. Patients' characteristics were analysed and compared using the X2 or Fisher's exact test or Mann-Whitney test, when appropriate. Survival distributions were estimated using the method of Kaplan and Meier, and the log-rank test was used to examine differences among subgroups. RESULTS: Extra-regional migration involved overall 19.5% of cases, ranging from 23.3% (1988-1997) to 16.4% (2008-2017) (p < 0.001). In leukaemias and lymphomas we observed a mean migration of 8.8% overall, lower in the North (1.2%) and Centre (7.8%) compared to the South & Isles (32.3%). In the case of solid tumours, overall migration was 25.7%, with 4.2% in the North, 17.2% in the Centre and 59.6% in the South & Isles. For regions with overall levels of migration higher than the national average, most migration cases opted for AIEOP centres of close or even neighbouring regions. Overall survival at 10 years from diagnosis results 69.9% in migrants vs 78.3% in no migrants (p < 0.001). CONCLUSIONS: There is still a certain amount of domestic migration, the causes of which can be easily identified: migration motivated by a search for high specialization, migration due to lack of local facilities, or regions in which no AIEOP centres are present, which makes migration obligatory. Better coordination between AIEOP centres could help to reduce so-called avoidable migration, but technical and political choices will have to be considered, with the active participation of sector technicians.

Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation for Children with High-Risk Neuroblastoma Using a Reduced-Intensity Conditioning Regimen: Results from the AIEOP Trial.

Despite aggressive multimodal treatment, the outcomes of pediatric patients with high-risk (HR) neuroblastoma (NB) remain poor. The rationale for allogeneic hematopoietic stem cell transplantation (allo-HCT) to treat NB was based on the possible graft-versus-tumor effect; however, toxicity limits its efficacy. We sought to prospectively assess the feasibility and efficacy of allo-HCT using a reduced-intensity conditioning regimen in pediatric patients with HR NB in a multicenter phase II trial. Primary endpoints were the rate of neutrophil and platelet engraftment, 5-year transplantation-related mortality (TRM), and disease-free survival (DFS). Secondary endpoint measures included the incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD. Fifty-one patients were enrolled in the study. The 5-year cumulative incidence (CuI) of TRM was 29.4 ± 6.4%, and that of DFS was 11.8 ± 4.5%. Patients undergoing allo-HCT within 1 year of diagnosis or with bone marrow as their stem cell source had a higher DFS probability. The CuI of neutrophil engraftment, platelet engraftment, and grade II-IV aGVHD was 97.9 ± 2.1%, 93.8 ± 3.5%, and 47.1 ± 7.0%, respectively. The development of new therapeutic strategies could further improve disease control.

Development and Initial Validation of the ONCOREUM Score to Differentiate Childhood Cancer with Arthropathy from Juvenile Idiopathic Arthritis.

OBJECTIVE: To develop and validate a weighted score, the ONCOREUM score, that aids physicians in differentiation of cancer with arthropathy from juvenile idiopathic arthritis (JIA). STUDY DESIGN: Data were extracted from the ONCOREUM Study, a multicenter, cross-sectional investigation aimed at comparing children with cancer and arthropathy to children with JIA. Three statistical approaches were applied to develop the ONCOREUM score and assess the role of each variable in the diagnosis of cancer with arthropathy, including 2 approaches based on multivariable stepwise selection (models 1 and 2) and 1 approach on a Bayesian model averaging method (model 3). The ß coefficients estimated in the models were used to assign score points. Considering that not missing a child with cancer is a mandatory clinical objective, discriminating performance was assessed by fixing sensitivity at 100%. Score performance was evaluated in both developmental and validation samples (representing 80% and 20% of the study population, respectively). RESULTS: Patients with cancer and arthropathy (49 with solid tumors and 46 with hematologic malignancies without peripheral blasts) and 677 patients with JIA were included. The highest area under the receiver operating characteristic (ROC) curve (AUC) in the validation data set was yielded by model 1, which was selected to constitute the ONCOREUM score. The score ranged from -18 to 21.8, and the optimal cutoff obtained through ROC analysis was -6. The sensitivity, specificity, and AUC of the cutoff in the validation sample were 100%, 70%, and 0.85, respectively. CONCLUSIONS: The ONCOREUM score is a powerful and easily applicable tool that may facilitate early differentiation of malignancies with articular complaints from JIA.

