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Infection is a significant cause of death in patients with aplastic anaemia (AA). However, few studies have examined the characteristics of infections in patients with AA, especially in children. The aim of this retrospective study was to evaluate the incidence and types of infections in a large cohort of paediatric patients with AA referred to eight AIEOP (Italian Association of Paediatric Oncology and Haematology) centres in Italy. The study included 78 patients, 45 boys and 33 girls, median age 9.29 yrs (1st-3rd quartile 3.59-13.09) diagnosed with AA. During the study period, 111 infectious episodes were observed in 42 (54%) patients. Fifty-one (46%) episodes were fever of unknown origin and 60 (54%) were documented infections (DI). In this group, microbiologically documented infection (MDI) with bacteremia accounted for 23 (38%) episodes, MDI without bacteremia for 7 (12%), clinically documented infection for 25 (42%) and invasive fungal diseases for 5 (8%). The rate (episodes/1000 d at risk) was similar in severe aplastic anemia and very severe aplastic anemia both before and after day 120. During the first 120 d from diagnosis, the cumulative risk of a DI was 21% (95% CI 12-29) with the last episode at day 117, but the 50% of episodes were observed in the first 24 d. After day 120, the cumulative risk of DI was again 21% (95% CI 12-29), with the last episode at day 445 of follow-up, with 50% of episodes observed in the first 120 d of observation (240 d from the diagnosis of AA). We found a statistically significant association between the grade of aplasia at diagnosis and the incidence of IEs (P = 0.0002). No association was found between gender, age at diagnosis, response at day +120 and at day +180, use of G-CSF and occurrence of IEs. The actuarial overall survival at 5 yrs was 90% ± 3.6. The mortality rate attributable to infection complication was 9%. This is a large paediatric cohort study reporting the epidemiology of infectious complications in children with AA and that allow us to compare the epidemiological data in this diseases with that of the most recent studies in neutropenic children with cancer. Our findings confirm that infections represent the main cause of death in patients with AA and they are important for the design of management strategies of febrile neutropenia in these patients.

Autoimmune lymphoproliferative disorders, including autoimmune lymphoproliferative syndrome (ALPS) and Dianzani autoimmune lymphoproliferative disease (DALD), are inherited defects of the Fas apoptotic pathway characterized by lymphoid accumulation and autoimmune manifestations. We report the molecular, clinical, immunologic features and the long-term progress of 31 patients. Four carried Fas gene mutations and one also displayed a caspase 10 polymorphism that probably contributed to the phenotype. Seven patients developed antibody deficiency and their clinical pictures overlapped those of subjects with common variable immunodeficiency (CVID). We postulate the existence of a disorder that involves the Fas pathway and displays the characteristics of both autoimmune lymphoproliferative disease and CVID.

Diamond-Blackfan anemia (DBA) is a rare, pure red blood cell aplasia of childhood caused by an intrinsic defect in erythropoietic progenitors. Malformations occur in about 40% of patients. More than half of patients respond to steroids; non-responders need chronic transfusions or stem cell transplantation (SCT). Mutations in the gene encoding ribosomal protein S19 are found in 25% of patients, but the link with erythropoiesis is unclear. A second DBA locus has been found on chromosome 8p22-p23; analysis of genes of the region is in progress.We present clinical and molecular data from 97 Italian DBA patients and a review of the literature.We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Our data, however, and a thorough review of literature show a worse outcome (expressed as transfusion dependence) in patients with mutations that completely abolish one allele, i.e. gross chromosomal rearrangements and mutations at the initiation codon. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. A recurrent missense mutation (Arg62Trp) is associated with transfusion dependence in eight of the nine reported cases.Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials.

