Francesca Compagno
@sanmatteo.org/site
Pediatrician Oncology and Hematology Department
Foundation IRCCS Policlinico San Matteo, Pavia, Italy
Scopus Publications
Scopus Publications
Daniele Zama, Andrea Zanaroli, Agnese Corbelli, Andrea Lo Vecchio, Margherita Del Bene, Antonella Colombini, Francesca Compagno, Angelica Barone, Ilaria Fontanili, Maria Rosaria D’Amico,et al.
Oxford University Press (OUP)
Abstract Objective The objective of this study was to assess the clinical impact and outcome of the SARS-CoV-2 infection on children with cancer or those who received a hematopoietic stem cell transplantation. Methods AIEOP (Italian Association of Pediatric Hematology and Oncology) performed a nationwide multicenter observational cohort study, including consecutive patients between April 2020 and November 2022. Results Twenty-five Italian centers participated and 455 patients were enrolled. We reported a significant increasing trend of symptomatic cases over the years, while the number of nonmild infections remained stable. Early infection after oncologic diagnosis (<60 days) and severe neutropenia were identified as independent risk factors for developing moderate, severe, or critical infections. The percentage of patients who were asymptomatic and mildly symptomatic and who stopped chemotherapy reduced over the years of the pandemic. Nine patients died, but no death was attributed to SARS-CoV-2 infection. Conclusions SARS-CoV-2 infection presented a self-limiting benign course in the Italian pediatric oncohematology population during the pandemic, and its main consequence has been the discontinuation of cancer-directed therapies. The rate of patients who were asymptomatic and stopped chemotherapy reduced over the years, suggesting that the continuation of chemotherapy is a feasible option.
Anne Bergeron, Malgorzata Mikulska, Julien De Greef, Louise Bondeelle, Tomas Franquet, Jean-Louis Herrmann, Christoph Lange, Isabel Spriet, Murat Akova, J Peter Donnelly,et al.
Elsevier BV
Daniele Zama, Francesco Baccelli, Antonella Colombini, Amalia Contino, Elisabetta Calore, Maria Grazia Petris, Linda Meneghello, Federico Mercolini, Andrea Lo Vecchio, Shana Montalto,et al.
Springer Science and Business Media LLC
Abstract 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 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed. Of the 153 SARS-Cov2 infections recorded, 100 were asymptomatic and 53 symptomatic. The course of COVID-19 was mild in 41, moderate in 2, severe in 5, and critical in 5 children. A total of 40.5% of patients were hospitalized, ten requiring oxygen support and 5 admitted to the intensive care unit. Antibiotics and steroids were the most used therapies. No patient died due to SARS-CoV-2 infection. Infections occurring early (< 60 days) after the diagnosis of the underlying disease or after SCT were associated to moderate, severe, and critical disease compared to infections occurring late (> 60 days) or during maintenance therapy. In the patients on active chemotherapy, 59% withdrew the treatment for a median of 15 days. SARS-CoV-2 presented a favorable outcome in children with cancer in Italy during the pandemic. Modification of therapy represents a major concern in this population. Our findings suggest considering regular chemotherapy continuation, particularly in patients on maintenance therapy or infected late after the diagnosis.
Simone Cesaro, Paola Muggeo, Daniele Zama, Monica Cellini, Katia Perruccio, Antonella Colombini, Francesca Carraro, Maria Grazia Petris, Valeria Petroni, Maurizio Mascarin,et al.
MDPI AG
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 in a scientifically correct communication with families and patients and to promote vaccination. The topics of the Consensus were: SARS-CoV-2 infection and disease (COVID-19) in the pediatric subjects; COVID-19 vaccines (type, schedule); who and when to vaccinate; contraindications and risk of serious adverse events; rare adverse events; third dose and vaccination after COVID-19; and other general prevention measures. Using the Delphi methodology for Consensus, 21 statements and their corresponding rationale were elaborated and discussed with the representatives of 31 centers, followed by voting. A high grade of Consensus was obtained on topics such as the potential risk of severe COVID-19 outcome in pediatric oncohematological patients, the need for vaccination as a preventative measure, the type, schedule and booster dose of vaccine, the eligibility of the patients for vaccination, and the timing, definition, and management of contraindications and serious adverse events, and other general prevention measures. All 21 of the statements were approved. This consensus document highlights that children and adolescents affected by hematological and oncological diseases are a fragile category. Vaccination plays an important role to prevent COVID-19, to permit the regular administration of chemotherapy or other treatments, to perform control visits and hospital admissions, and to prevent treatment delays.