[Incidence of cancer among children and adolescents (0-19 years) in Lazio Region (Central Italy), 2009-2015]. / Incidenza di tumori nella popolazione infantile e adolescenziale (0-19 anni) della Regione Lazio, anni 2009-2015.

OBJECTIVES: to investigate, for the first time, the incidence of cancer (years 2009-2015) and geographical distribution among children and adolescents with cancer diagnosis in Lazio Region (Central Italy). DESIGN: to compute incidence rates of childhood cancers from Lazio Region Childhood Cancer Registry (LRCCR) database, established in 2015, and to compare results with national figures for 2012 provided by the Italian cancer registries network (AIRTUM). SETTING AND PARTICIPANTS: all new cases of malignant tumours (behaviour: /3 of ICD-O-3 classification) and all central nervous system tumours were selected, regardless of behaviour (/0, /1, /3) in children and adolescents (0-19 years) registered in the LRCCR data base. MAIN OUTCOME MEASURES: it was computed: • the raw and the direct standardised rates for the 0-14-year and the 15-19-year age groups for total malignant tumours of the ICCC-3 classification by area (province level and municipality of Rome); • Relative Risks (RR) for area-specific rate compared with that of the Lazio Region and 95% Confidence Intervals (95%CI). RESULTS: a total of 1,782 incident cases were recorded in 2009-2015; of these, 91.4% were confirmed by a pathology report. Standardized Incidence Rate for all malignant tumours is 207.2×1,000,000 (95%CI 195.5-219.5) in children and 335.1×1,000,000 (95%CI 308.9-361.2) in adolescents. Compared to the Lazio Region, a higher incidence of tumours is observed in Rome municipality (RR 1.09; 95%CI 0.98-1.20) and in the Frosinone province (RR 1.07; 95%CI 0.91-1.25) for the whole 0-19-year age group. CONCLUSIONS: compared to the pooled AIRTUM figures for 2003-2008, Lazio Region showed a higher incidence for all cancers, both in children and adolescents, and for specific tumours, such as leukaemia in children and thyroid carcinoma in adolescents. Apart from the diverse observation period, these differences may be due to a higher registry sensitivity of the childhood specialized registry compared to general population registries. The observed incidence excesses for specific geographical areas and tumours deserve further investigations. Overall, in its first seven years of activity, the Lazio childhood cancer registry was able to provide reliable epidemiological figures of cancer incidence in children and adolescents in the Italian context.

Immune cytopenias as a continuum in inborn errors of immunity: An in-depth clinical and immunological exploration.

