Publications by authors named "Katia Perruccio"

65 Publications

A host signature based on TRAIL, IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: A prospective, multicentre cohort study.

Clin Microbiol Infect 2021 Nov 9. Epub 2021 Nov 9.

Pietro Barilla Children's Hospital, Department of Medicine and Surgery, University of Parma, Parma, Italy.

Objectives: Identifying infection aetiology is essential for appropriate antibiotic use. Previous studies showed a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections.

Methods: This prospective, multicentre cohort study titled "AutoPilot-Dx", aimed to validate signature performance and estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data.

Results: In total, 1140 patients were recruited (2/2017-12/2018), of which 1008 met eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with sensitivity of 93.7% (95% CI, 88.7-98.7), specificity of 94.2% (92.2-96.1), positive predictive value of 73.0% (65.0-81.0), negative predictive value of 98.9% (98.0-99.8), and 9.8% equivocal test results. The signature performed consistently across different patient subgroups and detected bacterial immune response in viral PCR positive patients.

Conclusions: The findings validate high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort and support its potential to reduce antibiotic overuse in children with viral infections.

Trial Registration: Clinicaltrials.gov identifier: NCT03052088.
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http://dx.doi.org/10.1016/j.cmi.2021.10.019DOI Listing
November 2021

Efficacy, safety and feasibility of treatment of chronic HCV infection with directly acting agents in hematopoietic stem cell transplant recipients - Study of infectious diseases working party of EBMT.

J Infect 2021 Oct 29. Epub 2021 Oct 29.

Department of Pediatric Hematology and Oncology, University Hospital, Collegium Medicum UMK Torun, Bydgoszcz, Poland.

Objectives: Limited data is available on HCV directly acting agents (DAAs) in haematopoietic stem cell transplant (HSCT) recipients. This study aimed at reporting the characteristics, treatment practices and treatment efficacy in HSCT recipients with chronic HCV.

Methods: Prospective observational study from EBMT Infectious Diseases Working Party (IDWP). Patients with chronic HCV infection were included.

Results: Between 12/2015 and 07/2018, 45 patients were included: male in 53%; median age 49 years (range, 8-75); acute leukaemia in 48.9%, lymphoma in 17.7%, non-malignant disorders in 22.3%; allogeneic HSCT in 84%; 77.8% no immunosuppressive treatment. Genotypes 1, 2, 3 and 4 were detected in 54.5%, 20.5%, 13.6% and 11.4%, respectively; advanced fibrosis in 40%, including cirrhosis in 11.4%. Overall, 37 (82.2%) patients received DAAs, at a median of 8.4 years after HSCT (16.2% within 6 months from HSCT). Sofosbuvir-based treatment was given to 62.2%. Thirty-five patients completed planned treatment course, with sustained virological response (SVR) of 89.1%, and 94.3% (33/35) in those who completed the treatment. Side effects possibly related to DAAs were reported in 5 (14%) and did not require treatment discontinuation.

Conclusions: DAAs treatment was effective, safe and feasible in this cohort of mainly allogeneic HSCT recipients with mild/moderate liver damage.
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http://dx.doi.org/10.1016/j.jinf.2021.10.024DOI Listing
October 2021

Prevention of recurrent respiratory infections : Inter-society Consensus.

Ital J Pediatr 2021 Oct 25;47(1):211. Epub 2021 Oct 25.

Department of Public Health and Infectious Diseases, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.
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http://dx.doi.org/10.1186/s13052-021-01150-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543868PMC
October 2021

Ecthyma Gangrenosum in Children With Cancer: Diagnosis at a Glance: A Retrospective Study From the Infection Working Group of Italian Pediatric Hematology Oncology Association.

Pediatr Infect Dis J 2021 Oct 19. Epub 2021 Oct 19.

From the Pediatric Oncology and Hematology, University Hospital of Policlinico, Bari; Paediatric Oncology and Haematology Unit "Lalla Seràgnoli", Department of Paediatrics, University of Bologna, Sant'Orsola Malpighi Hospital, Bologna; Pediatric Hematology Oncology, IRCCS Policlinico San Matteo, University of Pavia; Terapia Intensiva Neonatale, AOU Policlinico "G. Rodolico-San Marco", Catania; UOS di Oncoematologia Pediatrica, Dipartimento di Ematologia, Medicina Trasfusionale e Biotecnologie, Ospedale Spirito Santo, Pescara; Oncoematologia Pediatrica, Ospedale Meyer, Firenze; Pediatric Hemato-Oncology, Fondazione MBBM, Milano Bicocca University, San Gerardo Hospital, Monza; Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria, Ospedale Santa Maria della Misericordia, Perugia; Clinic of Pediatric Hemato-Oncology, Department of Women's and Children's Health, University Hospital of Padova; Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste; Scuola di Specializzazione in Pediatria, Università degli Studi di Modena e Reggio Emilia; SC di Oncoematologia Pediatrica, AOU Policlinico di Modena; Centro di Riferimento Regionale di Ematologia ed Oncologia Pediatrica, AOU Policlinico "G. Rodolico-San Marco", Catania; Oncoematologia Pediatrica e Patologia della Coagulazione, Ospedale Pediatrico Microcitemico "Antonio Cao", AO Brotzu, Cagliari; UOC Oncoematoogia Pediatrica, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo; and Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Policlinico "G.B: Rossi", Verona, Italy.

