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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.
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COVID-19 , Enfermedades Transmisibles , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Niño , Humanos , SARS-CoV-2 , Neoplasias/complicaciones , Neoplasias/terapia , Neoplasias/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Background: Infant leukemia is a rare form of acute leukemia diagnosed prior to the age of 1 and is characterized by an extremely poor prognosis due to its dismal response to current therapeutic approaches. It comprises about 4% of all childhood cases of acute lymphoblastic leukemia (ALL). Isolated initial cutaneous involvement in ALL is uncommon, and even more so in infant ALL. Case presentation: Here, we present the case of a 2-month-old healthy-appearing infant, initially presenting with a single scalp nodule and subsequently diagnosed with an infant ALL. The leukemia was characterized by the most immature B-lineage immunophenotype [pro-B ALL/B-I, according to the European Group for the Immunological Characterization of Leukaemias (EGIL) classification] and chromosomal translocation t(9;11)(p22;q23), resulting in fusion gene KMTLA2::MLLT3, which is considered a negative prognostic factor. The patient underwent hematopoietic stem cell transplantation and is still in remission. Conclusions: This case is peculiar because of the rare occurrence of isolated initial cutaneous involvement in ALL. Despite the healthy appearance of the patient, every suspicious symptom suggestive of malignancies should be further investigated to anticipate the diagnosis and start treatment early.
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Hematopoietic stem cell transplantation (HSCT) represents a curative option for pediatric patients affected by malignant and non-malignant disorders. Several complications may arise during the post-transplantation period, including immune-mediated disorders. Immune-mediated cytopenias (IMCs) account for up to 22% of pediatric HSCT complications, representing an important cause of morbidity and mortality post-HSCT. So far, their pathogenesis is not well-understood, and their management may be very challenging. Further, most patients are refractory to first-line treatment which is based on high-dose intravenous steroids, immunoglobulin, and the monoclonal anti-CD20 antibody - rituximab. No clear consensus has been reached for second- and third-line therapeutic options. CONCLUSION: We reviewed the epidemiology, risk factors, pathogenesis, and treatment of IMCs, aiming to offer a deeper understanding of these complications as a guide to improving the management of these fragile patients and a cue for the design of tailored clinical trials. WHAT IS KNOWN: ⢠IMCs arising in the post-HSCT setting represent a rare but potentially life-threatening complication. Younger patients affected by non-malignant disorders are at the greatest risk of IMCs arising after HSCT. Corticosteroids, intravenous immunoglobulin, and rituximab represent the undiscussed first-line therapeutic approach. WHAT IS NEW: ⢠This review highlitghts how children present unique risk factors for post HSCT IMCs, which are the result of the complex relationship between the immaturity of their infantile immune system and all the perturbing agents and factors which characterize the post-HSCT setting. Future efforts are warranted to establish the best option for refractory patients, for whom a standard and validated approach is not currently available. Among new agents, ibrutinib or bortezomib and fostamatinib or low-dose IL-2 could represent a good therapeutic option for patients with graft-versus-host disease and hemolytic anemia or graft-versus-host disease and thrombocytopenia, respectively.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trombocitopenia , Humanos , Niño , Rituximab/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/terapia , Trombocitopenia/etiología , Factores de RiesgoRESUMEN
Beckwith-Wiedemann Syndrome (BWS) is a pediatric overgrowth disorder involving a predisposition to embryonal tumors. Most of the tumors associated with BWS occur in the first 8-10 years of life, and the most common is Wilms tumor (WT). BWS clinical heterogeneity includes subtle overgrowth features or even silent phenotypes, and WT may be the presenting symptom of BWS. WT in BWS individuals exhibit distinct characteristics from those of sporadic WT, and the management of these patients needs a peculiar approach. The most important feature is a higher risk of developing bilateral disease at some time in the course of the illness (synchronous bilateral disease at diagnosis or metachronous recurrence after initial presentation with unilateral disease). Accordingly, neoadjuvant chemotherapy is the recommended approach also for BWS patients with unilateral WT to facilitate nephron-sparing surgical approaches. This review emphasizes the importance of early BWS recognition, particularly if a WT has already occurred, as this will result in an urgent consideration of first-line cancer therapy.
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Mesenchymal stem cells (MSCs) are classified as advanced therapy medicinal products, a new category of GMP (good manufacturing practice)-compliant medicines for clinical use. We isolated MSCs from 5 bone marrow (BM) samples using human platelet lysate (HPL) instead of foetal bovine serum (FBS). We used a new method of HPL production consisting of treating platelet (PLTs) pools with Ca-Gluconate to form a gel clot, then mechanically squeezing to release growth factors. We compared the new HPL (HPL-S) with the standard (HPL-E) obtained by freezing/thawing cycles and by adding heparin. HPL-S had not PLTs and fibrinogen but the quantity of proteins and growth factors was comparable to HPL-E. Therefore, HPL-S needed fewer production steps to be in compliance with GMP conditions. The number of colonies forming unit-fibroblasts (CFU-F) and the maintenance of stem markers showed no significant differences between MSCs with HPL-E and HPL-S. The cumulative population doubling was higher in MSCs with HPL-E in the earlier passages, but we observed an inverted trend of cell growth at the fourth passage. Immunophenotypic analysis showed a significant lower expression of HLA-DR in the MSCs with HPL-S (1.30%) than HPL-E (14.10%). In conclusion, we demonstrated that HPL-S is an effective alternative for MSC production under GMP conditions.
