@article {10526, title = {Retrospective study on the incidence and outcome of proven and probable invasive fungal infections in high-risk pediatric onco-hematological patients.}, journal = {Eur J Haematol}, volume = {99}, year = {2017}, month = {2017 Sep}, pages = {240-248}, abstract = {

BACKGROUND: Invasive fungal infection (IFI) is a cause of morbidity, mortality and increased health costs in children undergoing chemotherapy or hematopoietic stem cell transplant (HSCT).

METHODS: Multicenter, retrospective study to assess the incidence, outcome of proven and probable IFI (PP-IFI) in children treated for acute leukemia, non-Hodgkin lymphoma or who underwent HSCT from 2006 to 2012.

RESULTS: Over the 7-year period, 127 PP-IFI were diagnosed in 123 patients, median age of 9.7~years. The 1-year cumulative incidence was 2.5\% (CI 1.8-3.7) after frontline chemotherapy, 9.4\% (CI 5.8-15.0) after relapse, and 5.3\% (CI 3.9-7.1) after HSCT. Severe neutropenia was present in 98 (77\%) patients. Culture-proven agents were Candida spp., mostly non-albicans, 28, mold 23, whereas three proven IFI were identified by histopathology. Favorable response to treatment within 3~months from diagnosis was observed in 77 (89\%). The overall ninety-day probability of survival was 68\% (CI 59-76).

CONCLUSIONS: About two-thirds of pediatric patients with PP-IFI survived, regardless of whether the infection occurred after frontline chemotherapy, reinduction chemotherapy for disease relapse, or after HSCT. Further prospective studies are needed to define the impact of antifungal prophylaxis and early combination therapy on short-term overall survival.

}, keywords = {Adolescent, Antifungal Agents, Antineoplastic Combined Chemotherapy Protocols, Child, Child, Preschool, Drug Therapy, Combination, Female, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Incidence, Male, Mycoses, Patient Outcome Assessment, Retrospective Studies, Survival Analysis, Treatment Outcome}, issn = {1600-0609}, doi = {10.1111/ejh.12910}, author = {Cesaro, Simone and Tridello, Gloria and Castagnola, Elio and Calore, Elisabetta and Carraro, Francesca and Mariotti, Ilaria and Colombini, Antonella and Perruccio, Katia and Decembrino, Nunzia and Russo, Giovanna and Maximova, Natalia and Baretta, Valentina and Caselli, D{\'e}sir{\'e}e} } @article {8350, title = {Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome.}, journal = {Sci Rep}, volume = {6}, year = {2016}, month = {2016}, pages = {25441}, abstract = {

Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca(2+)]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials.

}, issn = {2045-2322}, doi = {10.1038/srep25441}, author = {Ravera, Silvia and Dufour, Carlo and Cesaro, Simone and Bottega, Roberta and Faleschini, Michela and Cuccarolo, Paola and Corsolini, Fabio and Usai, Cesare and Columbaro, Marta and Cipolli, Marco and Savoia, Anna and Degan, Paolo and Cappelli, Enrico} } @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 {3618, title = {Central venous access devices in pediatric malignancies: a position paper of Italian Association of Pediatric Hematology and Oncology.}, journal = {J Vasc Access}, volume = {16}, year = {2015}, month = {2015 Mar-Apr}, pages = {130-6}, abstract = {

INTRODUCTION: Treatment of pediatric malignancies is becoming progressively more complex, implying the adoption of multimodal therapies. A reliable, long-lasting venous access represents one of the critical requirements for the success of those treatments. Recent technical innovations-such as minimally invasive procedures for placement, new devices and novel materials-have rapidly spread for clinical use in adult patients, but are still not consistently used in the pediatric population.

METHODS: The Supportive Therapy Working Group of Italian Association of Hematology and Oncology (AIEOP) reviewed medical literature focusing on new aspects of central venous access devices (VADs) in pediatric patients affected by oncohematological diseases.

RESULTS: Appropriate recommendations for clinical use in these patients have been discussed and formulated.

CONCLUSIONS: The importance of the correct choice, management and use of VADs in pediatric oncohematological patients is a necessary prerequisite for an adequate standard of care, also considering the increased chances of cure and the longer life expectancy of those patients with modern therapies.