Background: To depict ecthyma gangrenosum (EG) clinical presentation and evolution in a large multicenter pediatric retrospective collection of children with malignancies or bone marrow failure syndromes, to facilitate early diagnosis.

Methods: EG episodes diagnosed in the period 2009-2019 were identified by a retrospective review of clinical charts at centers belonging to the Italian Pediatric Hematology Oncology Association.

Results: Thirty-eight cases of EG occurring in children (male/female 16/22; median age 5.2 years) with hematologic malignancy (29), allogeneic stem cell transplantation (2) or relapsed/refractory solid tumor (3) were collected. The involved sites were: perineal region (19), limbs (10), trunk (6), head and the iliac crest (3). Bacteremia was present in 22 patients. Overall, the germs isolated were Pseudomonas aeruginosa (30), Stenotrophomonas maltophilia (3) and Escherichia coli (1); 31% of them were multidrug-resistant. All patients received antibacterial treatment, while surgery was performed in 24 patients (63.1%). Predisposing underlying conditions for EG were severe neutropenia (97.3%), corticosteroid treatment (71%) and iatrogenic diabetes (23.7%). All patients recovered, but EG recurred in 5 patients. Nine patients (24%) showed sequelae (deep scars, with muscle atrophy in 2). Four patients (10.5%) died, 1 due to relapse of EG with Carbapenem-resistant Enterobacteriaceae co-infection and 3 due to the progression of the underlying disease.

Conclusions: EG requires early recognition and a proper and timely treatment to obtain the recovery and to avoid larger necrotic lesions, eventually evolving in scarring sequelae.
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http://dx.doi.org/10.1097/INF.0000000000003377DOI Listing
October 2021

Case Report: Remdesivir and Convalescent Plasma in a Newly Acute B Lymphoblastic Leukemia Diagnosis With Concomitant Sars-CoV-2 Infection.

Front Pediatr 2021 2;9:712603. Epub 2021 Aug 2.

Pediatric Onco-Hematology With Bone Marrow Transplantation Unit, Azienda Ospedaliera di Perugia, Perugia, Italy.

The spread of Covid-19 has worsened the prognosis of oncology patients, interrupting or delaying life-saving therapies and contextually increasing the risk of severe SARS-CoV-2 infections. Acute lymphoblastic leukemia (ALL) is the most frequent cancer in pediatric age and the management of this disease with concomitant SARS-COV-2 infection represents a challenging situation. We present the case of a 6-year-old female newly diagnosed with ALL during a documented SARS-CoV-2 infection. Our patient was admitted 20 days after SARS-CoV-2 detection for evening-rise fever. Laboratory testing showed severe neutropenia while chest x-ray detected moderate pulmonary involvement. Acute lymphoblastic leukemia diagnosis was made through morphological and molecular analysis on bone marrow aspirate. Given the stability of the blood count and clinical conditions, antiviral therapy with Remdesivir and Convalescent Plasma was started before antileukemic treatment, obtaining a rapid resolution of the infection. In our experience, the treatment with Remdesivir and Convalescent Plasma led to a rapid resolution of Sars-Cov-2 infection. Our case did not present any adverse event to the therapy. Thus, this treatment could be considered in patients with malignancies, in order to accelerate the resolution of the infection and begin immunosuppressive treatment safely. Further studies are required to confirm this hypothesis.
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http://dx.doi.org/10.3389/fped.2021.712603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365506PMC
August 2021

Effect of EPA on Neonatal Pig Sertoli Cells "": A Possible Treatment to Help Maintain Fertility in Pre-Pubertal Boys Undergoing Treatment With Gonado-Toxic Therapies.

Front Endocrinol (Lausanne) 2021 20;12:694796. Epub 2021 May 20.

Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

The incidence of cancer in pre-pubertal boys has significantly increased and, it has been recognized that the gonado-toxic effect of the cancer treatments may lead to infertility. Here, we have evaluated the effects on porcine neonatal Sertoli cells (SCs) of three commonly used chemotherapy drugs; cisplatin, 4-Hydroperoxycyclophosphamide and doxorubicin. All three drugs induced a statistical reduction of 5-hydroxymethylcytosine in comparison with the control group, performed by Immunofluorescence Analysis. The gene and protein expression levels of GDNF, were significantly down-regulated after treatment to all three chemotherapy drugs comparison with the control group. Specifically, differences in the mRNA levels of GDNF were: 0,8200 ± 0,0440, 0,6400 ± 0,0140, 0,4400 ± 0,0130 fold change at 0.33, 1.66, and 3.33μM cisplatin concentrations, respectively (**p < 0.01 at 0.33 and 1.66 μM SCs and ***p < 0.001 at 3.33μM SCs); 0,6000 ± 0,0340, 0,4200 ± 0,0130 fold change at 50 and 100 μM of 4-Hydroperoxycyclophosphamide concentrations, respectively (**p < 0.01 at both these concentrations SCs); 0,7000 ± 0,0340, 0,6200 ± 0,0240, 0,4000 ± 0,0230 fold change at 0.1, 0.2 and 1 µM doxorubicin concentrations, respectively (**p < 0.01 at 0.1 and 0.2 μM SCs and ***p < 0.001 at 1 μM SCs). Differences in the protein expression levels of GDNF were: 0,7400 ± 0,0340, 0,2000 ± 0,0240, 0,0400 ± 0,0230 A.U. at 0.33, 1.66, and 3.33μM cisplatin concentrations, respectively (**p < 0.01 at both these concentrations SCs); 0,7300 ± 0,0340, 0,4000 ± 0,0130 A.U. at 50 and 100 μM of 4- Hydroperoxycyclophosphamide concentrations, respectively (**p < 0.01 at both these concentrations SCs); 0,6200 ± 0,0340, 0,4000 ± 0,0240, 0,3800 ± 0,0230 A.U. at 0.l, 0.2 and 1 µM doxorubicin concentrations, respectively (**p < 0.01 at 0.1 and 0.2 μM SCs and ***p < 0.001 at 1 μM SCs). Furthermore, we have demonstrated the protective effect of eicosapentaenoic acid on SCs only at the highest concentration of cisplatin, resulting in an increase in both gene and protein expression levels of GDNF (1,3400 ± 0,0280 fold change; **p < 0.01 SCs); and of AMH and inhibin B that were significantly recovered with values comparable to the control group. Results from this study, offers the opportunity to develop future therapeutic strategies for male fertility management, especially in pre-pubertal boys.
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http://dx.doi.org/10.3389/fendo.2021.694796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174840PMC
May 2021

A multicentre, multinational, prospective, observational registry study of defibrotide in patients diagnosed with veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic cell transplantation: an EBMT study.

Bone Marrow Transplant 2021 10 31;56(10):2454-2463. Epub 2021 May 31.

Department of Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Severe hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT). This multinational, prospective, observational study (NCT03032016), performed by the EBMT, enrolled patients treated with defibrotide from April 2015 to July 2018. This analysis focused on defibrotide-treated patients with VOD/SOS post-HCT. The primary endpoint was incidence of serious adverse events (SAEs) of interest up to 12 months post-HCT in patients with severe VOD/SOS. Overall, 104 defibrotide-treated patients with VOD/SOS post-HCT were enrolled: 62 had severe VOD/SOS and comprised the primary study population, including 36 with multi-organ dysfunction/failure (MOD/MOF). SAEs of interest occurred in 20 of 62 (32%) severe VOD/SOS patients; the most common by category were infection (24%) and bleeding (13%). In patients with severe VOD/SOS, the Kaplan-Meier-estimated Day 100 survival rate was 73% (95% CI: 60%, 82%) with VOD/SOS resolution by Day 100 in 45 of 62 (73%) patients. MOD/MOF resolved in 19 of 36 (53%) patients with MOD/MOF at VOD/SOS diagnosis. Results from this multicentre registry study build on prior defibrotide studies supporting the utility of defibrotide for the treatment of VOD/SOS post-HCT. These results provide additional real-world evidence of the effectiveness and safety of defibrotide in patients with VOD/SOS post-HCT.
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http://dx.doi.org/10.1038/s41409-021-01265-2DOI Listing
October 2021

Prophylaxis With Trimethoprim/Sulfamethoxazole Is Not Necessary in Children With Solid Tumors Treated With Low-medium Intensity Chemotherapy.

Pediatr Infect Dis J 2021 04;40(4):354-355

Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Prophylaxis of Pneumocystis jiroveci pneumonia (PJP) with trimethoprim/sulfamethoxazole is a standard of care for children with hematologic malignancies, while its use in solid tumor patients is still debated. A retrospective study focusing on the use of PJP prophylaxis in patients with solid tumors was performed among 16 AIEOP centers: 1046/2863 patients did not receive prophylaxis and no cases of PJP were reported.
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http://dx.doi.org/10.1097/INF.0000000000003044DOI Listing
April 2021

Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality.

J Infect 2020 12 10;81(6):882-894. Epub 2020 Nov 10.

ICO-Hospital Universitari Germans Trias I Pujol, Badalona, Spain. Electronic address:

Objectives: We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality.

Methods: Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center` fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT).

Results: The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-allo-HSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location not in northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence.

Conclusions: Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality.
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http://dx.doi.org/10.1016/j.jinf.2020.11.002DOI Listing
December 2020

Impact of invasive aspergillosis occurring during first induction therapy on outcome of acute myeloid leukaemia (SEIFEM-12B study).

Mycoses 2020 Oct 23;63(10):1094-1100. Epub 2020 Aug 23.

Istituto di Ematologia, Fondazione Policlinico Universitario A. Gemelli-IRCCS-Università Cattolica del Sacro Cuore, Roma, Italy.

Background: Acute myeloid leukaemia (AML) patients are at high risk of invasive aspergillosis (IA) after first induction chemotherapy (CHT). Although IA risk factors have been identified, few data are available on impact of IA, occurring during induction phase, on overall AML outcome.

