Katia Perruccio

• MD, PhD
• Medical Doctor at Azienda Ospedaliera di Perugia

Acute lymphoblastic leukemia is the most common childhood malignancy. Despite many advances in therapy, about 15%–20% of children with acute lymphoblastic leukemia experience a disease relapse. Isolated ocular relapse is relatively rare. A 14-year-old male with T-cell acute lymphoblastic leukemia in remission presented with sudden onset of right ey...

Background: Immunotherapy with chimeric antigen receptor (CAR)-expressing T cells that target the disialoganglioside GD2 expressed on tumor cells may be a therapeutic option for patients with high-risk neuroblastoma. Methods: In an academic, phase 1-2 clinical trial, we enrolled patients (1 to 25 years of age) with relapsed or refractory, high-r...

Allogeneic hematopoietic stem cell transplantation (HSCT) is still needed for many children with very high-risk acute leukemia. An HLA-haploidentical family donor is a suitable option for those without an HLA-matched donor. Here we present outcomes of a novel HLA-haploidentical HSCT (haplo-HSCT) strategy with adoptive immunotherapy with thymic-deri...

Unlabelled: Music therapy (MT) is a complementary therapy offered to children, young adults, and their families in pediatric oncology and palliative care. We performed a survey to collect information about MT in pediatric oncology in Italy. The outbreak of COVID-19 unavoidably changed the scenario of MT, suggesting some considerations presented in...

Background: Music therapy (MT) is a complementary therapy offered to children, young adults and their families in pediatric oncology and palliative care. We performed a survey to collect information about MT in pediatric oncology in Italy. The outbreak of COVID-19 unavoidably changed the scenario of MT, suggesting some considerations presented in t...

Background: To investigate the association of viral load (VL) with (i) tumor necrosis factor-related apoptosis inducing ligand (TRAIL), interferon-gamma induced protein-10, C-reactive protein and a combinatorial score (BV score); and (ii) clinical severity. Study design: In this prospective, multicentre cohort sub-study, children with respirator...

Induction chemotherapy is the first-line treatment for pediatric patients with hematologic malignancies. However, several complications may arise, mainly infections and febrile neutropenia, with a strong impact on patient morbidity and mortality. Such complications have been shown to be closely related to alterations of the gut microbiome (GM), mak...

COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 202...

In children affected by malignancies and/or who received hematopoietic stem cell transplantation (HSCT), acute kidney injury (AKI) may occur causing a high mortality rate, despite the implementation of renal replacement therapy (RRT). We performed a nationwide, multicenter, retrospective, observational cohort study including consecutive patients be...

Background: Brentuximab vedotin (BV) is an antibody drug-conjugated anti-CD30 approved for the treatment of adult classical Hodgkin's lymphoma (HL), whereas it is considered as off-label indication in paediatrics. The aim of the study was to evaluate the safety and efficacy of BV to treat patients aged less than 18 years with refractory/relapsed H...

Purpose. To describe ecthyma gangrenosum (EG) characteristics and complications in a large multicenter pediatric retrospective collection of children with malignancies or bone marrow failure syndromes. Methods. EG episodes diagnosed in the period 2009-2019 were identified by a retrospective review of clinical charts at centers belonging to the Ital...

Vaccines represent the best tool to prevent the severity course and fatal consequences of the pandemic by the new Coronavirus 2019 infection (SARS-CoV-2). Considering the limited data on vaccination of pediatric oncohematological patients, we developed a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers i...

Vaccines represent the best tool to prevent the severity course and fatal consequences of pandemic by new Coronavirus 2019 infection (SARS CoV 2). Considering the limited data on vaccination of pediatric oncohematological patients, we develop a Consensus document to support the Italian pediatric hematological oncological (AIEOP) centers in a scient...

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 pro...

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 ye...

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 ch...

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...

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 Part...

Introduction: 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 infe...