}, issn = {1724-6032}, doi = {10.5301/jva.5000314}, author = {Crocoli, Alessandro and Tornesello, Assunta and Pittiruti, Mauro and Barone, Angelica and Muggeo, Paola and Inserra, Alessandro and Molinari, Angelo Claudio and Grillenzoni, Valeria and Durante, Viviana and Cicalese, Maria Pia and Zanazzo, Giulio Andrea and Cesaro, Simone} } @article {8026, title = {Recommendations for the use of long-term central venous catheter (CVC) in children with hemato-oncological disorders: management of CVC-related occlusion and CVC-related thrombosis. On behalf of the coagulation defects working group and the supportive the}, journal = {Ann Hematol}, volume = {94}, year = {2015}, month = {2015 Nov}, pages = {1765-76}, abstract = {

Central venous catheters (CVC), used for the management of children with hemato-oncological disorders, are burdened by a significant incidence of mechanical, infective, or thrombotic complications. These complications favor an increasing risk in prolongation of hospitalization, extra costs of care, and sometimes severe life-threatening events. No guidelines for the management of CVC-related occlusion and CVC-related thrombosis are available for children. To this aim, members of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) reviewed the pediatric and adult literature to propose the first recommendations for the management of CVC-related occlusion and CVC-related thrombosis in children with hemato-oncological disorders.

}, keywords = {Adult, Blood Coagulation Disorders, Catheter Obstruction, Catheterization, Central Venous, Central Venous Catheters, Child, Hematologic Neoplasms, Humans, Risk Factors, Thrombosis}, issn = {1432-0584}, doi = {10.1007/s00277-015-2481-1}, author = {Giordano, Paola and Saracco, Paola and Grassi, Massimo and Luciani, Matteo and Banov, Laura and Carraro, Francesca and Crocoli, Alessandro and Cesaro, Simone and Zanazzo, Giulio Andrea and Molinari, Angelo Claudio} } @article {3608, title = {Single-day trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis pneumonia in children with cancer.}, journal = {J Pediatr}, volume = {164}, year = {2014}, month = {2014 Feb}, pages = {389-92.e1}, abstract = {

OBJECTIVE: To determine whether a simplified, 1-day/week regimen of trimethoprim/sulfamethoxazole is sufficient to prevent Pneumocystis (jirovecii [carinii]) pneumonia (PCP). Current recommended regimens for prophylaxis against PCP range from daily administration to 3 consecutive days per week dosing.

STUDY DESIGN: A prospective survey of the regimens adopted for the PCP prophylaxis in all patients treated for childhood cancer at pediatric hematology-oncology centers of the Associazione Italiana Ematologia Oncologia Pediatrica.

RESULTS: The 20 centers participating in the study reported a total of 2466 patients, including 1093 with solid tumor and 1373 with leukemia/lymphoma (or primary immunodeficiency; n = 2). Of these patients, 1371 (55.6\%) received the 3-day/week prophylaxis regimen, 406 (16.5\%) received the 2-day/week regimen, and 689 (27.9\%), including 439 with leukemia/lymphoma, received the 1-day/week regimen. Overall, only 2 cases of PCP (0.08\%) were reported, both in the 2-day/week group. By intention to treat, the cumulative incidence of PCP at 3 years was 0.09\% overall (95\% CI, 0.00-0.40\%) and 0.51\% for the 2-day/week group (95\% CI, 0.10\%-2.00\%). Remarkably, both patients who failed had withdrawn from prophylaxis.

CONCLUSION: A single-day course of prophylaxis with trimethoprim/sulfamethoxazole may be sufficient to prevent PCP in children with cancer undergoing intensive chemotherapy regimens. This simplified strategy might have implications for the emerging need for PCP prophylaxis in other patients subjected to the increased use of biological and nonbiological agents that induce higher levels of immune suppression, such as those with rheumatic diseases.