Patients And Results: The end point of this multicentre, case-control, study was to evaluate whether IA, occurring after first induction CHT, can affect treatment schedule and patient's outcome. We identified 40 AML patients (cases) who developed IA during first induction phase, 31 probable (77.5%) and 9 proven (22.5%). These cases were matched with a control group (80 AML) without IA, balanced according to age, type of CHT, AML characteristics and cytogenetic-molecular risk factors. The overall response rate to induction CHT was the same in the 2 groups. In the 40 cases with IA, the overall response rate to antifungal treatment was favourable (80%) but it was significantly affected by the achievement of leukaemia complete remission (CR) with induction CHT. In fact, in cases with AML responsive to induction CHT, responses of IA to antifungal therapy were 96% compared to 21% in cases of AML not responsive to induction treatment (P < .0001). The adherence to the schedule and full doses of CHT were reported in 35% of cases (14/40) and in 76% of controls (61/80) (P = .0001; OR 6.7; 95% CI 2.7-16.6). After first induction CHT, a significant higher number of cases (15/40; 37.5%) compared to controls (9/80; 11%) could not receive additional cycles of CHT (P = .0011, OR 4.8; 95% CI 1.9-12.3). The IA-related mortality was 22.5%. The median OS of cases was significantly worse than OS of controls with a difference of 12.3 months (12.1 vs 24.4 months, P = .04). However, the occurrence of IA during first induction phase did not have a significant impact on the OS of cases who achieved a CR of AML with induction CHT which are able to proceed, despite the IA, with their therapeutic program, achieving the same OS as the control group with AML in CR (P = ns).

Conclusions: These data show that IA during first induction CHT can delay the subsequent therapeutic program and has a significant impact on OS, specifically in AML patients who did not achieved a CR of AML with the first course of CHT.
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http://dx.doi.org/10.1111/myc.13147DOI Listing
October 2020

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.

Cancers (Basel) 2020 Jun 18;12(6). Epub 2020 Jun 18.

Pediatric Hematology Oncology Unit, Azienda Ospedaliero Universitaria of Parma, 43126 Parma, Italy.

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.
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http://dx.doi.org/10.3390/cancers12061620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352443PMC
June 2020

Posaconazole delayed-release tablets in paediatric haematology-oncology patients.

Mycoses 2020 Jun 15;63(6):604-609. Epub 2020 Apr 15.

Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

Background: To date, there are few studies that describe pharmacokinetics, safety and efficacy of posaconazole delayed-release tablet (DRT) formulation in the paediatric population.

Objectives: We evaluated retrospectively posaconazole plasma concentrations and safety of posaconazole DRT in paediatric haematology-oncology patients.

Patients And Methods: Posaconazole DRT was assessed in 28 haematological paediatric patients with a median age 15 of years (range 5-18) and a median body weight of 50 kg (range 22-83 kg). Twenty-one patients received posaconazole DRT as prophylaxis and 7 patients as therapy.

Results: As prophylaxis, the median daily dose was 5.5 mg/kg/day (range 2.2-22.2) with posaconazole trough level ≥ 0.7 μg/mL in 80% by first week, 62.5% by second week and 87.5% by fourth week. As therapy, the median daily dose was 4 mg/kg/day (range 3.3-4.5) with trough level ≥ 1 μg/mL 100% by first week, 80% by second week and 33.4% by fourth week.

Conclusions: Posaconazole DRT is feasible in paediatric patients capable to swallow tablets. Specific pharmacokinetic studies are needed.
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http://dx.doi.org/10.1111/myc.13084DOI Listing
June 2020

Chemotherapy-Related Encephalopathy With Super-Refractory Status Epilepticus in a Child With Osteosarcoma: A Case Report With a Review of Literature.

Front Pharmacol 2019 2;10:963. Epub 2019 Sep 2.

Pediatric Oncohematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.

Osteosarcoma is the most frequent primary cancer of the bones, and a combination of primary chemotherapy, surgery, and adjuvant chemotherapy is its current treatment. In adults, some authors have reported problems with memory and concentration following chemotherapy, but in children, severe neurologic dysfunction has been rarely reported. This report describes a 13-year-old patient with primary high-grade nonmetastatic osteosarcoma of the tibia who developed encephalopathy with super-refractory status epilepticus related to chemotherapy. He received methotrexate (MTX) and cisplatin (CDDP)-containing polychemotherapy, and after the first course of drug administration, he developed fever, confusion, a state of psychomotor agitation, and super-refractory status epilepticus with normal laboratory and imaging findings. The causal relationship between the administration of the first polychemotherapy course and his neurological manifestations may be supported by the evaluation and exclusion of other causes. The administration of antiepileptic drugs and off-label atypical antipsychotics was necessary to treat his neurological complications and behavioral changes. This patient represents the first known example of super-refractory status epilepticus in a child treated with MTX and CDDP-containing chemotherapy. Physicians should be aware that encephalopathy and seizures are possible consequences of CDDP therapy when administered alone or in combination with other chemotherapeutic agents. Further studies are needed to better define this relationship in children.
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http://dx.doi.org/10.3389/fphar.2019.00963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734028PMC
September 2019

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors: A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (GITMO).

Biol Blood Marrow Transplant 2019 12 7;25(12):2388-2397. Epub 2019 Aug 7.

Centro Unico Regionale Trapianto Cellule Staminali e Terapie Cellulari A. Neri, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.