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Células Madre Mesenquimatosas , Plaquetas/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Medios de Cultivo/metabolismo , Humanos , Inmunofenotipificación , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
Purpose: The purpose of the study was to create in Italian a transition protocol survey to monitor the readiness of childhood, adolescent, and young adult (CAYA) cancer survivors who are undergoing transition from pediatric to adult health care. A protocol could support clinical practice through the proposal of individualized transition care pathways for CAYA survivors and inform future scientific studies that focus on barriers to successful transition. Methods: Three international questionnaires that investigate the biopsychosocial issues and needs of survivors were subjected to the Forward and Backward Translation process. Following this, CAYA survivors were recruited from September 2019 to August 2020 in the pediatric oncology centers of the Interregional Pediatric Oncology Network of Piedmont and the Aosta in Italy to participate in cognitive interviews as part of the validation and cultural adaptation process of the questionnaires, which will form the transition protocol survey. Results: Revisions and cognitive interviews with 40 CAYA survivors identified any inadequate expressions and resolved any concepts of misunderstanding or cultural unsuitability for the Italian translation. Overall, they found the scales to be easily understandable, and an Italian version of the scales was produced to create the final transition protocol survey. Conclusion: The transition protocol survey might be used as a valid tool to highlight critical issues to support sustainable transition processes between Italian oncology centers. The protocol can be implemented into clinical practice thus offering CAYA the possibility of resolving some needs, receiving personalized support, and surveillance before the transition.
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Supervivientes de Cáncer , Neoplasias , Adolescente , Supervivientes de Cáncer/psicología , Niño , Atención a la Salud , Humanos , Neoplasias/psicología , Neoplasias/terapia , Encuestas y Cuestionarios , Sobrevivientes , Adulto JovenRESUMEN
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated HLA-mismatched donor (MMUD) is one of the alternatives where an HLA-matched donor is not found. The aim of this study was to compare bone marrow (BM) versus peripheral blood stem cells (PBSC) as hematopoietic rescue following allogeneic unrelated mismatched stem cell transplantation (MMUD). METHODS: The patients were divided into two groups: 43 pediatric patients were treated with BM and 17 pediatric patients with PBSC. The study was registered at ClinicalTrials.gov NCT04598789. RESULTS: The 3-year Overall Survival (OS) was 74% versus 31% (p = .0011). Transplant related mortality (TRM) was 16% versus 33% (p = .025), and relapse incidence (RI) was 16% versus 35% (p = .005). The day-100 acute Graft-versus-host disease (GvHD) incidence grade II-IV and III-IV was 30% versus 28% (p = NS) and 17% versus 17% (p = NS). The 3-year chronic GvHD incidence was 22% versus 33% (p = NS). CONCLUSION: Despite all the limits of this retrospective study we were able to show how the combination of BM and ATG is able to prevent GvHDs and guarantee a high OS. Future studies addressing the issue of a post-transplant cellular therapy approach may potentially reduce relapses when GvHD is absent.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Células Madre de Sangre Periférica , Médula Ósea , Niño , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Recurrencia Local de Neoplasia/etiología , Estudios Retrospectivos , Donante no EmparentadoRESUMEN
A 12-year-old male being treated for a high-risk relapsed T-acute lymphoblastic leukemia presented progressive weakness and numbness of both legs after having received a chemotherapy regimen that included bortezomib. Diagnosis of acute Guillain-Barré syndrome-like inflammatory demyelinating polyneuropathy was made following clinical examination, cerebrospinal fluid analysis, electrodiagnostic studies, magnetic resonance imaging, and serum immunoglobulin antibodies to anti-ganglioside. Intravenous immunoglobulin treatment was started, resulting in complete clinical recovery. Although in rare cases, Guillain-Barré syndrome after bortezomib therapy has been reported; this paper suggests that GBS may occur when bortezomib is administered and highdose intravenous immunoglobulin lead to a resolution of the symptoms.