Sheena Mukkada, Nickhill Bhakta, Guillermo L Chantada, Yichen Chen, Yuvanesh Vedaraju, Lane Faughnan, Maysam R Homsi, Hilmarie Muniz-Talavera, Radhikesh Ranadive, Monika Metzger,et al.
Elsevier BV
Background
Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer.
Methods
We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection.
Findings
Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020).
Interpretation
In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness.
Funding
American Lebanese Syrian Associated Charities and the National Cancer Institute.
Giulia Berzero, Giulia Campanini, Elisa Vegezzi, Matteo Paoletti, Anna Pichiecchio, Anna Maria Simoncelli, Anna Amelia Colombo, Paolo Bernasconi, Oscar Borsani, Angela Di Matteo,et al.
Ovid Technologies (Wolters Kluwer Health)
ObjectiveThe aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing.MethodsWe performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts.ResultsOf the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1.ConclusionsThe detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement.
Angela Guarina, Maddalena Marinoni, Giuseppe Lassandro, Paola Saracco, Silverio Perrotta, Elena Facchini, Lucia Dora Notarangelo, Giovanna Russo, Paola Giordano, Francesca Romano,et al.
Galenos Yayinevi
Objective: The association between celiac disease (CD) and immune thrombocytopenia (ITP) is still uncertain. The aim of this study was to characterize the coexistence of these two diseases in Italian children. Materials and Methods: This is a retrospective multicenter study investigating the occurrence of CD in 28 children with ITP diagnosed from January 1, 2000, to December 31, 2019. Results: The first diagnosis was ITP in 57.1% and CD in 32.1% of patients. In 3 patients (10.7%), the two diagnoses were simultaneous. All the potential and silent cases of CD in our cohort were diagnosed in the groups of “ITP first” and “simultaneous diagnosis”. In all children ITP was mild, and in 2 out of 8 not recovered from ITP at the time of CD diagnosis a normalization of platelet counts (>100,000/μL) occurred 3 and 5 months after starting a gluten-free diet, respectively. Conclusion: We think that screening for CD should be considered in children with ITP regardless of the presence of gastrointestinal symptoms. Furthermore, some patients may recover from ITP after starting a gluten-free diet.
Sabrina Basso, Francesca Compagno, Paola Zelini, Giovanna Giorgiani, Stella Boghen, Elena Bergami, Jessica Bagnarino, Mariangela Siciliano, Claudia Del Fante, Mario Luppi,et al.
Frontiers Media SA
Dramatic progress in the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from alternative sources in pediatric patients has been registered over the past decade, providing a chance to cure children and adolescents in need of a transplant. Despite these advances, transplant-related mortality due to infectious complications remains a major problem, principally reflecting the inability of the depressed host immune system to limit infection replication and dissemination. In addition, development of multiple infections, a common occurrence after high-risk allo-HSCT, has important implications for overall survival. Prophylactic and preemptive pharmacotherapy is limited by toxicity and, to some extent, by lack of efficacy in breakthrough infections. T-cell reconstitution is a key requirement for effective infection control after HSCT. Consequently, T-cell immunotherapeutic strategies to boost pathogen-specific immunity may complement or represent an alternative to drug treatments. Pioneering proof of principle studies demonstrated that the administration of donor-derived T cells directed to human herpesviruses, on the basis of viral DNA monitoring, could effectively restore specific immunity and confer protection against viral infections. Since then, the field has evolved with implementation of techniques able to hasten production, allow for selection of specific cell subsets, and target multiple pathogens. This review provides a brief overview of current cellular therapeutic strategies to prevent or treat pathogen-related complications after HSCT, research carried out to increase efficacy and safety, including T-cell production for treatment of infections in patients with virus-naïve donors, results from clinical trials, and future developments to widen adoptive T-cell therapy access in the HSCT setting.