We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatment A total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016). Of these 441 patients, 404 (92%) were in cytologic complete remission (CR), whereas the remaining 37 (8%) had active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of patients. The most prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (total body irradiation-based in 50%) and included antithymocyte globulin in 51% of patients. With a median follow-up after HSCT of 39.4 months (range, 1 to 145 months), the probability of overall survival (OS) at 1, 2, and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2, and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients who were in CR and MRD-negative at the time of HSCT compared with patients who were in CR but MRD-positive (50% OS not reached versus 36 months; P = .015; 50% PFS not reached versus 26 months, P = .003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5-year OS, 70%). Conversely, the 37 patients who underwent a HSCT with active Ph ALL had a median OS of 7 months and a median PFS of 5 months. The 5-year cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% versus 35.4%; P = .001). Nonrelapse mortality (NRM) after 1, 2, and 5 years was 19.1% (95% confidence interval [CI], 15.5% to 22.9%), 20.7% (95% CI, 17% to 24.7%), and 24.1% (95% CI, 20% to 28.5%), respectively. NRM was significantly lower with a modified European Society for Blood and Marrow Transplantation (mEBMT) risk score of 0 to 2 compared with ≥3 (15% versus 25%; P = .016). The median OS for Ph ALL patients who underwent a TKI-based treatment followed by an allogeneic HSCT, in recent years at the GITMO centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph ALL with an excellent outcome for the subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT (5-year OS, 70%).
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http://dx.doi.org/10.1016/j.bbmt.2019.07.037DOI Listing
December 2019

A bronchoalveolar lavage-driven antimicrobial treatment improves survival in hematologic malignancy patients with detected lung infiltrates: A prospective multicenter study of the SEIFEM group.

Am J Hematol 2019 10 9;94(10):1104-1112. Epub 2019 Aug 9.

Fondazione Policlinico Universitario Agostino Gemelli - IRCCS, Rome, Italy.

Bronchoalveolar lavage (BAL) is recommended for diagnosing lung infiltrates (LI) in patients with hematologic malignancy (HM). Prospective data on the impact of BAL on survival are still lacking. We conducted a prospective observational study on patients who performed BAL for LI among 3055 HM patients hospitalized from January to September 2018. The BAL was performed in 145 out of 434 patients who developed LI, at a median time of four days from LI detection. The median age was 60 (1-83). Most patients had an acute myeloid leukemia/myelodisplastic syndrome (81), followed by lymphoma (41), acute lymphoblastic leukemia (27), and other types of HM (36). A putative causal agent was detected in 111 cases (76%), and in 89 cases (61%) the BAL results provided guidance to antimicrobial treatment. We observed a significantly improved outcome of LI at day +30 in patients who could receive a BAL-driven antimicrobial treatment (improvement/resolution rate: 71% vs 55%; P = .04). Moreover, we observed a significantly improved outcome in 120-day overall survival (120d-OS) (78% vs 59%; P = .009) and 120-day attributable mortality (120d-AM) (11% vs 30%; P = 0.003) for patients who could receive a BAL-driven treatment. The multivariate analysis showed that BAL-driven antimicrobial treatment was significantly associated with better 120d-OS and lower 120d-AM. We did not observe any severe adverse events. In conclusion BAL allows detection of a putative agent of LI in about 75% of cases, it is feasible and well tolerated in most cases, demonstrating that a BAL-driven antimicrobial treatment allows improvement of clinical outcome and survival.
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http://dx.doi.org/10.1002/ajh.25585DOI Listing
October 2019

Invasive mucormycosis in children with cancer: A retrospective study from the Infection Working Group of Italian Pediatric Hematology Oncology Association.

Mycoses 2019 Feb 13;62(2):165-170. Epub 2018 Nov 13.

Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Background: Invasive mucormycosis is a rare but frequently fatal fungal disease. The acute and rapidly progressive evolution causes unfavourable outcome in 22%-59% of patients and its treatment represents a clinical challenge, especially in immunocompromised patients. Current data in paediatric oncological patients are limited.

Objectives: The infection Working Group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) analysed the episodes of invasive mucormycosis occurred between 2009 and 2016.

Patients: Fifteen cases of proven mucormycosis (male/female 8/7; median age 14.1 years, range 7.7-18.6) were reported after chemotherapy for acute leukaemia and lymphoma (12) and allogeneic stem cell transplantation (3). The aetiology was Rhizopus oryzae 4, Lichtheimia corymbifera 3 and Mucor spp. 8.

Results: Paranasal sinus was the primary site of infection in 14/15 patients combined with orbital involvement (9), central nervous system (8), lung (4), thyroid gland and kidney (1). All patients received liposomal Amphotericin B (L-AmB) (3-10 mg/kg), with surgical debridement in 14/15 cases. Eleven patients received maintenance treatment with posaconazole (9) or isavuconazole (2). Eight out of fifteen patients (53.3%) died, after 3-6 months.

Conclusions: Mucormycosis involved mainly the sinu-orbital site and affected children >10 years. Despite aggressive treatment with high-dose L-AmB and timely surgical debridement, the mortality rate remains still high.
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http://dx.doi.org/10.1111/myc.12862DOI Listing
February 2019

High Incidence of Early Human Herpesvirus-6 Infection in Children Undergoing Haploidentical Manipulated Stem Cell Transplantation for Hematologic Malignancies.