BACKGROUND: Immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN) are disorders characterized by immune-mediated destruction of hematopoietic cell lineages. A link between pediatric immune cytopenias and inborn errors of immunity (IEI) was established in particular in the combined and chronic forms. OBJECTIVE: Aim of this study is to provide clinical-immunological parameters to hematologists useful for a prompt identification of children with immune cytopenias deserving a deeper immunological and genetic evaluation. METHODS: We retrospectively collected 47 pediatric patients with at least one hematological disorder among which persistent/chronic ITP, AIHA, and AIN, aged 0-18 years at onset of immune cytopenias and/or immune-dysregulation. The cohort was divided into two groups (IEI+ and IEI-), based on the presence/absence of underlying IEI diagnosis. IEI+ group, formed by 19/47 individuals, included: common variable immune deficiency (CVID; 9/19), autoimmune lymphoproliferative syndrome (ALPS; 4/19), DiGeorge syndrome (1/19), and unclassified IEI (5/19). RESULTS: IEI prevalence among patients with ITP, AIHA, AIN, and Evans Syndrome was respectively of 42%, 64%, 36%, and 62%. In IEI+ group the extended immunophenotyping identified the presence of statistically significant (p < .05) specific characteristics, namely T/B lymphopenia, decrease in naїve T-cells%, switched memory B-cells%, plasmablasts%, and/or immunoglobulins, increase in effector/central memory T-cells% and CD21low B-cells%. Except for DiGeorge and three ALPS patients, only 2/9 CVID patients had a molecular diagnosis for IEI: one carrying the pathogenic variant CR2:c.826delT, the likely pathogenic variant PRF1:c.272C> and the compound heterozygous TNFRSF13B variants p.Ser144Ter (pathogenic) and p.Cys193Arg (variant of uncertain significance), the other one carrying the likely pathogenic monoallelic variant TNFRSF13B:p.Ile87Asn. CONCLUSION: The synergy between hematologists and immunologists can improve and fasten diagnosis and management of patients with immune cytopenias through a wide focused clinical/immunophenotypical characterization, which identifies children worthy of IEI-related molecular analysis, favouring a genetic IEI diagnosis and potentially unveiling new targeted-gene variants responsible for IEI phenotype.

Concordance between paediatric self-reports and parent proxy reports on fatigue: A multicentre prospective longitudinal study.

PURPOSE: To investigate the degree of concordance on fatigue assessment between children and adolescents with cancer and their parents, and its changes over time. METHOD: Multicentre longitudinal study. RESULTS: Data from 134 dyads were analysed. The mean age of patients was 11.7 years; caregivers had a mean age of 44.1 years. Almost 90% of patients already reported mild or moderate fatigue at the time of diagnosis, decreasing to 69.7% after one year. Concordance on the total fatigue improved over time for the total sample, moving from moderate at the time of diagnosis to good concordance after one year. CONCLUSIONS: This was the first study with a longitudinal design investigating concordance between paediatric self-reports and parent proxy reports on fatigue. It showed how concordance between proxies and patients changed over time reaching a good level after one year from the cancer diagnosis.

The Italian Registry for Primary Immunodeficiencies (Italian Primary Immunodeficiency Network; IPINet): Twenty Years of Experience (1999-2019).

Primary immunodeficiencies (PIDs) are heterogeneous disorders, characterized by variable clinical and immunological features. National PID registries offer useful insights on the epidemiology, diagnosis, and natural history of these disorders. In 1999, the Italian network for primary immunodeficiencies (IPINet) was established. We report on data collected from the IPINet registry after 20 years of activity. A total of 3352 pediatric and adult patients affected with PIDs are registered in the database. In Italy, a regional distribution trend of PID diagnosis was observed. Based on the updated IUIS classification of 2019, PID distribution in Italy showed that predominantly antibody deficiencies account for the majority of cases (63%), followed by combined immunodeficiencies with associated or syndromic features (22.5%). The overall age at diagnosis was younger for male patients. The minimal prevalence of PIDs in Italy resulted in 5.1 per 100.000 habitants. Mortality was similar to other European registries (4.2%). Immunoglobulin replacement treatment was prescribed to less than one third of the patient cohort. Collectively, this is the first comprehensive description of the PID epidemiology in Italy.

Comparison of Hodgkin's Lymphoma in Children and Adolescents. A Twenty Year Experience with MH'96 and LH2004 AIEOP (Italian Association of Pediatric Hematology and Oncology) Protocols.

Adolescents and young adults (AYAs) represent a distinct group of patients. The objectives of this study were: To compare adolescent prognosis to that of younger children; to compare the results achieved with the two consecutive protocols in both age groups; to analyze clinical characteristics of children and adolescents. Between 1996 and 2017, 1759 patients aged <18 years were evaluable for the study. Five hundred and sixty patients were treated with the MH'96 protocol and 1199 with the LH2004 protocol. Four hundred and eighty-two were adolescents aged ≥15 years. Patients in both age groups showed very favorable prognoses. In particular, OS improved with the LH2004 protocol, especially in the adolescent group and in the low risk group, where radiation therapy was spared. Adolescent characteristics differed significantly from the children's according to sex, histology, and the presence of symptoms. Remarkable is the decrease both in mixed cellularity in the children and in low stages in both age groups in the LH2004 protocol with respect to MH'96 protocol. Based on our experience, adopting pediatric protocols for AYA does not compromise patient outcomes.

