Internal Consistency and Floor/Ceiling Effects of the Gross Motor Function Measure for Use with Children Affected by Cancer: A Cross-Sectional Study.

Children/adolescents with cancer can develop adverse effects impacting gross motor function. There is a lack of gross motor function assessment tools that have been validated for this population. The aim of this multicenter cross-sectional study was to preliminary validate the 88-item Gross Motor Function Measure (GMFM-88) for use in children/adolescents with cancer, exploring internal consistency and floor/ceiling effect.

Interleukin-1 blockade in patients with Wiskott-Aldrich syndrome: a retrospective multinational case series.

Up to 70% of patients with Wiskott-Aldrich syndrome (WAS) develop autoimmune and inflammatory manifestations. Dysregulation of interleukin 1 (IL-1) may be involved in their pathogenesis, yet there is little evidence on treatment with anti-IL-1 agents in these patients. We conducted a multicenter retrospective analysis of 9 patients with WAS treated with anti-IL-1 agents (anakinra or canakinumab).

An expert consensus on prevention, diagnosis, and management of hemorrhagic cystitis in pediatric hematopoietic cell transplantation, on behalf of the Infectious Disease and Hematopoietic Cell Transplant Working groups of Italian Pediatric Hematology Oncology Association (AIEOP).

The optimal management of hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HCT) is debated, both for early onset HC (EOHC) secondary to chemotherapy toxicity and BK Polyomavirus (BKPyV)-related HC, due to the lack of controlled trials, particularly referred to pediatric setting. Actually, clinical practice is mainly based on guidelines of the European Conference on Infections in Leukemia, 6 edition, which considers both adult and pediatric populations but concludes that, despite much progress in understanding the pathogenesis, epidemiology, and risk factors, this complication still represents a disabling unmet clinical need with limited prophylactic and therapeutic options. Additionally, the Guidelines of the American Society of Clinical Oncology define the management of chemotherapeutic toxicity independently from the patients' population.

Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation for Children with High-Risk Neuroblastoma Using a Reduced-Intensity Conditioning Regimen: Results from the AIEOP Trial.

Despite aggressive multimodal treatment, the outcomes of pediatric patients with high-risk (HR) neuroblastoma (NB) remain poor. The rationale for allogeneic hematopoietic stem cell transplantation (allo-HCT) to treat NB was based on the possible graft-versus-tumor effect; however, toxicity limits its efficacy. We sought to prospectively assess the feasibility and efficacy of allo-HCT using a reduced-intensity conditioning regimen in pediatric patients with HR NB in a multicenter phase II trial.

Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency.

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34 cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT.

From the identification of actionable molecular targets to the generation of faithful neuroblastoma patient-derived preclinical models.

Background: Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Although the overall survival of patients with NB has improved in the last years, more than 50% of high-risk patients still undergo a relapse. Thus, in the era of precision/personalized medicine, the need for high-risk NB patient-specific therapies is urgent.

Improving Drug Safety in Pediatric and Young Adult Patients with Hemato-Oncological Diseases: A Prospective Study of Active Pharmacovigilance.

The acquisition of relevant pediatric clinical safety data is essential to ensure tolerable drug therapies. Comparing the real number of Adverse Drug Reaction (ADR) reports in clinical practice with the literature, the idea of ADR underreporting emerges. An active pharmacovigilance observational prospective study was conducted to assess the safety of oncology pharmacological prescriptions in patients aged 0-24 years at Institute for Maternal and Child Health IRCCS Burlo Garofolo in Trieste and IRCCS CRO National Cancer Institute in Aviano (Italy) between January 2021 and October 2023.

Donor Cell Acute Myeloid Leukemia after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease: A Case Report and Literature Review.

The patient reported here underwent hematopoietic stem cell transplantation (HSCT) due to chronic granulomatous disease (CGD) caused by biallelic mutations of the NCF1 gene. Two years later, he developed AML, which was unexpected and was recognized via sex-mismatched chromosomes as deriving from the donor cells; the patient was male, and the donor was his sister. Donor cell leukemia (DCL) is very rare, and it had never been reported in patients with CGD after HSCT.

Neck stiffness and bone osteolytic lesion in a 3-years old child: a case report.

Background: Neuroblastoma is the most frequent extracranial solid tumor occurring in childhood, representing approximately 28% of all cancers diagnosed in infants. Signs and symptoms of neuroblastoma vary with the site of development of the tumor and can mimic other diseases due to its extreme clinical variability. However, torticollis is not reported in the medical literature as a leading symptom of neuroblastoma.

A "SURFin' Leukemia": Acute Lymphoblastic Leukemia Masquerading as a Syndrome of Undifferentiated Recurrent Fever.

Periodic fever is not uncommon in childhood and is often ascribed to autoinflammatory conditions; however, it may be present also in children with cancer. We here describe the case of a 3-year-old boy with acute lymphoblastic leukemia who initially presented with a 4-month history of recurrent, stereotyped episodes of fever and localized joint pain, separated by completely symptom-free intervals. These symptoms were initially interpreted as a possible syndrome of undifferentiated recurrent fever until more signs of leukemia became apparent.

Impact of Mercaptopurine Metabolites on Disease Outcome in the AIEOP-BFM ALL 2009 Protocol for Acute Lymphoblastic Leukemia.