Biol Blood Marrow Transplant 2018 12 29;24(12):2549-2557. Epub 2018 Jul 29.

Pediatric Hematology-Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Human herpesvirus-6 (HHV-6) infection is increasingly recognized among allogeneic hematopoietic stem cell transplantation (HSCT) recipients, with 30% at risk of reactivation in the haploidentical setting. It has been associated with encephalitis, acute graft-versus-host disease, and graft failure. Here we report 2 cohorts of pediatric haploidentical manipulated HSCT in which, despite many differences, HHV-6 reactivation and disease occurred with very high incidence compared with data reported in the literature and represented the main early post-transplant infectious complication compared with other viral, bacterial, or fungal infections. The 2 cohorts were recruited at the pediatric transplant centers of Perugia (n = 13), Barcelona (n = 10), and Madrid (n = 15). All patients received myeloablative conditioning regimens and 2 different types of ex vivo graft manipulation: CD34 selection and regulatory T cell/conventional T cell infusion in 13 patients and CD45RA T cell depletion in 25 patients. Antiviral prophylaxis was acyclovir in 33 and foscarnet in 5 patients. HHV-6 DNAemia was checked by quantitative or qualitative PCR. In vitro experiments demonstrated that donor CD4 T cells are the reservoir of HHV-6 and suggested a role of the graft composition in both transplant settings (rich in CD4 T cells) in the high rate of HHV-6 infections. All patients presented very early HHV-6 DNAemia after transplantation, and although viremic, 9 patients (24%) developed symptomatic limbic encephalitis. All patients responded to antiviral treatment, and none died of infection, although 2 experienced long-term neurologic sequelae (22%). Moreover, 6 patients presented organ involvement in absence of other causes: 1 hepatitis, 1 pneumonia, 2 gastroenteritis, and 2 multiorgan involvement(1 encephalitis, pneumonia, and gastritis; 1 pneumonia and enteritis). Incidences of other viral, bacterial, and fungal diseases were lower in both cohorts. In vitro, HHV-6 was found to infect only CD4 fraction of the graft. Co-culturing CD4 T cells with CD56 natural killer (NK) cells eliminated the virus, demonstrating the main role of NK cells in the antiviral immune response. All 38 pediatric patients undergoing these manipulated haploidentical HSCTs showed HHV-6 reactivation, and 14 of 38 developed HHV-6 disease with similar features in terms of timing, morbidity, response to treatment, and outcome. The graft composition in both transplant platforms, rich in CD4 T cells and poor in NK cells, seems to play a key role. HHV-6 DNAemia surveillance was useful to diagnose and treat preemptively HHV-6 infection.
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http://dx.doi.org/10.1016/j.bbmt.2018.07.033DOI Listing
December 2018

Posaconazole oral dose and plasma levels in pediatric hematology-oncology patients.

Eur J Haematol 2018 Mar 10;100(3):315-322. Epub 2018 Jan 10.

Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Background: Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole oral solution daily dosage/kg/body weight and trough plasma level.

Methods: A total of 97 hematology-oncology pediatric patients with ≥1 posaconazole plasma concentration level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included.

Results: Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%). The median daily dose/kg/bw ranged from 10 to 12 mg in the prophylaxis group and 12.5 to 16.5 mg in the therapy group. The median value of PPC for the prophylaxis group was 0.9 and 0.8 μg/mL at the first and second/third determinations, respectively. Posaconazole prophylaxis failed in 4 of 84 patients (5%). The median value of PPC for the therapy group was 1.5 and 1.4 μg/mL at the first/second and the third determination, respectively. Posaconazole-related side effects were reported in 6 patients and all regressed with the suspension of the drug. In the prophylaxis group, the use of proton-pump inhibitors was significantly associated with a lower PPC, P = 0.04.

Conclusions: Posaconazole may be a valuable antifungal agent in children despite the incomplete knowledge of its pharmacokinetic characteristics.
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http://dx.doi.org/10.1111/ejh.13017DOI Listing
March 2018

Biliary tract rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Associazione Italiana Ematologia Oncologia Pediatrica.

Tumori 2018 Jun 8;104(3):232-237. Epub 2018 May 8.

13 Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan - Italy.

Introduction: Rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor frequent in children. Biliary duct localization is extremely rare, but it is the most common cause of malignant obstructive jaundice in pediatric patients.

Methods: This report describes a series of 10 patients under 18 years of age with biliary tract rhabdomyosarcoma who were enrolled, from 1979 to 2004, in 3 consecutive Italian pediatric cooperative protocols that had been drawn up by the Soft Tissue Sarcoma Committee of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

Results: Considering initial and delayed surgery, tumor resection was achieved in 7 cases, 3 complete with free margins (2 liver transplants) and 4 with microscopic residual disease. Chemotherapy was given to all patients and radiotherapy to 3. At present, 5 patients survive in complete remission 90-200 months after diagnosis while 4 died of disease progression or relapse and 1 of liver transplant-related complications.

Conclusions: Better outcomes in this series were associated with the feasibility of conservative surgery due to the favorable location of the tumor, in particular in the common bile duct. Chemotherapy and radiotherapy might obviate the need for demolitive surgery or liver transplant, which were linked to worse outcomes in our series.
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http://dx.doi.org/10.5301/tj.5000692DOI Listing
June 2018

Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey.

