@article {10797, title = {Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry.}, journal = {Am J Hematol}, volume = {94}, year = {2019}, month = {2019 Feb}, pages = {216-222}, abstract = {

Autoimmune neutropenia of infancy (AIN) is characterized by low risk of severe infection, tendency to spontaneously resolve and typically onset at <=4-5 years of age; it is due to auto-antibodies whose detection is often difficult. In case of negativity of 4 antineutrophils autoantibody tests, after having excluded ethnic, postinfection, drug induced, or congenital neutropenia, according to the Italian guidelines the patients will be defined as affected by "idiopathic neutropenia" (IN). We describe the characteristics of 85 IN patients enrolled in the Italian neutropenia registry: they were compared with 336 children affected by AIN. The 2 groups were clinically very similar and the main differences were detection age (later in IN), length of disease (longer in IN) and, among recovered patients, age of spontaneous recovery: the median age at resolution was 2.13 years in AINs and 3.03 years in INs (P = .00002). At bivariate analysis among AIN patients earlier detection age (P = .00013), male sex (P = .000748), absence of leucopenia (P = .0045), and absence of monocytosis (P = .0419) were significantly associated with earlier recovery; in the IN group only detection age (P = .013) and absence of monocytosis (P = .0333) were significant. At multivariate analysis detection age and absence of monocytosis were independently significant (P = 6.7e-05 and 4.4e-03, respectively) in the AIN group, whereas in the IN group only detection age stayed significant (P = .013).

}, issn = {1096-8652}, doi = {10.1002/ajh.25353}, author = {Farruggia, Piero and Fioredda, Francesca and Puccio, Giuseppe and Onofrillo, Daniela and Russo, Giovanna and Barone, Angelica and Bonanomi, Sonia and Boscarol, Gianluca and Finocchi, Andrea and Ghilardi, Roberta and Giordano, Paola and Ladogana, Saverio and Lassandro, Giuseppe and Luti, Laura and Lanza, Tiziana and Mandaglio, Rosalba and Marra, Nicoletta and Martire, Baldassare and Mastrodicasa, Elena and Motta, Milena and Notarangelo, Lucia Dora and Pillon, Marta and Porretti, Laura and Serafinelli, Jessica and Trizzino, Angela and Tucci, Fabio and Veltroni, Marinella and Verzegnassi, Federico and Ramenghi, Ugo and Dufour, Carlo} } @article {10421, title = {Hypomorphic FANCA mutations correlate with mild mitochondrial and clinical phenotype in Fanconi anemia.}, journal = {Haematologica}, volume = {103}, year = {2018}, month = {2018 Mar}, pages = {417-426}, abstract = {

Fanconi anemia is a rare disease characterized by congenital malformations, aplastic anemia, and predisposition to cancer. Despite the consolidated role of the Fanconi anemia proteins in DNA repair, their involvement in mitochondrial function is emerging. The purpose of this work was to assess whether the mitochondrial phenotype, independent of genomic integrity, could correlate with patient phenotype. We evaluated mitochondrial and clinical features of 11 affected individuals homozygous or compound heterozygous for p.His913Pro and p.Arg951Gln/Trp, the two residues of FANCA that are more frequently affected in our cohort of patients. Although p.His913Pro and p.Arg951Gln proteins are stably expressed in cytoplasm, they are unable to migrate in the nucleus, preventing cells from repairing DNA. In these cells, the electron transfer between respiring complex I-III is reduced and the ATP/AMP ratio is impaired with defective ATP production and AMP accumulation. These activities are intermediate between those observed in wild-type and FANCA-/- cells, suggesting that the variants at residues His913 and Arg951 are hypomorphic mutations. Consistent with these findings, the clinical phenotype of most of the patients carrying these mutations is mild. These data further support the recent finding that the Fanconi anemia proteins play a role in mitochondria, and open up possibilities for genotype/phenotype studies based on novel mitochondrial criteria.