Background:Cancer epidemiology is unique in adolescents and young adults (AYAs; aged 15-39 years). The European Society for Medical Oncology/European Society for Paediatric Oncology (ESMO/SIOPE) AYA Working Group aims to describe the burden of cancers in AYAs in Europe and across European Union (EU) countries.Patients and methods:We used data available on the Global Cancer Observatory. We retrieved crude and age-standardised (World Standard Population) incidence and mortality rates. We reported about AYA cancer burden in Europe and between 28 EU member states. We described incidence and mortality for all cancers and for the 13 cancers most relevant to the AYA population.Results:Incidence and mortality varied widely between countries with the highest mortality observed in Eastern EU countries. Cancers of the female breast, thyroid and male testis were the most common cancers across countries followed by melanoma of skin and cancers of the cervix. Variations in cancer incidence rates across different populations may reflect different distribution of risk factors, variations in the implementation or uptake of screening as well as overdiagnosis. AYA cancer mortality disparities may be due to variation in early-stage diagnoses, different public education and awareness of cancer symptoms, different degrees of access or availability of treatment.Conclusions:Our results highlight the future health care needs and requirements for AYA-specialised services to ensure a homogeneous treatment across different countries as well as the urgency for preventive initiatives that can mitigate the increasing burden. &nbsp

Background There has been a noticeable annual increase in the number of children coming to Italy for medical treatment, just like it has happened in the rest of the European Union. In Italy, the assistance to children suffering from cancer is assured by the current network of 54 centres members of the Italian Association of Paediatric Haematology and Oncology (AIEOP), which has kept records of all demographic and clinical data in the database of Mod.1.01 Registry since 1989. Methods We used the information stored in the already mentioned database to assess the impact of immigration of foreign children with cancer on centres' activity, with the scope of drawing a map of the assistance to these cases. Results Out of 14,738 cases recorded by all centres in the period from 1999 to 2008, 92.2% were born and resident in Italy, 4.1% (608) were born abroad and living abroad and 3.7% (538) were born abroad and living in Italy. Foreign children cases have increased over the years from 2.5% in 1999 to. 8.1% in 2008. Most immigrant children came from Europe (65.7%), whereas patients who came from America, Asia and Oceania amounted to 13.2%, 10.1%, 0.2%, respectively. The immigrant survival rate was lower compared to that of children who were born in Italy. This is especially true for acute lymphoblastic leukaemia patients entered an AIEOP protocol, who showed a 10-years survival rate of 71.0% vs. 80.7% (p < 0.001) for immigrants and patients born in Italy, respectively. Conclusions Children and adolescents are an increasingly important part of the immigration phenomenon, which occurs in many parts of the world. In Italy the vast majority of children affected by malignancies are treated in AIEOP centres. Since immigrant children are predominantly treated in northern Italy, these centres have developed a special expertise in treating immigrant patients, which is certainly very useful for the entire AIEOP network.

Despite the success in treating the majority of children with newly diagnosed acute leukemia, children with relapsed or refractory disease are an exceptionally difficult group of patients to cure. We assessed the combination of fludarabine with cytarabine and granulocyte colony-stimulating factor (FLAG) and non-pegylated liposomal doxorubicin (Myocet) in children with either acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) refractory to first-line therapy or who had relapsed after risk-tailored chemotherapy. We treated 35 patients with FLAG-Myocet. The median age at treatment was 9 years and 7 months (range, 1 to 18 y). The 94% of ALL patients (16/17) and the 61% AML patients (11/18) achieved complete remission after FLAG-Myocet. A partial response was observed in the 17% of AML patients (3/18). Twenty-eight of 35 (80%) patients received hematopoetic stem cell transplantation in remission induced by FLAG-Myocet regimen. The ALL and AML overall survival at 3 years after FLAG-Myocet is 33% and 38%, respectively. The probability of ALL and AML event-free survival at 3 years after FLAG-Myocet is 33% and 40%, respectively. The probability of ALL and AML disease-free survival at 3 years after hematopoietic stem cell transplantation is 19% and 58%, respectively. Non-hematological toxicity was remarkably low, while almost all patients showed severe hematological toxicity. FLAG-Myocet is an efficient and a well-tolerated regimen that allows nearly all patients to undergo hematopoetic stem cell transplantation. FLAG-Myocet proved to be safe in terms of acute cardiac toxicity although particular care must be taken to reduce infectious complications due to severe myelosuppression. The promising results shown in our study need to be confirmed by larger and possibly randomized trials.