Clin Infect Dis 2017 Nov;65(11):1884-1896

Dipartimento di Medicina Sperimentale e Clinica, University of Florence.

Background: Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable.

Methods: We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant.

Results: The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P = .01).

Conclusions: Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB.

Clinical Trials Registration: NCT02088840.
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http://dx.doi.org/10.1093/cid/cix690DOI Listing
November 2017

Retrospective study on the incidence and outcome of proven and probable invasive fungal infections in high-risk pediatric onco-hematological patients.

Eur J Haematol 2017 Sep 30;99(3):240-248. Epub 2017 Jun 30.

Pediatric Hematology Oncology, Meyer Hospital, University of Florence, Firenze, Italy.

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.
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http://dx.doi.org/10.1111/ejh.12910DOI Listing
September 2017

Abdomen/pelvis computed tomography in staging of pediatric Hodgkin Lymphoma: is it always necessary?

Cancer Med 2016 09 3;5(9):2359-67. Epub 2016 Aug 3.

Radiology Unit, Radiology Department, A.R.N.A.S. Ospedali Civico, Di Cristina e Benfratelli, Palermo, Italy.

The purpose of the study was to determine if abdomen/pelvis computed tomography (CT) can be safety omitted in the initial staging of a subgroup of children affected by Hodgkin Lymphoma (HL). Every participating center of A.I.E.O.P (Associazione Italiana di Ematologia ed Oncologia Pediatrica) sent local staging reports of 18F-fluorodeoxyglucose positron emission tomography (PET) and abdominal ultrasound (US) along with digital images of staging abdomen/pelvis CT to the investigation center where the CT scans were evaluated by an experienced pediatric radiologist. The local radiologist who performed the US was unaware of local CT and PET reports (both carried out after US), and the reviewer radiologist examining the CT images was unaware of local US, PET and CT reports. A new abdominal staging of 123 patients performed on the basis of local US report, local PET report, and centralized CT report was then compared to a simpler staging based on local US and PET. No additional lesion was discovered by CT in patients with abdomen/pelvis negativity in both US and PET or isolated spleen positivity in US (or US and PET), and so it seems that in the initial staging, abdomen/pelvis CT can be safety omitted in about 1/2 to 2/3 of children diagnosed with HL.
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http://dx.doi.org/10.1002/cam4.829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055149PMC
September 2016

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

Pediatr Blood Cancer 2015 Oct 22;62(10):1782-9. Epub 2015 May 22.

Department of Women's and Children's Health, Clinic of Pediatric Hemato-Oncology, University of Padova, Italy.

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 (2.4%) had an associated inherited condition and a mature B-lineage (n = 28), anaplastic large cell lymphoma (n = 4), or T-lineage (n = 2) NHL. Their median age at the diagnosis was 9.3 years (range, 2.6-17.8 years). In 14 cases (41%) the underlying condition was considered to be a potential cause for undue toxicity if the expected therapy was applied. Thus, treatment modification had been planned in advance. The overall survival was 89% (standard error [SE] 1%), 73% (SE 10%), and 73% (SE 23%) at 3 years for registered patients with no inherited condition associated, with genetic abnormalities and with underlying condition causing an immune deficiency, respectively (P = 0.003).

Conclusion: In our cohort, patients with NHL with an underlying constitutional condition represent the 2.4% of the cases. In the subset of patients with primary immune deficiency, which may have contributed to lymphomagenesis, allogeneic hematopoietic stem cell transplantation may be required. In the remaining patients, the association with lymphoma remains apparently unexplained and could be not causative. Detailed reporting of such cases may contribute to disclose even rare and fully unexpected association, which may have implications for research in the field of lymphomagenesis.
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http://dx.doi.org/10.1002/pbc.25565DOI Listing
October 2015

Differences in Aspergillus-specific immune recovery between T-cell-replete and T-cell-depleted hematopoietic transplants.

Eur J Haematol 2015 Dec 16;95(6):551-7. Epub 2015 Mar 16.

Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.

Background: After hematopoietic stem cell transplantation, invasive aspergillosis remains one of the most lethal infections. Susceptibility may be due to prophylaxis and treatment of graft-vs.-host disease in T-cell-replete transplants, and delayed immune rebuilding due to T-cell depletion in haploidentical transplantation.

Methods: We monitored CD4(+) T-cell recovery and anti-Aspergillus immune competence in pediatric recipients of T-cell-replete matched transplants and of prevalently adult recipients of T-cell-depleted matched or haploidentical transplants for hematological malignancies.

Results: Although CD4(+) T-cell counts were higher in T-cell-replete transplant recipients at all post-transplant time points, Aspergillus-specific T cells were first detected 15-18 months after T-cell-replete matched, 7-9 months after T-cell-depleted matched, and 9-12 months after haploidentical transplantation, respectively. Incidence of invasive aspergillosis was 22% with 10% mortality after T-cell-replete transplants, 0% after T-cell-depleted matched, and 7% with 4% mortality after haploidentical transplants.