Francesca Compagno, Sabrina Basso, Arianna Panigari, Jessica Bagnarino, Luca Stoppini, Alessandra Maiello, Tommaso Mina, Paola Zelini, Cesare Perotti, Fausto Baldanti,et al.
Frontiers Media SA
Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications of iatrogenic immune impairment after allogeneic hematopoietic stem cell transplantation (HSCT). In the pediatric setting, the majority of PTLDs are related to the Epstein–Barr virus (EBV) infection, and present as B-cell lymphoproliferations. Although considered rare events, PTLDs have been increasingly observed with the widening application of HSCT from alternative sources, including cord blood and HLA-haploidentical stem cell grafts, and the use of novel agents for the prevention and treatment of rejection and graft-vs.-host disease. The higher frequency initially paralleled a poor outcome, due to limited therapeutic options, and scarcity of controlled trials in a rare disease context. In the last 2 decades, insight into the relationship between EBV and the immune system, and advances in early diagnosis, monitoring and treatment have changed the approach to the management of PTLDs after HSCT, and significantly ameliorated the prognosis. In this review, we summarize literature on the impact of combined viro-immunologic assessment on PTLD management, describe the various strategies for PTLD prevention and preemptive/curative treatment, and discuss the potential of novel immune-based therapies in the containment of this malignant complication.
Simone Cesaro, Francesca Compagno, Daniele Zama, Linda Meneghello, Nagua Giurici, Elena Soncini, Daniela Onofrillo, Federico Mercolini, Rossella Mura, Katia Perruccio,et al.
Wiley
The infection by the new coronavirus-2019 (SARS-CoV-2) can be asymptomatic or mildly symptomatic in up to 80% of infected people, whereas the severe or lethal forms have been associated with several risk factors.1-3 Children with tumors represent a special risk group because treatment is frequently based on high-dose chemotherapy and, in leukemia and lymphoma, on steroids that result in severe impairment of innate and adaptive immunity. The effect of chemotherapy on an asymptomatic patient with SARS-CoV-2 infection is unknown, although a more severe course could be expected. During the epidemic peak in Italy, to prevent the hospital admission of asymptomatic infected patients, 14 pediatric hematology-oncology centers adopted a policy to screen the patients for SARS-CoV-2 by nasopharyngeal swab (NFS) before allowing them to start chemotherapy or enter hospital for supportive measures. Geographically, 10 centers were located in northern Italy, one in central Italy, and three in southern Italy/Isles. We report the results of this screening performed from February 20 to April 19, 2020. Follow-up data are as on April 30, 2020. At the start of screening, all centers were using the preventative measures recommended to contain the epidemic: social and physical distancing, use of hand hygiene, gloves, and surgical masks for patient, health personnel, and caregiver, screening of patients and parents for fever and signs or symptoms of respiratory tract infection, and restricted access by nonhealth personnel. A total of 334 NFS were performed on 247 patients with a median age at diagnosis of 7 years, range 0-17.9: 167 affected by leukemia or lymphoma and 80 with solid tumors. Eighty-nine patients (77%) were undergoing first-line chemotherapy, whereas 27 patients were receiving chemotherapy after relapse. At the time of NFS, the median and range of white blood cell, polimorphonuclear, hemoglobin, and