}, keywords = {Anti-Infective Agents, Child, Dose-Response Relationship, Drug, Drug Administration Schedule, Follow-Up Studies, Hematologic Neoplasms, Humans, Incidence, Italy, Pneumocystis carinii, Pneumonia, Pneumocystis, Prospective Studies, Treatment Outcome, Trimethoprim, Sulfamethoxazole Drug Combination}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2013.10.021}, author = {Caselli, D{\'e}sir{\'e}e and Petris, Maria Grazia and Rondelli, Roberto and Carraro, Francesca and Colombini, Antonella and Muggeo, Paola and Ziino, Ottavio and Melchionda, Fraia and Russo, Giovanna and Pierani, Paolo and Soncini, Elena and DeSantis, Raffaella and Zanazzo, Giulio and Barone, Angelica and Cesaro, Simone and Cellini, Monica and Mura, Rossella and Milano, Giuseppe M and Meazza, Cristina and Cicalese, Maria P and Tropia, Serena and De Masi, Salvatore and Castagnola, Elio and Aric{\`o}, Maurizio} } @article {1834, title = {Glutamine-enriched nutrition does not reduce mucosal morbidity or complications after stem-cell transplantation for childhood malignancies: a prospective randomized study.}, journal = {Transplantation}, volume = {91}, year = {2011}, month = {2011 Jun 27}, pages = {1321-5}, abstract = {

BACKGROUND: Intravenous glutamine-enriched solution seems to be effective in posttransplant period in decreasing the severity and duration of mucositis. The aim of this randomized study was to determine the benefit of glutamine supplementation both on mucosal morbidity and in posttransplant associated complications.

METHODS: Children undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) for malignant hematological diseases were randomly assigned to standard total parenteral nutrition (S-TPN) or glutamine-enriched (GE)-TPN solution consisting of 0.4 g/kg/day of l-alanine-glutamine dipeptide. This treatment started on the day of HSCT and ended when the patients could orally cover more than 50\% of their daily energy requirements. The severity and the rate of post-HSCT mucositis were based on World Health Organization criteria. All the analyses were conducted on intention-to-treat principle.

RESULTS: One hundred twenty consecutive patients (83 men; median age, 8.1 years) were enrolled. The mean duration of treatment was 23.5 and 23 days in the two treatment arms. The mean calorie intake was 1538 kcal/d in the S-TPN group and 1512 kcal/d in GE-TPN group. All patients were well nourished before and after HSCT. Mucositis occurred in 91.4\% and 91.7\% of patients in S-TPN and GE-TPN arm, respectively (P=0.98). Odds ratio adjusted by type of HSCT was 0.98 (95\% confidence interval, 0.26-2.63). Type and duration of analgesic treatment, clinical outcome (engraftment, graft versus host disease, early morbidity, and mortality, relapse rate up to 180 days post-HSCT) were not significantly different in the two treatment arms.

CONCLUSION: GE-TPN solution does not affect mucositis and outcome in well-nourished HSCT allogeneic patients.

}, keywords = {Adolescent, Analgesia, Child, Child, Preschool, Double-Blind Method, Female, Glutamine, Hematopoietic Stem Cell Transplantation, Humans, Infant, Male, Mucositis, Mucous Membrane, Neoplasms, Odds Ratio, Parenteral Nutrition, Prospective Studies, Recurrence, Stem Cells, Treatment Outcome}, issn = {1534-6080}, doi = {10.1097/TP.0b013e31821ab959}, author = {Uderzo, Cornelio and Rebora, Paola and Marrocco, Emanuela and Varotto, Stefania and Cichello, Francesca and Bonetti, Maurizio and Maximova, Natalia and Zanon, Davide and Fagioli, Franca and Nesi, Francesca and Masetti, Riccardo and Masetti, Roberto and Rovelli, Attilio and Rondelli, Roberto and Valsecchi, Maria Grazia and Cesaro, Simone} } @article {1745, title = {A Phase II study on the safety and efficacy of a single dose of pegfilgrastim for mobilization and transplantation of autologous hematopoietic stem cells in pediatric oncohematology patients.}, journal = {Transfusion}, volume = {51}, year = {2011}, month = {2011 Nov}, pages = {2480-7}, abstract = {

BACKGROUND: Limited data are available on the use of pegfilgrastim in pediatric patients as a mobilizing agent in association with chemotherapy.

STUDY DESIGN AND METHODS: This was a prospective, multicenter, Phase II study to evaluate the safety and efficacy of a single dose of 100 {\textmu}g/kg pegfilgrastim in mobilizing peripheral blood stem cells (PBSCs) in pediatric patients. The primary endpoint of the study was the percentage of good mobilizers with pegfilgrastim (blood peak of CD34+ cells >= 20 {\texttimes} 10(6) /L). The results were compared with a historical control group.