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Síndrome de Guillain-Barré , Leucemia-Linfoma Linfoblástico de Células Precursoras , Bortezomib/efectos adversos , Niño , Síndrome de Guillain-Barré/inducido químicamente , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/tratamiento farmacológico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
A timely and effective immune reconstitution after hematopoietic stem cell transplantation (HSCT) is of crucial importance to enhance graft-versus-leukemia reaction in hematological malignancies. Several factors can influence the yield of this process, and new mathematical models are needed to describe this complex phenomenon. METHODS: We retrospectively analyzed immune reconstitution in the early post-HSCT period in a multicenter cohort of 206 pediatric patients affected by acute lymphoblastic leukemia, acute myeloblastic leukemia, and myelodysplastic syndrome who received their first allo-HSCT. All patients were in complete morphological remission at transplantation and were followed-up at least 26 mo post-HSCT. Blood samples for analysis of lymphocyte subset numbers were collected at day 100 (±20 d). RESULTS: The 2-y cumulative incidence of relapse was 22.2% (95% confidence interval [CI], 17.3-27). Using principal component analysis, we identified based on 16 input variables a new multivariate model that enables patients' description in a low-dimensional model, consisting of the first 2 principal components. We found that the numbers of CD3+/CD4+/CD8+ lymphocyte subsets at day 100 post-HSCT and acute graft-versus-host disease had the greatest impact in preventing relapse. We ultimately derived a risk score defining high- or medium-low-risk groups with 2-y cumulative incidence of relapse: 35.3% (95% CI, 25.6-45) and 15.6% (95% CI, 10.1-20.7), respectively (P = 0.001*). CONCLUSIONS: Our model describes immune reconstitution and its main influencing factors in the early posttransplantation period, presenting as a reliable model for relapse risk prediction. If validated, this model could definitely serve as a predictive tool and could be used for clinical trials or for individualized patient counseling.
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Abdomen/diagnóstico por imagen , Enfermedad Injerto contra Huésped/diagnóstico por imagen , Enfermedades Intestinales/diagnóstico por imagen , Ultrasonografía/métodos , Adrenoleucodistrofia/terapia , Beclometasona/uso terapéutico , Niño , Glucocorticoides/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Enfermedades Intestinales/tratamiento farmacológico , Masculino , Nitrilos/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Trasplante de Células Madre/métodos , Ultrasonografía Doppler en ColorRESUMEN
Technology-enhanced simulation has emerged as a great educational tool for pediatric education. Indeed, it represents an effective method to instruct on technical and non-technical skills, employed by a large number of pediatric training programs. However, this unique pandemic era posed new challenges also on simulation-based education. Beyond the mere facing of the clinical and societal impacts, it is fundamental to take advantage from the current changes and investigate innovative approaches to improve the education of pediatric healthcare professionals. To this aim, we herein lay down the main pillars that should support the infrastructure of the future technology-enhanced simulation.
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Competencia Clínica , Simulación por Computador/tendencias , Educación de Postgrado en Medicina/métodos , Pediatría/educación , Entrenamiento Simulado/tendencias , Niño , HumanosAsunto(s)
Tratamiento Farmacológico de COVID-19 , Coinfección/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/efectos adversos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Adenosina Monofosfato/administración & dosificación , Adenosina Monofosfato/análogos & derivados , Alanina/administración & dosificación , Alanina/análogos & derivados , Anfotericina B/administración & dosificación , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/virología , Coinfección/diagnóstico , Coinfección/inmunología , Coinfección/microbiología , Quimioterapia Combinada/métodos , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/administración & dosificación , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/inmunología , Aspergilosis Pulmonar Invasiva/microbiología , Pulmón/diagnóstico por imagen , Masculino , Metilprednisolona/administración & dosificación , Agonistas Mieloablativos/administración & dosificación , Agonistas Mieloablativos/efectos adversos , Nitrilos , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pirazoles/administración & dosificación , Pirimidinas , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Multiple investigators have described an increased incidence of thromboembolic events in SARS-CoV-2-infected individuals. Data concerning hemostatic complications in children hospitalized for COVID-19/multisystem inflammatory syndrome in children (MIS-C) are scant. OBJECTIVES: To share our experience in managing SARS-CoV-2-associated pro-coagulant state in hospitalized children. METHODS: D-dimer values were recorded at diagnosis in children hospitalized for SARS-CoV-2-related manifestations. In moderately to critically ill patients and MIS-C cases, coagulation and inflammatory markers were checked at multiple time points and median results were compared. Pro-thrombotic risk factors were appraised for each child and thromboprophylaxis was started in selected cases. RESULTS: Thirty-five patients were prospectively enrolled. D-dimer values did not discriminate COVID-19 of differing severity, whereas were markedly different between the COVID-19 and the MIS-C cohorts. In both cohorts, D-dimer and C-reactive protein levels increased upon clinical worsening but were not accompanied by decreased fibrinogen or platelet values, with all parameters returning to normal upon disease resolution. Six patients had multiple thrombotic risk factors and were started on pharmacological thromboprophylaxis. No deaths or thrombotic or bleeding complications occurred. CONCLUSIONS: COVID-19 pediatric patients show mildly altered coagulation and inflammatory parameters; on the other hand, MIS-C cases showed laboratory signs of an inflammatory driven pro-coagulant status. Universal anticoagulant prophylaxis in hospitalized children with SARS-CoV-2-related manifestations is not warranted, but may be offered to patients with other pro-thrombotic risk factors in the context of a multi-modal therapeutic approach.