platelet count or level were 3 × 109/L, 0.1-45.5, 1.33 × 109/L, 0-26.2, 11 g/L, 4-16, 21.9× 109/L, 12-865. NFS was positive in 10 of 334 (3%); all positives were in northern Italian centers where the epidemic wasmore prevalent; so the positive rate for the centers of north Italy was 10 of 291 NFS (3.4%). Among patients with positive NFS, eight were completely asymptomatic while two presentedwithmild fever. All positive patients ceased chemotherapy until NFS became negative, which occurred for nine patients after a median of 14 days (range 12-26 days), while one patient, who was undergoing both chemotherapy and radiotherapy, is still positive after 38 days. Two-week quarantine was performed at home (eight patients) or in hospital (two patients). In addition, a total of 56 NFS were performed in 35 stem cell transplant (SCT) patients (25 allogeneic and 10 autologous) affected by leukemia or lymphoma in 17 patients, solid tumors in 12 and nonmalignant hematology disease, or immunodeficiency in six. Themedian age at SCT was 9.6 years (range 0.3-17.6 years). The median time from SCT to NFS was 4.4 months (range 0-7.2 years). All 56 NFS were negative. In the Chinese epidemic, only 1% of infected people were younger than 10 years or 11-18 years old.2-4 Pediatric cases of COVID-19 overall had a good prognosis, because most of them were asymptomatic or withmild or moderate symptoms and only 2.5%were severely ill.4,5 The real incidence of asymptomatic infected people is unknown because it depends on how thoroughly the search is conducted but their identification and tracing are important to prevent the diffusion of infection. In this study, we found that the incidence of positive NFS in pediatric patients coming to hospital for chemotherapy was 3% for all centers, and 3.4% for the northern Italian centers. The main measure adopted for these patients was the postponing of chemotherapy until two NFS were negative at least 24 h apart. This precaution is in line with data on adult cancer patients showing that recent chemotherapy or oncology surgery was a risk factor for a more severe COVID-19 infection6 and with a case report of a severe respiratory form of COVID-19 in a Chinese child with T-cell acute leukemia.7 The impact of chemotherapy on the risk of progression of an asymptomatic or mildly symptomatic SARS-CoV-2 infection toward a severe or lethal form of COVID-19 is not really known. In a multicenter survey among pediatric oncology centers, only nine out of 200 symptomatic or suspected patients tested positive for SARSCoV-2 at NFS. None of them required intensive care or ventilatory support, and only two patients were treated with hydroxychloroquine together with lopinavir/ritonavir in one patient.8 The low morbidity documented so far in pediatric hematology-oncology patients raises the question about the risk/benefit ratio of interrupting or postponing chemotherapy in asymptomatic or mildly symptomatic SARS-CoV2-positive patients. Interestingly, all the SCT patients tested negative. This could be due to the smaller number of patients assessed or to the fact that SCT patients are more accustomed to adopting preventative measures. In conclusion, SARS-CoV-2 can result in asymptomatic infections in patients undergoing chemotherapy and their identification is important to preserve a hospital unit clean from COVID-19 cases. Further studies are needed to define the least-risky chemotherapy
Andrea Ferrari, Marco Zecca, Carmelo Rizzari, Fulvio Porta, Massimo Provenzi, Maddalena Marinoni, Richard Fabian Schumacher, Roberto Luksch, Monica Terenziani, Michela Casanova,et al.