}, issn = {1592-8721}, doi = {10.3324/haematol.2017.176131}, author = {Bottega, Roberta and Nicchia, Elena and Cappelli, Enrico and Ravera, Silvia and De Rocco, Daniela and Faleschini, Michela and Corsolini, Fabio and Pierri, Filomena and Calvillo, Michaela and Russo, Giovanna and Casazza, Gabriella and Ramenghi, Ugo and Farruggia, Piero and Dufour, Carlo and Savoia, Anna} } @article {10525, title = {Autoimmune neutropenia of childhood secondary to other autoimmune disorders: Data from the Italian neutropenia registry.}, journal = {Am J Hematol}, volume = {92}, year = {2017}, month = {2017 Sep}, pages = {E546-E549}, keywords = {Autoimmune Diseases, Child, Disease Susceptibility, Female, Humans, Immunoglobulins, Intravenous, Immunosuppressive Agents, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Italy, Male, Neutropenia, Prevalence, Registries}, issn = {1096-8652}, doi = {10.1002/ajh.24803}, author = {Farruggia, Piero and Puccio, Giuseppe and Fioredda, Francesca and Lanza, Tiziana and Porretti, Laura and Ramenghi, Ugo and Barone, Angelica and Bonanomi, Sonia and Finocchi, Andrea and Ghilardi, Roberta and Ladogana, Saverio and Marra, Nicoletta and Martire, Baldassare and Notarangelo, Lucia Dora and Onofrillo, Daniela and Pillon, Marta and Russo, Giovanna and Lo Valvo, Laura and Serafinelli, Jessica and Tucci, Fabio and Zunica, Fiammetta and Verzegnassi, Federico and Dufour, Carlo} } @article {10539, title = {Diagnosis and management of newly diagnosed childhood autoimmune haemolytic anaemia. Recommendations from the Red Cell Study Group of the Paediatric Haemato-Oncology Italian Association.}, journal = {Blood Transfus}, volume = {15}, year = {2017}, month = {2017 May}, pages = {259-267}, abstract = {

Autoimmune haemolytic anaemia is an uncommon disorder to which paediatric haematology centres take a variety of diagnostic and therapeutic approaches. The Red Cell Working Group of the Italian Association of Paediatric Onco-haematology (Associazione Italiana di Ematologia ed Oncologia Pediatrica, AIEOP) developed this document in order to collate expert opinions on the management of newly diagnosed childhood autoimmune haemolytic anaemia.The diagnostic process includes the direct and indirect antiglobulin tests; recommendations are given regarding further diagnostic tests, specifically in the cases that the direct and indirect antiglobulin tests are negative. Clear-cut definitions of clinical response are stated. Specific recommendations for treatment include: dosage of steroid therapy and tapering modality for warm autoimmune haemolytic anaemia; the choice of rituximab as first-line therapy for the rare primary transfusion-dependent cold autoimmune haemolytic anaemia; the indications for supportive therapy; the need for switching to second-line therapy. Each statement is provided with a score expressing the level of appropriateness and the agreement among participants.

}, keywords = {Anemia, Hemolytic, Autoimmune, Blood Transfusion, Child, Coombs Test, Disease Management, Hematology, Humans, Immunoglobulin M, Italy, Pediatrics, Societies, Medical, Steroids}, issn = {1723-2007}, doi = {10.2450/2016.0072-16}, author = {Ladogana, Saverio and Maruzzi, Matteo and Samperi, Piera and Perrotta, Silverio and Del Vecchio, Giovanni C and Notarangelo, Lucia D and Farruggia, Piero and Verzegnassi, Federico and Masera, Nicoletta and Saracco, Paola and Fasoli, Silvia and Miano, Maurizio and Girelli, Gabriella and Barcellini, Wilma and Zanella, Alberto and Russo, Giovanna} } @article {8286, title = {The prognostic value of biological markers in paediatric Hodgkin lymphoma.}, journal = {Eur J Cancer}, volume = {52}, year = {2016}, month = {2016 Jan}, pages = {33-40}, abstract = {

BACKGROUND: Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children.

PATIENTS AND METHODS: By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens.

RESULTS: On multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography.

CONCLUSION: Using the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes.