Pediatric ependymoma (EPN) is the third most common central nervous system (CNS) tumor, with 90% arising intracranially. Management typically involves maximal surgical resection and radiotherapy, but patients’ outcome is poor. Moreover, there are only a few therapeutical options available for recurrent or refractory disease. In this report, we pres...

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 p...

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 dat...

Background Acute myeloid leukemia (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 endpoint of this multicentre, case‐contr...

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, 175...

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 met...

Objectives We analyzed Isavuconazole use as invasive fungal disease (IFD) treatment or prophylaxis in hemato-oncologic children. Methods M ulticentric retrospective analysis performed among centers belonging to Italian Association Paediatric Hematology Oncology (AIEOP). Pharmacokinetic (PK) monitoring was applied by liquid chromatography-tandem mas...

Invasive fungal infections of the central nervous system (IFI‐CNS) are rare and life‐threatening complications in hematologic patients undergoing allogeneic hematopoietic stem cell transplantation (Allo‐HSCT). There is very few data on recent incidence and mortality of IFI‐CNS in allo‐HSCT and informations are very limited regarding effectiveness o...

Severe hepatic VOD/SOS is a potentially life-threatening complication of HCT conditioning that may also develop after high-dose chemotherapy. The most severe form of VOD/SOS is often accompanied by multi-organ failure (MOF) and is associated with a mortality rate of >80% when managed with supportive care alone. As part of the marketing authorizatio...

Background TRAIL, TNF-related apoptosis-induced ligand, is a novel biomarker of viral infection. In healthy individuals, circulating levels are typically ~ 80 pg/mL, but in the setting of viral infection, levels increase within hours. Recent studies have found decreased TRAIL levels to be correlated with disease severity in conditions such as cardi...

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 repo...

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. Th...

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...

Background Invasive Fungal Infections of the Central Nervous System (IFI‐CNS) are very rare and life threatening complications and no specific epidemiologic data are available in Allogeneic Hematopoietic Stem Cell Transplantation (Allo‐HSCT) recipients. Aims We describe the incidence, clinical characteristics and outcome of IFI‐CNS detected, over...

Invasive fungal infections (IFI) of the Central Nervous System (IFI‐CNS) and Paranasal Sinuses (IFI‐PS) are rare, life‐threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusin...

Introduction. The outcome of invasive fungal infections (IFI), particularly aspergillosis in acute leukemia (AL) patients (pts), has improved over the last years, but IFI still remain a major clinical issue in hematological pts, both for its severity and for the toxicity and potential drug interactions of antifungal treatments. Isavuconazole (ISV)...

Background Differentiating between viral and bacterial etiology is essential in order to enable the adequate use of antibiotics. Previous studies showed that TNF-related apoptosis induced ligand (TRAIL) can serve as a useful biomarker for distinguishing between bacterial and viral infections when combined with IP-10 and CRP (ImmunoXpert™). Here we...

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 pediatric oncological patients are limited. Objectives The infecti...

Background: Human herpesvirus (HHV-6) infection is increasingly recognized among allogeneic hematopoietic stem cell transplantation (HSCT) recipients, 30% being the risk of reactivation in the haploidentical setting. It has been associated with encephalitis, acute graft-versus-host disease (GvHD) and graft failure. Here we report two cohorts of pe...

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: 97 hematology-oncology pediatric patients with > 1 posaconazole plasma level (PPC) assessment in the first 6 weeks after...

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 rhabdomyosarcom...

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: multi-center, retrospective study to assess the incidence, outcome of proven and probable IFI (PP-IFI) in children treated for acute leukemia, non-Hod...

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 posi...

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...

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-versus-Host Disease in T-cell-replete transplants, and to delayed immune rebuilding due to T-cell-depletion in haploidentical transplantation.Methods We monitored...

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 gra...

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.ProcedureThis is a retrospective analysis on 12 patients with UNB under 18 ye...