Wiley
To the Editor: This report assesses the impact of theCOVID-19pandemic onpediatric cancer patients over an 8-week period elapsing from the day of the Italian outbreak (February 20, 2020) to the time of writing (April 15, 2020) in Lombardia region, the epicenter of the pandemic in Italy and one of the worst-hit areas in Europe. During the 8-week period, 155467 confirmedCOVID-19 diagnoses and 19508deaths due to the virus were reported in Italy, while Lombardia registered 63 098 positive cases (40% of all Italians affected) and 11 384 deaths. Lombardia is the central region of northern Italy, covering an area of 23 863 km2 with a population of 10 million (population density 421.6/km2). The region has six pediatric onco-hematology centers. Cancer incidence in the region’s population aged 0-18 years is approximately 19/100 000, with 320 new cases expected to occur each year.1 In addition, 40-50%additional patients come fromother Italian regions (often from the south) or from abroad. In the days following the outbreak, the pediatric oncology centers in the region were suddenly faced with an unexpected emergency situation exceeding the capacity of Lombardia’s health system2 and had to urgently adjust accordingly: they continued to develop oncological treatments, while implementing measures to minimize the risks of infections, to test for COVID-19 high-risk cases and to adequately manage COVID-19-positive patients,3 as reported in Table 1. In all, in the study period, there were 347 accesses for inpatients registered by the six centers and 4138 for outpatients (total 4485). Most patients accessed a center multiple times during the 8-week period. Overall, 286 patients were tested for COVID-19, 212 of them asymptomatic (187 tested for screening purposes and 25 due to close contact with diagnosed cases) and 74 symptomatic (Table 2). Twenty-one cases of COVID-19 infection were identified (48% of themmales), with amedian age of 6 years (range1-17). In particular, six cases emerged from among the 187 patients screened, six among the 25 tested due to close contact with diagnosed cases, and nine among the 74 patients tested because they had flu-like symptoms. Tumor types of the 21 positive cases were as follows: 10 leukemias, five soft tissue or bone sarcomas, two lymphomas, two hepatoblastomas, one central nervous system tumor, and one colon carcinoma. Fifteen of these patients were on treatment, and six had completed their treatment andwere in followup. Thepatients’ cancer treatmentsweremodified in 10 cases (delaying chemotherapy or reducing drug doses, postponing surgery). Two patients experienced complications of the viral TABLE 1 Measures implemented during the COVID-19 pandemic by the six pediatric onco-hematology centers in Lombardia a
Marie von Lilienfeld-Toal, , Jörg Janne Vehreschild, Oliver Cornely, Livio Pagano, Francesca Compagno, and Hans H. Hirsch
Springer Science and Business Media LLC
AbstractSince early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.
Elisa Vegezzi, Giulia Berzero, Desiree Barbetta, Anna Amelia Colombo, Oscar Borsani, Paolo Bernasconi, Francesca Compagno, Marco Zecca, Giulia Campanini, Anna Simoncelli,et al.
Springer Science and Business Media LLC
The aim of this study was to review the quality of the diagnostic work-up for acute encephalitis carried out at our center in a cohort of patients with hematological disorders. Our data showed substantial heterogeneity in investigating patients. Not all patients had their CSF tested for viruses commonly responsible for encephalitis in immunocompetent individuals (e.g., VZV, enterovirus). A blood sample for the calculation of the CSF/blood replication ratio was collected in 74% of cases. CSF cultures and immunophenotyping of CSF cells were performed in 77% and 21% of patients, respectively. A multidisciplinary consensus is needed to improve current guidelines and standardize diagnostic protocols.
Gianni Bisogno, Massimo Provenzi, Daniele Zama, Annalisa Tondo, Cristina Meazza, Antonella Colombini, Federica Galaverna, Francesca Compagno, Francesca Carraro, Raffaela De Santis,et al.
Oxford University Press (OUP)
Abstract Background Little is known as yet about the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children being treated for cancer. Methods We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 female and 13 male; median age, 7 years [range, 0–16 years]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (n = 26), or after stem cell transplantation (n = 3) during the peak of the epidemic in Italy. These patients suffered from leukemia (n = 16), lymphoma (n = 3), solid tumors (n = 10), and Langerhans cell histiocytosis (n = 1). Results The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir. Among the 26 patients on chemotherapy/immunotherapy, the treatment was suspended in 16 cases for a median of 26 days (range, 15–68 days), whereas 8 patients continued their chemotherapy and 2 had minor modifications to their treatment regimen. Conclusions SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.
Federica Ferulli, Matteo Tanzi, Ilaria Turin, Enrica Montini, Vittorio Rosti, Gloria Acquafredda, Daniela Lisini, Francesca Compagno, Stella Boghen, Amelia Licari,et al.
Elsevier BV
BACKGROUND
The Wilms tumor antigen 1 (WT1) is over-expressed in a vast majority of adult and childhood acute leukemia and myelodysplastic syndromes, being lowly or transiently expressed in normal tissues and hematopoietic stem cells (HSCs). A number of HLA-restricted WT1 epitopes are immunogenic, allowing the in vitro induction of WT1-specific cytotoxic T lymphocytes (CTLs) from patients and healthy donors.