Enteral nutrition protects children undergoing allogeneic hematopoietic stem cell transplantation from blood stream infections.

Enteral Nutrition (EN) is recommended as first line nutritional support for patients undergoing Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT), but only few studies exist in the literature which compare EN to Parenteral Nutrition (PN) in the paediatric population.Forty-two consecutive paediatric patients undergoing allo-HSCT at our referral centre between January 2016 and July 2019 were evaluated. Post-transplant and nutritional outcomes of patients receiving EN for more than 7 days (EN group, n = 14) were compared with those of patients receiving EN for fewer than 7 days or receiving only PN (PN group, n = 28). In the EN group, a reduced incidence of Blood Stream Infections (BSI) was observed (p = 0.02) (n = 2 vs. n = 15; 14.3% vs. 53.6%). The type of nutritional support was also the only variable independently associated with BSI in the multivariate analysis (p = 0.03). Platelet engraftment was shorter in the PN group than in the EN group for a threshold of > 20*109/L (p = 0.04) (23.1 vs 35.7 days), but this correlation was not confirmed with a threshold of > 50*109/L. The Body Mass Index (BMI) and the BMI Z-score were no different in the two groups from admission to discharge.Our results highlight that EN is a feasible and nutritionally adequate method of nutritional support for children undergoing allo-HSCT in line with the present literature. Future functional studies are needed to better address the hypothesis that greater intestinal eubyosis maintained with EN may explain the observed reduction in BSI.

Carnitine longitudinal pattern in preterm infants <1800 g body weight: a case-control study.

BACKGROUND: The aim of this study is to investigate free carnitine (C0) and total acylcarnitine levels (AC) in preterm infants with BW < 1800 g and the relationship with neonatal and perinatal factors. METHODS: Ninety-three thousand two hundred and ninety-three newborns were screened between 2011 and 2013. Dried blood samples (DBS) were collected at 48-72 h, 14, and 30 days of age. We studied 92 consecutive preterm (BW < 1800 g) infants with low carnitine levels at 30 days of life (Group 1). As controls, we included the first 92 cases (BW < 1800 g) with normal carnitine levels (Group 2) and another 92 at or near-term newborns with BW > 1800 g (Group 3). RESULTS: Compared to 48-72 h levels, C0 and AC decreased at 14 and 30 days of life in Groups 1 and 2 (p < 0.001). In Group 2, the percentage of children with carnitine-free parenteral nutrition (PN) and BW < 1000 g was lower than in Group 1 (p < 0.001). Only in Group 2 did C0 increase at 30 days (p < 0.001). The multivariate regression analysis confirmed the influence of body weight and type of nutrition on C0 and AC. CONCLUSION: Body weight and type of nutrition influenced the carnitine longitudinal pattern.

Late mortality and causes of death among 5-year survivors of childhood cancer diagnosed in the period 1960-1999 and registered in the Italian Off-Therapy Registry.

