Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network.

Severe combined immunodeficiencies (SCIDs) are a group of inborn errors of the immune system, usually associated with severe or life-threatening infections. Due to the variability of clinical phenotypes, the diagnostic complexity and the heterogeneity of the genetic basis, they are often difficult to recognize, leading to a significant diagnostic delay (DD). Aim of this study is to define presenting signs and natural history of SCID in a large cohort of patients, prior to hematopoietic stem cell or gene therapies.

Mesenchymal stromal cells from Shwachman-Diamond syndrome patients fail to recreate a bone marrow niche in vivo and exhibit impaired angiogenesis.

Shwachman-Diamond syndrome (SDS) is a rare multi-organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood.

Pediatric extraspinal sacrococcygeal ependymoma (ESE): an Italian AIEOP experience of six cases and literature review.

Background: Primary pediatric extraspinal sacrococcygeal ependymoma (ESE) is a very rare disease, poorly described in literature, whose diagnostic, therapeutic, and follow-up approach is still controversial.

Methods: We describe six cases of pediatric ESE treated at Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers in Italy since 1983, with a review of the literature.

Results: All six patients had primary sacrococcygeal disease (two presacral and four subcutaneous) with median age of 10 years.

Primary mediastinal large B-cell lymphoma: Outcome of a series of pediatric patients treated with high-dose methotrexate and cytarabine plus anti-CD20.

Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B-cell lymphoma (PMLBL) were treated according to a modified version of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) LNH-97 protocol based on high-dose methotrexate, anthracyclines, and addition of anti-CD20. Ten patients achieved a continuous complete remission with front-line therapy. The overall 5-year survival was 91.

Detection of prognostic factors in children and adolescents with Burkitt and Diffuse Large B-Cell Lymphoma treated with the AIEOP LNH-97 protocol.

Burkitt lymphoma (BL) and Diffuse Large B-Cell Lymphoma (DLBCL) account for most cases of non-Hodgkin lymphoma (NHL) in childhood. We report the clinical characteristics, outcome and prognostic factors in children with BL or DLBCL treated according to the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) LNH-97 protocol. Patients aged up to 18 years that were newly diagnosed with BL/DLBCL were included in the study.

Early T-cell precursor acute lymphoblastic leukaemia in children treated in AIEOP centres with AIEOP-BFM protocols: a retrospective analysis.

Background: Early T-cell precursor acute lymphoblastic leukaemia was recently recognised as a distinct leukaemia and reported as associated with poor outcomes. We aimed to assess the outcome of early T-cell precursor acute lymphoblastic leukaemia in patients from the Italian Association of Pediatric Hematology Oncology (AIEOP) centres treated with AIEOP-Berlin-Frankfurt-Münster (AIEOP-BFM) protocols.

Methods: In this retrospective analysis, we included all children aged from 1 to less than 18 years with early T-cell precursor acute lymphoblastic leukaemia immunophenotype diagnosed between Jan 1, 2008, and Oct 31, 2014, from AIEOP centres.

Non-Hodgkin lymphoma in children with an associated inherited condition: A retrospective analysis of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

Background: Inherited conditions affecting genetic aberration, viral oncogenesis, reduced immune surveillance, and long-lasting antigen stimulation may build the way to lymphomagenesis in humans.

Methods: We extracted from the database of 4 consecutive trials for pediatric non-Hodgkin lymphoma (NHL) all cases with an associated genetic disease.

Results: Among 1,430 patients, 34 (2.

Cutaneous melanoma in children and adolescents: the Italian rare tumors in pediatric age project experience.

Objective: To describe a series of cutaneous melanoma in children collected by the Italian Rare Tumors in Pediatric Age project.

Study Design: From 2000 to 2012, 54 patients younger than 18 years of age were prospectively registered and treated at 12 Italian pediatric centers on the basis of the same diagnostic/therapeutic recommendations and with the same forms to record clinical data.

Results: Considering the estimated annual incidence in Italy, the registered cases accounted for 30% of those expected in children and 10% of adolescents.

Metastatic renal cell carcinoma in children and adolescents: a 30-year unsuccessful story.

Background: Because of the rare occurrence of renal cell carcinoma (RCC) among children very little is known about this malignancy in pediatric age. We aimed adding knowledge on the clinical characteristics and outcome of metastatic (m) RCC in children and adolescents.

Patients And Methods: The series included 14 stage 4 RCC patients with a median age at diagnosis of 155.

Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 deficiency: novel genotypes and phenotypic variability in severe congenital neutropenia.

Objective: To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3).

Study Design: Patients with syndromic SCN were characterized for associated malformations and referred to us for G6PC3 mutational analysis.

Results: In a cohort of 31 patients with syndromic SCN, we identified 16 patients with G6PC3 deficiency including 11 patients with novel biallelic mutations.

A case of syndromic neutropenia and mutation in G6PC3.

Background: A previously unrecognized syndrome with congenital neutropenia and various organ abnormalities has been described recently, caused by mutations in the gene encoding glucose-6-phosphatase, catalytic subunit 3 (G6PC3).