Conclusions: Although T-cell counts were significantly higher after T-cell-replete transplants, post-transplant immune suppression/GvHD appeared to impair their function. Specific Aspergillus immune competence recovered faster after T-cell-depleted transplants, whether matched or haploidentical. T-cell-replete transplants were associated with a higher incidence of invasive aspergillosis and Aspergillus-related deaths. These results showed that T-cell depletion without post-transplant immunosuppression is associated to a faster immune recovery than T-cell-replete transplantation.
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http://dx.doi.org/10.1111/ejh.12531DOI Listing
December 2015

Sirolimus-based immunosuppression as GVHD prophylaxis after bone marrow transplantation for severe aplastic anaemia: a case report and review of the literature.

Case Rep Hematol 2015 5;2015:321602. Epub 2015 Jan 5.

Pediatric Oncology Hematology Unit, Perugia General Hospital, Località Sant'Andrea delle Fratte, 06156 Perugia, Italy.

Congenital or acquired severe aplastic anaemia (SAA) is cured by bone marrow transplantation (BMT) from a histocompatible leukocyte antigen- (HLA-) identical sibling. The best conditioning regimen is cyclophosphamide (CTX) with or without antithymocyte globulin (ATG), followed by short-term methotrexate (MTX) and cyclosporine A (CsA) to prevent graft-versus-host disease (GvHD). In our pediatric oncology-hematology unit, a 5-year-old girl with SAA was treated with two BMT from the same HLA-identical sibling donor. Severe CsA-induced adverse events (severe hypertension and PRES) after the first BMT led necessarily to CSA withdrawal. Alternative immunosuppressive treatment for GvHD prevention as tacrolimus and mycophenolate were not tolerated by our patient because toxicity > grade II. For this reason we decided to administrate sirolimus alone as GvHD prophylaxis and to prevent disease relapse after the rescue BMT. Here we report the successful use of sirolimus alone for GvHD prophylaxis after the second transplant in a pediatric BMT setting for SAA.
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http://dx.doi.org/10.1155/2015/321602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299786PMC
January 2015

Management and follow-up of urothelial neoplasms of the bladder in children: a report from the TREP project.

Pediatr Blood Cancer 2015 Jun 24;62(6):1000-3. Epub 2014 Dec 24.

Department of Women's and Children's Health, Hematology/Oncology Division, Padova University Hospital, Padova, Italy.

Background: Urothelial neoplasms of the bladder (UNB) are rare in patients under 20 years of age, and even rarer in the first decade of life. The present series was investigated to provide recommendations on patient management in terms of therapeutic strategy and follow-up.

Procedure: This is a retrospective analysis on 12 patients with UNB under 18 years of age. Data were extracted from the national database of the TREP (Tumori Rari in Età Pediatrica) Project.

Results: Ten of the 12 patients presented with a single episode of hematuria, while the discovery of the lesion was incidental in two. Eleven of the 12 lesions were G1 and one was G2/G3; none of the lesions invaded the lamina propria. All lesions were removed completely by transurethral resection. No further treatment was administered in nine children but three received a single dose of intravesical chemotherapy (epirubicin in 2, mitomycin in 1). Only one patient experienced a recurrence and all patients are alive in complete remission with a median follow-up of 30 months (range 4-112). Follow-up investigations varied at the different centers and included abdominal ultrasound in nine patients, cystoscopy in seven, and additional radiological investigations in a few cases.

Conclusions: UNB in children seems to be a low-grade, scarcely aggressive disease with an excellent prognosis. The role of intravesical chemotherapy is debatable. Follow-up can be based on ultrasound. The adoption of shared recommendations should enable unnecessary treatment and invasive investigations to be avoided.
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http://dx.doi.org/10.1002/pbc.25380DOI Listing
June 2015

Multiple EWSR1-WT1 and WT1-EWSR1 copies in two cases of desmoplastic round cell tumor.

Cancer Genet 2013 Nov 4;206(11):387-92. Epub 2013 Nov 4.

Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy. Electronic address:

To provide new insights into the genomic profile of desmoplastic round cell tumors (DSRCT), we applied fluorescence in situ hybridization (FISH) and metaphase comparative genomic hybridization (M-CGH) to two newly diagnosed cases. FISH detected multiple subclones bearing one to three copies of der(11)t(11;22)(p13;q12) and/or der(22)t(11;22)(p13;q12) in both patients. This peculiar genomic imbalance might result from derivative chromosome duplication due to non-disjunction and/or mitotic recombination between normal and derivative chromosomes 11 and 22. Concomitant loss of normal chromosomes (i.e., 11 in patient 1 and 22 in patient 2) caused loss of the WT1 or EWSR1 wild-type allele. M-CGH identified other genomic imbalances: gain at chromosome 3 in both cases and chromosome 5 polysomy in patient 1. Common genomic events (i.e., trisomy 3 and extra EWSR1-WT1 and WT1-EWSR1 copies) probably contributed to disease pathogenesis and/or evolution of DSRCT. Our study demonstrated that an integrated molecular cytogenetic approach identified EWSR1-WT1 cooperating molecular events and genetic markers for prognosis. Thus, FISH and M-CGH might well be applied in a large series of patients to elucidate the genomic background of DSRCT.
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http://dx.doi.org/10.1016/j.cancergen.2013.10.005DOI Listing
November 2013
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