Biochemical transduction networks can be modelled through a proper set of differential equations, and at the same time they can be experimentally analysed only by measuring a few signals at the end of the cascades. The study of those networks is of special importance in oncology.The approach proposed in this paper is aimed at characterising the net...

Two 8- and 9-year-old brothers were referred to the Pediatric Oncology Unit, Perugia General Hospital, because of hyperferritinemia. Both had a history of bilateral cataract and epilepsy. Genetic investigation revealed two distinct mutations in iron haemostasis genes; homozygosity for the HFE gene H63D mutation in the younger and heterozygosity in...

e21096 Background: Systems biology together with translational oncology is a new approach to discover sensitive pathways in specific cancers. In this study, we propose a computational modeling technique to investigate the possible effects various alterations, such as protein overexpression, gene amplification or mutations, may have on signaling, th...

Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8⁺ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8⁺ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain...

In adults, one-haplotype-mismatched haematopoietic SCT (haploidentical HSCT) is associated with slow immune recovery due to decaying thymic function and extensive T-cell depletion of the graft. Although essential for preventing GVHD, T-cell depletion underlies the major reasons for transplant failure: leukemia relapse and infections, with infection...

1013 Dendritic cells (DCs) play a pivotal role in initiating and modulating immune responses to pathogens. Data from experimental allogeneic bone marrow transplantation showed impaired DC function post-transplant as DCs produced mostly TNF-alfa with low amounts of IL-10, IL-12 and IFN-alpha, did not express co-stimulatory molecules upon activation...

Haploidentical transplantation, with extensive T cell depletion to prevent GvHD, is associated with a high incidence of infection-related deaths. The key challenge is to improve immune recovery with allogeneic donor T cells without triggering GvHD. As T regulatory cells (Tregs) controlled GvHD in pre-clinical studies, the present study evaluated th...

Hastening posttransplantation immune reconstitution is a key challenge in human leukocyte antigen (HLA)-haploidentical hematopoietic stem-cell transplantation (HSCT). In experimental models of mismatched HSCT, T-regulatory cells (Tregs) when co-infused with conventional T cells (Tcons) favored posttransplantation immune reconstitution and prevented...

The C-type lectin receptor Dectin-1 plays a pivotal role in antifungal immunity. In this study, the recently characterized human DECTIN1 Y238X early stop codon polymorphism leading to diminished Dectin-1 receptor activity was studied in relation to invasive aspergillosis susceptibility and severity in patients receiving hematopoietic stem cell tran...

Innate responses combine with adaptive immunity to generate the most effective form of anti-Aspergillus immune resistance. Whereas the pivotal role of dendritic cells in determining the balance between immunopathology and protective immunity to the fungus is well established, we determined that epithelial cells (ECs) also contributes to this balanc...

Every day we inhale thousands of tiny fungal spores (conidia), originating from many different fungal species such as Aspergillus, Cladosporium, Penicillium and Alternaria. Although these spores are packed with antigens and allergens, yet their inhalation does not continuously activate our innate immune cells or provoke inflammatory responses. By u...

We designed a phase I/II clinical study to determine safety and efficacy of thymosin alpha1 (Talpha1) administration in recipients of one HLA haplotype (haploidentical) stem cell transplants for hematologic malignancies. Talpha1 administration did not cause acute or chronic graft versus host disease and was associated with significant improvement i...

3525 Poster Board III-462 Recipients of allogeneic hematopoietic transplantation experience a slow reconstitution of donor-derived B and T cell number and function. This post-transplant period of immunodeficiency is associated with an increased risk of infection and malignant relapse. The developement of these complications notably correlates with...

The ability of the fungus Aspergillus fumigatus to activate, suppress, or subvert host immune response during life cycle in vivo through dynamic changing of cell wall structure and secretion implicates discriminative immune sensing of distinct fungal components. In this study, we have comparatively assessed secreted- and membrane-anchored proteins,...

The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10(9) per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus. Although these conidia contain many ant...