}, keywords = {Adolescent, Age Factors, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Blood Platelets, Child, Child, Preschool, Databases, Factual, Disease Progression, Disease-Free Survival, Eosinophils, Female, Ferritins, Hodgkin Disease, Humans, Infant, Infant, Newborn, Italy, Kaplan-Meier Estimate, Leukocyte Count, Male, Multivariate Analysis, Neoplasm Staging, Platelet Count, Predictive Value of Tests, Proportional Hazards Models, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome}, issn = {1879-0852}, doi = {10.1016/j.ejca.2015.09.003}, author = {Farruggia, Piero and Puccio, Giuseppe and Sala, Alessandra and Todesco, Alessandra and Buffardi, Salvatore and Garaventa, Alberto and Bottigliero, Gaetano and Bianchi, Maurizio and Zecca, Marco and Locatelli, Franco and Pession, Andrea and Pillon, Marta and Favre, Claudio and D{\textquoteright}Amico, Salvatore and Provenzi, Massimo and Trizzino, Angela and Zanazzo, Giulio Andrea and Sau, Antonella and Santoro, Nicola and Murgia, Giulio and Casini, Tommaso and Mascarin, Maurizio and Burnelli, Roberta} } @article {8327, title = {Somatic, hematologic phenotype, long-term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Associ}, journal = {Am J Hematol}, volume = {91}, year = {2016}, month = {2016 Jul}, pages = {666-71}, abstract = {

We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy-two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow-up, 33\% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6\% with median follow-up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666-671, 2016. {\textcopyright} 2016 Wiley Periodicals, Inc.

}, issn = {1096-8652}, doi = {10.1002/ajh.24373}, author = {Svahn, Johanna and Bagnasco, Francesca and Cappelli, Enrico and Onofrillo, Daniela and Caruso, Silvia and Corsolini, Fabio and De Rocco, Daniela and Savoia, Anna and Longoni, Daniela and Pillon, Marta and Marra, Nicoletta and Ramenghi, Ugo and Farruggia, Piero and Locasciulli, Anna and Addari, Carmen and Cerri, Carla and Mastrodicasa, Elena and Casazza, Gabriella and Verzegnassi, Federico and Riccardi, Francesca and Haupt, Riccardo and Barone, Angelica and Cesaro, Simone and Cugno, Chiara and Dufour, Carlo} } @article {7760, title = {Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort.}, journal = {Br J Haematol}, volume = {169}, year = {2015}, month = {2015 May}, pages = {584-9}, abstract = {

Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25{\textperiodcentered}8\%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74{\textperiodcentered}2\%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of non-clonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment.

}, keywords = {Adolescent, Adult, Amino Acid Substitution, Child, Child, Preschool, Cohort Studies, Female, Hematologic Neoplasms, Humans, Infant, Janus Kinase 2, Male, Mutation, Missense, Neoplasm Proteins, Thrombocythemia, Essential}, issn = {1365-2141}, doi = {10.1111/bjh.13329}, author = {Randi, Maria L and Geranio, Giulia and Bertozzi, Irene and Micalizzi, Concetta and Ramenghi, Ugo and Tucci, Fabio and Notarangelo, Lucia D and Ladogana, Saverio and Menna, Giuseppe and Giordano, Paola and Consarino, Caterina and Farruggia, Piero and Zanazzo, Giulio A and Fiori, Giovanni M and Burnelli, Roberta and Russo, Giovanna and Jankovich, Momcilo and Peroni, Edoardo and Duner, Elena and Basso, Giuseppe and Fabris, Fabrizio and Putti, Maria C} } @article {3549, title = {Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology.}, journal = {Haematologica}, volume = {99}, year = {2014}, month = {2014 Jun}, pages = {1022-31}, abstract = {

Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26\% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes.

}, keywords = {Amino Acid Substitution, Cell Line, Cohort Studies, Computational Biology, Databases, Nucleic Acid, Fanconi Anemia, Fanconi Anemia Complementation Group Proteins, Founder Effect, Genotype, Humans, Italy, Mosaicism, Mutation, Polymorphism, Single Nucleotide}, issn = {1592-8721}, doi = {10.3324/haematol.2014.104224}, author = {De Rocco, Daniela and Bottega, Roberta and Cappelli, Enrico and Cavani, Simona and Criscuolo, Maria and Nicchia, Elena and Corsolini, Fabio and Greco, Chiara and Borriello, Adriana and Svahn, Johanna and Pillon, Marta and Mecucci, Cristina and Casazza, Gabriella and Verzegnassi, Federico and Cugno, Chiara and Locasciulli, Anna and Farruggia, Piero and Longoni, Daniela and Ramenghi, Ugo and Barberi, Walter and Tucci, Fabio and Perrotta, Silverio and Grammatico, Paola and Hanenberg, Helmut and Della Ragione, Fulvio and Dufour, Carlo and Savoia, Anna} }