AIM
The aim of the study was to investigate the feasibility of producing WT1-specific CTLs suitable for somatic cell therapy to prevent or treat relapse in children with acute myeloid or lymphoblastic leukemia given haploidentical HSC transplantation (haplo-HSCT).
METHODS
For WT1-specific CTL production, donor-derived either peripheral blood mononuclear cells (PBMCs) or CD8+ lymphocytes were stimulated with WT1 peptide-loaded donor dendritic cells in the presence of interleukin (IL)-7 and IL-12. Effector cells were re-stimulated once with irradiated donor PBMCs pulsed with WT1-peptides, and then expanded in an antigen-independent way.
RESULTS
WT1-specific CTLs, displaying high-level cytotoxicity against patients' leukemia blasts and negligible activity against patients' non-malignant cells, were obtained from both PBMCs and CD8+ lymphocytes. WT1-specific CTLs obtained from PBMCs showed a better expansion capacity and better anti-leukemia activity than those obtained from CD8+ lymphocytes, even though the difference was not statistically significant. In CTLs derived from PBMCs, both CD8+ and CD4+ subpopulations displayed strong anti-leukemia cytotoxic activity.
DISCUSSION
Results of this pre-clinical study pave the way to a somatic cell therapy approach aimed at preventing or treating relapse in children given haplo-HSCT for WT1-positive leukemia.
Francesca Compagno, Klaudia Naegele, Christian R. Kahlert, Irene Hsli, Karoline Aebi-Popp, Begona Martinez de Tejada, Paolo Paioni, Sabine Yerly, Jrg Bni, Manuel Battegay,et al.
EMH Swiss Medical Publishers, Ltd.
AIMS OF THE STUDY
Combination antiretroviral therapy (cART) has reduced mother-to-child transmissions (MTCT) and improved the prognosis of HIV-infected newborns. However, drug resistance mutations (DRM) in HIV-infected children, either transmitted by MTCT (HIV-tDRM) or selected by suboptimal adherence and drug levels (HIV-sDRM), remain a concern. We sought to determine the rate of HIV-tDRM and HIV-sDRM in MTCT pairs in Switzerland.
METHODS
We performed a retrospective analysis of prospectively collected clinical data and available stored samples from MTCT pairs participating in the Swiss Mother-Child HIV (MoCHIV) cohort.
RESULTS
We identified 22 HIV-infected mother-child pairs with delivery between 1989 and 2009 who had 15 years of follow-up (33% white ethnicity). Twenty-one women (96%) were treatment-naïve before pregnancy, 8 (36%) had an unknown HIV status and delivered vaginally, 2 were diagnosed but not treated, and 11 (50%) received antiretrovirals during pregnancy or at delivery, of whom only 6 cases (27%) had cART. HIV subtypes were concordant in all mother-child pairs (subtype B 13/22 [59%]). Using stored plasma (n = 66) and mononuclear cell (n = 43) samples from the children, HIV-tDRM (M184V) was identified in 1 of 22 (4.5%) mothers (1/11 treated, 9%) and was followed by HIV-sDRM at 10 months of age. HIV-sDRM (M184V 23%; K103N 4.5%; D67N 13.6%) occurred in 16/22 (73%) after 4 years, half of whom were treatment naïve. HIV-sDRM were associated with a lower CD4 T-cell nadir (p <0.05) and tended to have higher viral loads and more frequent cART changes.
CONCLUSIONS
HIV-tDRM were low in this Swiss MoCHIV cohort, making them a minor yet preventable complication of prenatal HIV care, whereas HIV-sDRM are a significant challenge in paediatric HIV care.