We analyzed the contribution of intracellular signaling to the functional plasticity of dendritic cells (DCs) presenting Candida albicans, a human commensal associated with severe diseases. Distinct intracellular pathways were activated by recognition of different fungal morphotypes in distinct DC subsets and in Peyer's patches DCs. Inflammatory DC...

Although the optimal donor for allogeneic hematopoietic stem cell transplantation is a human leukocyte antigen (HLA)-matched sibling, 75% of patients do not have a match and alternatives are matched unrelated volunteers, unrelated umbilical cord blood units, and full HLA-haplotype-mismatched family members. This review will focus on the open issues...

After haploidentical stem cell transplantation, immune recovery is slow due to decaying thymic function and extensive T-cell depletion of the graft which is needed to prevent Graft-versus-Host Disease (GvHD). Consequently, infectious related mortality is about 30–40%. To address this problem, we investigated the efficacy of adoptive immunotherapy a...

We describe two episodes of CMV retinitis in a pediatric patient who underwent a CD34+ selected graft from his haploidentical father. Both recipient and donor were cytomegalovirus (CMV) seropositive. Both episodes occurred late post-grafting during a phase of complete immunological recovery with sufficient numbers of circulating CMV-specific clones...

After haploidentical stem cell transplantation immune recovery is inevitably slow and infectious related mortality is about 30-40%. Immune reconstitution could be improved by infusing donor T cells, but the obstacle is graft-versus-host disease. In a mixed lymphocyte reaction, alloantigen-stimulated T cells uptake 4,5-dibromorhodamine methyl ester...

FoxP3(+) regulatory T (Treg) cells are important mediators of peripheral tolerance, and deficiency of this population is associated with autoimmune inflammation and onset of acute lethal graft-vs.-host disease in transplantation. Type I IFN-producing plasmacytoid dendritic cells (pDC) are implicated in the induction and maintenance of tolerance and...

We analyzed 112 patients with high-risk acute myeloid leukemia (61 in complete remission [CR]; 51 in relapse), who received human leukocyte-antigen (HLA)-haploidentical transplants from natural killer (NK) alloreactive (n = 51) or non-NK alloreactive donors (n = 61). NK alloreactive donors possessed HLA class I, killer-cell immunoglobulin-like rece...

Reactivation of latent human cytomegalovirus (HCMV) following allogeneic transplantation is a major cause of morbidity and mortality and predisposes to severe complications, including superinfection by Aspergillus species (spp). Antimicrobial polypeptides, including defensins and mannan-binding lectin, are known to block viral fusion by cross-linki...

Transplantation of peripheral blood hematopoietic cells from HLA haplotype-mismatched family members is a therapeutic strategy for patients with high-risk acute leukemia who need transplantation and do not have matched donors. As T cell alloreactions cause lethal GvHD in mismatched transplants, only T cell-depleted hematopoietic grafts can be used....

In haploidentical transplants that are KIR ligand mismatched in the GvH direction, functional donor NK-cells that express as their sole inhibitory receptor for self, a KIR for the HLA-class-I group which is absent in the recipient, sense the missing expression of the self class-I ligand on allogeneic targets and mediate alloreactions. In a limited...

Human NK cell function is regulated by clonally distributed inhibitory receptors termed "Killer cell Immunoglobulin-like Receptors" (KIRs) that recognize epitopes ("KIR ligands") shared by HLA-C and HLA-B class I allele groups and every functional NK cell in the repertoire expresses at least one receptor for self HLA-class I molecules. Consequently...

Thymosin alpha1 (Talpha1), a naturally occurring thymic peptide, primes dendritic cells (DCs) for antifungal T-helper type 1 resistance through Toll-like receptor 9 (TLR9) signaling. As TLR9 signaling also activates the immuno-suppressive pathway of tryptophan catabolism via indoleamine 2,3-dioxygenase (IDO), we examined Talpha1 for possible induct...