INTRODUCTION: Advances in paediatric oncology led to the increase in long-term survival, revealing the burden of therapy-related long-term side effects. We evaluated overall and cause-specific mortality in a large cohort of Italian childhood cancer survivors (CCSs) and adolescent cancer survivors identified through the off-therapy registry. MATERIALS AND METHODS: CCSs alive 5 years after cancer diagnosis occurring between 1960 and 1999 were eligible; the last follow-up was between 2011 and 2014. Outcomes were reported as standardised mortality ratios (SMRs) and absolute excess risks (AERs). RESULTS: Among 12,214 CCSs, 1113 (9.1%) deaths occurred. Survival at 35 years since diagnosis was 87% (95% confidence interval [CI]: 86-88) and at 45 years was 81% (95% CI: 77-84). CCSs had an 11-fold increased risk of death (SMR 95% CI: 10.7-12), corresponding to an AER of 48 (95% CI: 45-51). Mortality decreased by 60% for survivors treated most recently (1990-1999). The most frequent causes of death were recurrence of the original cancer (56%), a subsequent neoplasm (19%) and cardiovascular diseases (5.8%). Among those who survived at least 15 years after diagnosis, a secondary malignancy was the leading cause of death. CONCLUSIONS: This study confirms the impact of recent advances in anticancer therapy in reducing mortality, mainly attributable to recurrence but also to other causes. However, overall mortality continues to be higher than in the general population. A long-term follow-up is needed to prevent late mortality due to secondary neoplasms and non-neoplastic causes in CCSs.

Long-term results of the AIEOP MH'96 childhood Hodgkin's lymphoma trial and focus on significance of response to chemotherapy and its implication in low risk patients to avoid radiotherapy.

Identify a subset of early-stage HL children (GR1) curable with limited chemotherapy+/-radiotherapy; improve outcome of intermediate (GR2) and high-risk (GR3) patients; establish impact of response to chemotherapy evaluated with conventional imaging (CI). One hundred and sixty GR1-patients received 3ABVD + involved-field (IF) low-dose (LD) (20 Gy) irradiation if mediastinal mass or partial response (PR) after chemotherapy. Eighty-five GR2- and 315 GR3-patients received 4 and 6 COPP/ABV + IFRT, respectively. The 63 GR1 patients spared from radiotherapy had 15-year survival and EFS of 100 and 84.5%, respectively. The GR2 and GR3 15-year FFP were 84.7 and 78.6%, respectively. No different prognosis for patients in CR or PR evaluated during and after chemotherapy was observed. In conclusion, low-risk patients in CR may be successfully treated with radiation-free, low-intensity chemotherapy. Good, but less satisfactory, results were registered in GR2 and GR3. Response evaluated with CI is not a prognostic factor, but permits identification of low-risk patients who can avoid radiotherapy.

Tissue Doppler Imaging for anthracycline cardiotoxicity monitoring in pediatric patients with cancer.

BACKGROUND: Cardiotoxic effects of anthracycline therapy are a major cause of morbidity for childhood cancer survivors. The aim of this retrospective evaluation is to assess the efficacy of Tissue Doppler Imaging in the early detection of myocardial alterations in these patients. METHODS: A population of 50 childhood cancer survivors (32 males and 18 females) who have been treated with anthracyclines was evaluated by standard and TDI echocardiographic examination of the basal and median region of the interventricular septum (IVSb, IVSm), of the left ventricular posterior wall (LVPWb, LVPWm), and of the mitral annulus; the results were compared with those obtained from a population of 50 healthy age-matched and sex-matched controls by using the Student test. The clinical and echocardiographic data of the two groups were compared also with the independent samples t-test. All data were expressed as mean ± standard deviation. A two-tailed P-value < 0.05 was considered statistically significant. Statistical analysis was performed using STATA 7.0. RESULTS: The case-control analysis showed statistically significant differences (p < 0,05) between the patients and the controls values. The systolic performance of the patients was normal (LVEF (p = 0,0029) and LVFS (p = 0,0002)). Statistically significant differences between patients and controls were found for diastolic function measurements obtained with PW Doppler such as IVRT (p = 0,0000), DT (p = 0,0041), E (p = 0,0000), A (p = 0,0458), even if E/A ratio was not altered. TDI analysis also show significant differences between patients and controls in both LVPW and IVS (basal and middle segments); E/E' ratio and E'/A' ratio did not vary significantly. Linear Regression and multivariate analysis showed that Hematopoietic Stem Cell Transplantation had the highest impact on our measurements. CONCLUSIONS: The results showed a myocardial diastolic impairment with preserved ejection fraction. Since the median follow-up time of our cohort was 2 years, further evaluation is needed to better define the diastolic alterations. TDI analysis showed high sensitivity for the detection of mild myocardial dysfunction; the implementation of this novel method as standard practice in the follow-up of selected childhood cancer survivors might help to achieve a better management of long-term complications of cardiotoxic chemotherapy.