RESULTS: Thirty of 36 recruited patients were classified as good mobilizers (83\%). The median value of circulating CD34+ at leukapheresis was 143 {\texttimes} 10(6) /L (range, 20 {\texttimes} 10(6) -1988 {\texttimes} 10(6) /L). No significant adverse effects were associated with the use of pegfilgrastim and no patient was withdrawn from using the drug. A blood peak of 20 {\texttimes} 10(6) /L or more CD34+ was observed in 33 of 36 control patients (92\%) and the median CD34+ count at leukapheresis was 158 {\texttimes} 10(6) /kg (range, 28 {\texttimes} 10(6) -4529 {\texttimes} 10(6) /kg; p = 0.7). No significant differences were found between the two groups in terms of toxicity or other variables of mobilization. As at October 2008, 23 patients of the pegfilgrastim group and 32 patients of the filgrastim group underwent autologous transplant. No significant differences were found in terms of early toxicity, myeloid recovery, and Day 100 survival.

CONCLUSION: A single dose of 100 {\textmu}g/kg pegfilgrastim was safe and effective for PBSC collection in pediatric patients. We suggest that these results support the use of pegfilgrastim for pediatric patients.

}, keywords = {Adolescent, Adult, Child, Child, Preschool, Female, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cell Mobilization, Humans, Infant, Male, Neoplasms, Peripheral Blood Stem Cell Transplantation, Prospective Studies, Recombinant Proteins, Transplantation, Autologous}, issn = {1537-2995}, doi = {10.1111/j.1537-2995.2011.03157.x}, author = {Cesaro, Simone and Zanazzo, Andrea Giulio and Frenos, Stefano and Luksch, Roberto and Pegoraro, Anna and Tridello, Gloria and Dallorso, Sandro} } @article {1635, title = {Incidence of bacteremias and invasive mycoses in children with acute non-lymphoblastic leukemia: results from a multi-center Italian study.}, journal = {Pediatr Blood Cancer}, volume = {55}, year = {2010}, month = {2010 Dec 1}, pages = {1103-7}, abstract = {

BACKGROUND: Data on the epidemiology of bacteremias and invasive fungal diseases (IFD) in children with acute myeloid leukemia (AML) are scarce.

DESIGN AND METHODS: In a multi-center, retrospective study, we analyzed proportion, rate per 1,000 person-days at risk, and cumulative risk of bacteremias and IFD in children with AML.

RESULTS: Between January 1998 and December 2005, 240 children were treated for AML at 8 Italian Centers, for a total of 521 treatment courses and 63,232 person-days at risk. Bacteremia was observed in 32\% of treatment courses and IFD was seen in 10\% (P < 0.0001), with rates of 2.62 and 0.84, respectively (P < 0.001). There was a significantly higher frequency of IFD during relapse treatment: proportion 15\% versus 9\% (P = 0.05), rate 2.10 versus 0.64 (P = 0.008) and cumulative risk 32\% versus 12\% (P = 0.007), while there were no differences in the proportion, rate and cumulative risk of bacteremia during front-line or relapse treatment. The epidemiology of bacteremias and IFD was different during front-line therapy for M3 as compared to other types of AML, but the differences were not statistically significant.

CONCLUSIONS: Severe infectious complications are frequent during the treatment of pediatric AML, especially during relapse treatment, and bacteremias are more frequent than IFD.

}, keywords = {Antineoplastic Combined Chemotherapy Protocols, Bacteremia, Child, Female, Follow-Up Studies, Humans, Incidence, Italy, Leukemia, Myeloid, Acute, Male, Mycoses, Neoplasm Recurrence, Local, Retrospective Studies}, issn = {1545-5017}, doi = {10.1002/pbc.22750}, author = {Castagnola, Elio and Rossi, Mario R and Cesaro, Simone and Livadiotti, Susanna and Giacchino, Mareva and Zanazzo, Giulio and Fioredda, Francesca and Beretta, Chiara and Ciocchello, Francesca and Carli, Modesto and Putti, Maria Caterina and Pansini, Valeria and Berger, Massimo and Licciardello, Maria and Farina, Silvia and Caviglia, Ilaria and Haupt, Riccardo} } @article {1636, title = {Morbidity of pandemic H1N1 influenza in children with cancer.}, journal = {Pediatr Blood Cancer}, volume = {55}, year = {2010}, month = {2010 Aug}, pages = {226-8}, abstract = {

BACKGROUND: To define the mortality and the current impact of the H1N1 pandemic in pediatric hematology-oncology centers, we performed a specific survey.