Yasmin Spahr, Sarah Tschudin-Sutter, Veronika Baettig, Francesca Compagno, Michael Tamm, Jörg Halter, Sabine Gerull, Jakob Passweg, Hans H Hirsch, and Nina Khanna
Oxford University Press (OUP)
Abstract Background Paramyxoviruses include respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (MPV), which may cause significant respiratory tract infectious disease (RTID) and mortality after allogeneic hematopoietic cell transplantation (HCT). However, clinical data regarding frequency and outcome are scarce. Methods We identified all paramyxovirus RTIDs in allogeneic HCT recipients diagnosed by multiplex polymerase chain reaction between 2010 and 2014. Baseline characteristics of patients, treatment, and outcome of each episode were analyzed; ie, moderate, severe, and very severe immunodeficiency (verySID) according to HCT ≤6 months, T- or B-cell depletion ≤3 months, graft-versus-host disease, neutropenia, lymphopenia, or hypo-gammaglobulinemia. Results One hundred three RTID episodes in 66 patients were identified (PIV 47% [48 of 103], RSV 32% [33 of 103], MPV 21% [22 of 103]). Episodes occurred in 85% (87 of 103) at &gt;100 days post-HCT. Lower RTID accounted for 36% (37 of 103). Thirty-nine percent (40 of 103) of RTID episodes required hospitalization and more frequently affected patients with lower RTID. Six percent progressed from upper to lower RTID. Overall mortality was 6% and did not differ between paramyxoviruses. Sixty-one percent (63 of 103) of episodes occurred in patients with SID, and 20.2% (19 of 63) of episodes occurred in patients with verySID. Oral ribavirin plus intravenous immunoglobulin was administered in 38% (39 of 103) of RTIDs, preferably for RSV or MPV (P ≤ .001) and for SID patients (P = .001). Patients with verySID frequently progressed to lower RTID (P = .075), required intensive care unit transfer, and showed higher mortality. Conclusion Paramyxovirus RTID remains a major concern in allogeneic HCT patients fulfilling SID and verySID, emphasizing that efficacious and safe antiviral treatments are urgently needed.
Michela Cioni, Arcangelo Nocera, Annalisa Innocente, Augusto Tagliamacco, Antonella Trivelli, Sabrina Basso, Giuseppe Quartuccio, Iris Fontana, Alberto Magnasco, Francesca Drago,et al.
Hindawi Limited
De novo posttransplant donor-specific HLA-antibody (dnDSA) detection is now recognized as a tool to identify patients at risk for antibody-mediated rejection (AMR) and graft loss. It is still unclear whether the time interval from transplant to DSA occurrence influences graft damage. Utilizing sera collected longitudinally, we evaluated 114 consecutive primary pediatric kidney recipients grafted between 2002 and 2013 for dnDSA occurrence by Luminex platform. dnDSAs occurred in 39 patients at a median time of 24.6 months. In 15 patients, dnDSAs developed within 1 year (early-onset group), while the other 24 seroconverted after the first posttransplant year (late-onset group). The two groups were comparable when considering patient- and transplant-related factors, as well as DSA biological properties, including C1q and C3d complement-binding ability. Only recipient age at transplant significantly differed in the two cohorts, with younger patients showing earlier dnDSA development. Late AMR was diagnosed in 47% of the early group and in 58% of the late group. Graft loss occurred in 3/15 (20%) and 4/24 (17%) patients in early- and late-onset groups, respectively (p = ns). In our pediatric kidney recipients, dnDSAs predict AMR and graft loss irrespective of the time elapsed between transplantation and antibody occurrence.
Alberto Verrotti, Maria Valentina Spartà, Debora Monacelli, Rossella Porto, Miriam Castagnino, Annalisa Russo Raucci, Francesca Compagno, Simona Viglio, Thomas Foiadelli, Francesco Nicita,et al.
Wiley
Epilepsy in Ehlers‐Danlos syndrome (EDS) has been reported in the literature, but there are no studies that have investigated in detail clinical and electroencephalography (EEG) features in patients with EDS, and that have compared the outcome of epilepsy in subjects with or without brain lesions. We report a series of 42 patients with EDS and epilepsy, including data that concern clinical characteristics, EEG abnormalities, brain malformations at magnetic resonance imaging (MRI) and long‐term outcome.