Outcome of children with acute leukemia given HLA-haploidentical HSCT after αß T-cell and B-cell depletion.

Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children with acute leukemia (AL) either relapsed or at high-risk of treatment failure. We developed a novel method of graft manipulation based on negative depletion of αß T and B cells and conducted a prospective trial evaluating the outcome of children with AL transplanted with this approach. Eighty AL children, transplanted between September 2011 and September 2014, were enrolled in the trial. All children were given a fully myeloablative preparative regimen. Anti-T-lymphocyte globulin from day -5 to -3 was used for preventing graft rejection and graft-versus-host disease (GVHD); no patient received any posttransplantation GVHD prophylaxis. Two children experienced primary graft failure. The cumulative incidence of skin-only, grade 1-2 acute GVHD was 30%; no patient developed extensive chronic GVHD. Four patients died, the cumulative incidence of nonrelapse mortality being 5%, whereas 19 relapsed, resulting in a 24% cumulative incidence of relapse. With a median follow-up of 46 months for surviving patients, the 5-year probability of chronic GVHD-free, relapse-free survival (GRFS) is 71%. Total body irradiation-containing preparative regimen was the only variable favorably influencing relapse incidence and GRFS. The outcomes of these 80 patients are comparable to those of 41 and 51 children given transplantation from an HLA-identical sibling or a 10/10 allelic-matched unrelated donor in the same period. These data indicate that haplo-HSCT after αß T- and B-cell depletion represents a competitive alternative for children with AL in need of urgent allograft. This trial was registered at www.clinicaltrials.gov as #NCT01810120.

Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol.

In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow-cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica-AML 2002/01 trial. At the end of the first induction course, MRD was <0·1% in 69, 0·1-1% in 16 and >1% in 51 patients. The 8-year disease-free survival (DFS) of 125 children in morphological complete remission and with MRD <0·1%, 0·1-1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow-cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post-remission treatment.

[The contribution of the Italian Association of paediatric haematology and oncology (AIEOP)]. / Il contributo dell'Associazione italiana di ematologia e oncologia pediatrica (AIEOP).

Since 1972, children affected by cancer took advantage from multi-centric diagnostic and therapeutic protocols produced by the Italian Association of paediatric haematology and oncology (AIEOP). At the beginning, these protocols were used in few well-trained centres, later in almost all Italian haemato-oncological centres. The need of a careful monitoring of his own activity induced AIEOP to achieve, in 1989, an Italian hospital- based registry (database Mod.1.01) of malignant tumours diagnosed and treated in the participating centres, with the aim to quantify the number of cases diagnosed and treated in the different centres, the agreement (or not) to official diagnostic- therapeutic protocols, and the extraregional migration. The database Mod.1.01, which is available via web to the current 55 AIEOP centres since 2000, recruits annually about 1,400 children (0-14 years) and 200 adolescents (15-19 years). While the first accounts for over 90% of expected subjects, the latter are only 25%. Leukaemias (30% of cases) are the most frequent childhood cancers, followed by central nervous system (CNS) tumours and lymphomas, 18% of cases both. In children, leukaemias (34%) are prevalent, mostly acute lymphoblastic leukaemia (26%), followed by CNS tumours (18%); in adolescents, lymphomas (30%) are prevalent, mostly Hodgkin lymphomas (22%), followed by bone sarcomas (16%). The recruitment of registered cases in AIEOP protocols is overall good both for children (70%) and for adolescents (60%), achieving outstanding results in leukaemia protocols. Extraregional migration of patients for diagnosis and therapy is decreasing over time, being currently about 20%, higher in adolescents, in solid tumours, and in residents in South Italy and in the islands. On the contrary, an increase of subjects born and resident abroad who are hospitalised in AIEOP centres for diagnosis and treatment, accounting at present for 5% of all cases, was observed. The results confirm that the database Mod.1.01 can be a valid tool able to contribute to epidemiologic research on childhood cancer in Italy.