PROCEDURE: Pharyngeal swabs from patients with fevers of unknown origin, flu-like symptoms or bronchopneumonia were screened for H1N1 using PCR.

RESULTS: Sixty-two patients with documented H1N1 infection were reported: 16 had recently stopped therapy, 2 were at the diagnosis stage, and 44 were receiving therapy. The clinical course was severe (requiring ICU admission) in only 1 patient, moderate (requiring hospital admission) in 38, and mild in the remaining 23 (37\%), treated as outpatients. While none of the patients died of H1N1-related complications, two patients died of progressive cancer; in all of the remaining cases, symptoms resolved within 11 days. The clinical course was complicated by respiratory distress or bronchopneumonia in 10 cases. Oseltamivir was given to 82\% of patients. Chemotherapy was temporarily withdrawn in 54\% of cases for a median time of 21 days (range, 4-43 days).

CONCLUSION: H1N1 infection in children with cancer was not reported as the cause of death in any case but resulted in reduced intensity of anti-cancer therapy.

}, keywords = {Adolescent, Antineoplastic Agents, Cause of Death, Child, Child, Preschool, Data Collection, Disease Outbreaks, Humans, Influenza A Virus, H1N1 Subtype, Influenza, Human, Leukemia, Lymphoma, Non-Hodgkin, Morbidity, Neoplasms, Treatment Outcome, Young Adult}, issn = {1545-5017}, doi = {10.1002/pbc.22619}, author = {Caselli, D{\'e}sir{\'e}e and Carraro, Francesca and Castagnola, Elio and Ziino, Ottavio and Frenos, Stefano and Milano, Giuseppe Maria and Livadiotti, Susanna and Cesaro, Simone and Marra, Nicoletta and Zanazzo, Giulio and Meazza, Cristina and Cellini, Monica and Aric{\`o}, Maurizio} } @article {1637, title = {Multidrug resistant Pseudomonas aeruginosa infection in children undergoing chemotherapy and hematopoietic stem cell transplantation.}, journal = {Haematologica}, volume = {95}, year = {2010}, month = {2010 Sep}, pages = {1612-5}, abstract = {

Pseudomonas aeruginosa is one leading gram-negative organism associated with nosocomial infections. Bacteremia is life-threatening in the immunocompromised host. Increasing frequency of multi-drug-resistant (MDRPA) strains is concerning. We started a retrospective survey in the pediatric hematology oncology Italian network. Between 2000 and 2008, 127 patients with Pseudomonas aeruginosa bacteremia were reported from 12 centers; 31.4\% of isolates were MDRPA. Death within 30 days of a positive blood culture occurred in 19.6\% (25/127) of total patients; in patients with MDRPA infection it occurred in 35.8\% (14/39). In the multivariate analysis, only MDRPA had significant association with infection-related death. This is the largest series of Pseudomonas aeruginosa bacteremia cases from pediatric hematology oncology centers. Monitoring local bacterial isolates epidemiology is mandatory and will allow empiric antibiotic therapy to be tailored to reduce fatalities.

}, keywords = {Adolescent, Antineoplastic Agents, Bacteremia, Child, Child, Preschool, Drug Resistance, Multiple, Female, Hematopoietic Stem Cell Transplantation, Humans, Immunocompromised Host, Infant, Infant, Newborn, Italy, Male, Pseudomonas aeruginosa, Pseudomonas Infections, Retrospective Studies, Young Adult}, issn = {1592-8721}, doi = {10.3324/haematol.2009.020867}, author = {Caselli, D{\'e}sir{\'e}e and Cesaro, Simone and Ziino, Ottavio and Zanazzo, Giulio and Manicone, Rosaria and Livadiotti, Susanna and Cellini, Monica and Frenos, Stefano and Milano, Giuseppe M and Cappelli, Barbara and Licciardello, Maria and Beretta, Chiara and Aric{\`o}, Maurizio and Castagnola, Elio} }