Observation: A 10-year-old boy from Ecuador suffering from severe neutropenia and multiple nonhematopoietic abnormalities was admitted to our department. We identified a novel mutation in the G6PC3 gene (c.

Clinical features, long-term follow-up and outcome of a large cohort of patients with Chronic Granulomatous Disease: an Italian multicenter study.

A retrospective clinical and immunological survey was conducted in 60 patients with Chronic Granulomatous Disease. A prospective controlled non-randomized study of the efficacy of long-term IFNgamma treatment was carried out. The mean age at the time of diagnosis was 4.

Prognostic role of minimal residual disease in mature B-cell acute lymphoblastic leukemia of childhood.

Purpose: To study the prevalence of t(8;14) at diagnosis and the response kinetics to treatment of minimal residual disease (MRD) in B-cell acute lymphoblastic leukemia (B-ALL) patients and determine its impact on prognosis.

Patients And Methods: A total of 68 children affected by de novo B-ALL enrolled onto the Berlin-Frankfurt-Muenster-based Italian Association of Pediatric Hematology and Oncology LNH-97 clinical protocol were studied. Bone marrow aspirate from each patient was analyzed for the presence of t(8;14)(q24;q32) by long-distance polymerase chain reaction at diagnosis, after the first chemotherapy cycle, and after subsequent cycles until negative for MRD.

Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia.

Autosomal-recessive agammaglobulinemia is a rare and heterogeneous disorder, characterized by early-onset infections, profound hypogammaglobulinemia of all immunoglobulin isotypes and absence of circulating B lymphocytes. To investigate the molecular basis of the disease, 23 patients with early-onset disease and no mutations in Bruton tyrosine kinase, the gene responsible for X-linked agammaglobulinemia, were selected and analyzed by direct sequencing of candidate genes. Two novel mutations in the mu heavy chain (muHC) gene (IGHM) were identified in three patients belonging to two unrelated families.

Soft-tissue sarcomas in children and adolescents with neurofibromatosis type 1.

Background: Patients affected by neurofibromatosis type 1 (NF1) are at higher risk of developing soft-tissue sarcomas (STS) than the general population. The clinical findings and outcome in 43 children and adolescents with NF1 treated for STS in the Italian protocols between 1988 and 2004 are reported.

Methods: The study included 37 patients with neurogenic sarcomas (36 malignant peripheral nerve sheath tumors [MPNST], 1 triton tumor) and 6 cases of rhabdomyosarcoma (RMS).

Conservative management of hyperplastic and multicentric nephroblastomatosis.

Purpose: The treatment of hyperplastic nephroblastomatosis remains controversial. We report the advantages of conservative management of hyperplastic and multicentric nephroblastomatosis associated with unilateral Wilms tumor (WT).

Materials And Methods: During the last 10 years 48 children with unilateral WT were consecutively treated at our 2 institutions.

Familial platelet disorder with propensity to acute myelogenous leukemia: genetic heterogeneity and progression to leukemia via acquisition of clonal chromosome anomalies.

Familial platelet disorder with propensity to acute myelogenous leukemia, or FPD/AML (OMIM #601399), is a rare autosomal dominant condition, with only 12 families reported. It is characterized by qualitative and quantitative platelet defects and predisposition to the development of myeloid malignancies. Causal mutations have been identified in the RUNX1 gene (also known as AML1, CBFA2) in the 11 families so far analyzed.

Renal cell carcinoma in children: a clinicopathologic study.

Purpose: To identify the prognostic factors, treatment, and outcome of children affected by renal cell carcinoma (RCC).

Patients And Methods: The series included 41 patients (18 males and 23 females) with a median age of 124 months observed at the 11 Italian Association for Pediatric Hematology and Oncology centers from January 1973 to January 2001. Clinical data, surgical notes, pathologic findings, and summaries of therapy were taken from the charts.

Rituximab for the treatment of refractory autoimmune hemolytic anemia in children.

Autoimmune hemolytic anemia (AIHA) in children is sometimes characterized by a severe course, requiring prolonged administration of immunosuppressive therapy. Rituximab is able to cause selective in vivo destruction of B lymphocytes, with abrogation of antibody production. In a prospective study, we have evaluated the use of rituximab for the treatment of AIHA resistant to conventional treatment.

Characterization of oligosaccharides in milk and feces of breast-fed infants by high-performance anion-exchange chromatography.

Human milk contains a large amount of oligosaccharides, which represent its third largest solute. Nevertheless, both the metabolism and the role of these substances are still largely unknown. A previous study we conducted documented that the amount of oligosaccharides excreted in the feces varies from 6% to 13% of the 24-hour ingested oligosaccharides.

Oligosaccharides in human milk during different phases of lactation.

Twenty-one oligosaccharides of human milk were quantified by high-performance anion-exchange chromatography. Milk samples were collected from 18 mothers during the first 3 mo of lactation. The data show that the highest amount of all oligosaccharides is present at day 4 postpartum (20 g l(-1)) and then decreases by about 20% at day 30 of lactation.