Time trends of cancer incidence in childhood in Campania region: 25 years of observation.

BACKGROUND: Childhood cancer is relatively uncommon and the European age-standardized rate was 164 new case per million per year among children 0 to 14 years of age (95 % CI 158-170). Aims of our study are to evaluate the cases of these malignant diseases observed between 0 and 15 years of age in the Campania region between 1990 and 2014, the ration between observed and expected cases by disease and province of residence. Also we studied the percentage of extra-regional migration over the time by disease and province of residence. METHODS: In this study we reported the patients with malignant disease observed in 25 years (1990-2014) based on the specialized registry, the Mod. 1.01 of the AIEOP (Association Italian Pediatric Hematology-Oncology). The size of the monitored population also allowed us to systematically examine five time trends: 1990-94: 1995-99; 2000-04; 2005-09; and 2010-14. RESULTS: Between 1990 and 2014 a total of 3655 malignant neoplasms were reported: Napoli province (2059 cases), Salerno province (625), Caserta province (589), Avellino province (229), and Benevento province (153). Epidemiological data suggested that about 4100 cases could be expected in Campania region during the same period. The overall ratio between observed (O) and expected (E) numbers of cases in the five periods considered rose gradually from 0.69 in the first period to 0.76, then 0.82, 0.91, and 0.94, in the other periods considered. The extra-regional migration involved 1029 cases (28.1 %), showing a reduction from 33.7 % of the first period to 20.3 % of the last period considered. Considering single province of residence we observed the lowest rate of migration in Napoli and Caserta province, whereas higher levels were observed in the other provinces. For all provinces, except Salerno, the extra-regional migration declined significantly over time. CONCLUSIONS: The present findings showed an increase over time of O/E ratio, probably due to improvement in the organization of centers and greater trust of families in local centers. It is possible to further improve the efficiency of healthcare system of Campania region and migration can be reduced with a more rational use of hospitals throughout region.

Adolescents with Cancer in Italy: Improving Access to National Cooperative Pediatric Oncology Group (AIEOP) Centers.

This analysis compared the numbers of patients treated at Italian pediatric oncology group (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]) centers with the numbers of cases predicted according to the population-based registry. It considered 32,431 patients registered in the AIEOP database (1989-2012). The ratio of observed (O) to expected (E) cases was 0.79 for children (0-14 years old) and 0.15 for adolescents (15-19 years old). The proportion of adolescents increased significantly over the years, however, from 0.05 in the earliest period to 0.10, 0.18, and then 0.28 in the latest period of observation, suggesting a greater efficacy of local/national programs dedicated to adolescents.

Road Traffic Pollution and Childhood Leukemia: A Nationwide Case-control Study in Italy.

BACKGROUND: The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. AIM OF THE STUDY: We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. METHODS: We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic-ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. RESULTS: We observed an increase in risk for AnLL, and at a lower extent for ALL, with indicators of exposure to traffic pollutants. In particular, the risk was associated to the report of closeness of the house to traffic lights and to the passage of trucks (OR: 1.76; 95% CI 1.03-3.01 for ALL and 6.35; 95% CI 2.59-15.6 for AnLL). The association was shown also in the analyses limited to AML and in the stratified analyses and in respect to the house in different period of life. CONCLUSIONS: Results from the SETIL study provide some support to the association of traffic related exposure and risk for AnLL, but at a lesser extent for ALL. Our conclusion highlights the need for leukemia type specific analyses in future studies. Results support the need of controlling exposure from traffic pollution, even if knowledge is not complete.