In the maintenance phase of Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)- Berlin-Frankfurt-Muenster (BFM) acute lymphoblastic leukemia (ALL) 2009 protocol, mercaptopurine (MP) is given at the planned dose of 50 mg/m /day; however, dose adjustments are routinely performed to target patients' white blood cells to the optimal range of 2,000-3,000 cells/μL. Pediatric patients with ALL (n = 290, age: median (1st-3rd quartile): 4.8 (3.

Measuring Knowledge of Healthcare Providers on Pediatric Palliative Care with an Online Questionnaire Based on the National Core Curriculum in Italy.

There is a lack of highly reliable tools evaluating healthcare professionals' competences on Pediatric Palliative Care (PPC) and Pain Therapy (PT). The aim of this study is to document the development of an online questionnaire to assess Perceived, Wished and Actual Knowledge of healthcare workers on PPC/PT. The tool was built on the basis of the Italian Society for Palliative Care PPC Core Curriculum (CC) for physicians, nurses and psychologists.

Therapeutic Targeting of ALK in Neuroblastoma: Experience of Italian Precision Medicine in Pediatric Oncology.

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Patients with relapsed/refractory disease have a poor prognosis, and additional therapeutic options are needed. Mutations and amplifications in the (Anaplastic Lymphoma Kinase) gene constitute a key target for treatment.

Case report: Venetoclax therapy in a boy with acute myeloid leukemia in Shwachman Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is a rare bone marrow failure syndrome characterized by exocrine pancreatic insufficiency, bone abnormalities, progressive cytopenia, and predispositions to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). AML, in these patients, is associated with a poor prognosis and with an increased risk of organ toxicity and infectious complications from chemotherapy and hematopoietic stem cell transplantation (HSCT), thus leading to high rates of treatment-related morbidity and mortality. The BCL-2 inhibitor venetoclax has revolutionized the treatment of AML in elderly adults, especially for treatment-naive elderly patients who are ineligible for intensive chemotherapy.

A Validated HPLC-Diode Array Detection Method for Therapeutic Drug Monitoring of Thiopurines in Pediatric Patients: From Bench to Bedside.

Thiopurine drugs are part of the therapeutic armamentarium for pediatric patients suffering from inflammatory bowel disease (IBD) and acute lymphoblastic leukemia (ALL). The therapeutic drug monitoring of these drugs, consisting of measurements of the thiopurine metabolites thioguanine nucleotides (TGN) and methylmercaptopurine nucleotides (MMPN) are used to optimize the effectiveness of treatment and prevent adverse effects. In this context, we developed and validated a high-performance liquid chromatography-diode array detection (HPLC-DAD) method for the simultaneous quantification of thiopurine metabolites according to the most recent International Council for Harmonisation (ICH) guidelines.

Neuroblastic tumors and neurofibromatosis type 1: A retrospective multicenter study in Italy and systematic review of the literature.

Background: Neuroblastic tumors (NBTs) are the most common extra-cranial solid tumors of childhood. Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disorder with a predisposition to tumors. The co-occurrence of NBTs in the setting of NF1 has been occasionally reported, suggesting a non-casual association and likely configuring a spectrum of neural crest-derived disorders.

Rhabdomyosarcoma with unknown primary tumor site: A report from European pediatric Soft tissue sarcoma Study Group (EpSSG).

Background: Rhabdomyosarcoma (RMS) is an aggressive malignancy, and 20% of children present with metastases at diagnosis. Patients presenting with disseminated disease very occasionally have no clear evidence of a primary tumor mass. As these patients have rarely been investigated, we report on a series of patients with RMS and unknown primary tumor site registered in the Metastatic (MTS) RMS 2008 protocol (October 2008 to December 2016) coordinated by the European pediatric Soft tissue sarcoma Study Group.

Cytofluorimetric assay to investigate variability in blinatumomab response.

Background: The T-cell engager antibody blinatumomab (BlincytoT⁢M) represents a promising rescue therapy for relapsed/refractory CD19+ acute lymphoblastic leukemia (B-ALL), although ~20-30% of patients still do not respond to treatment. Blinatumomab creates a tight synapsis between CD3+ T-lymphocytes and leukemic CD19+ B-cells, resulting in a granzyme B (GzB)-mediated specific lysis of leukemic cells.

Methods: Aim of the study was to provide evidence that variability in blinatumomab response could have a genetic basis in , one of the most often mutated genes in B-ALL, affecting the CD19 surface expression on lymphoblasts, and could be explored by means of a cytofluorimetric assay, staining both surface antigens (CD45, CD19 and CD3) and intracytoplasmic markers (7AAD, Syto16).

A Novel ELISA-Based Peptide Biosensor Assay for Screening ABL1 Activity : A Challenge for Precision Therapy in BCR-ABL1 and BCR-ABL1 Like Leukemias.

The pathogenic role of the overactivated ABL1 tyrosine kinase (TK) pathway is well recognized in some forms of like acute lymphoblastic leukemia (ALL); TK inhibitors represent a useful therapeutic choice in these patients who respond poorly to conventional chemotherapy. Here we report a novel peptide biosensor (P)-ELISA assay to investigate ABL1 activity in four immortalized leukemic cell lines with different genetic background. The P sequence comprises an ABL1 tyrosine (Y) phosphorylation site and a targeting sequence that increases the specificity for ABL1; additional peptides (Y-site-mutated (P-) and fully-phosphorylated (P-) biosensors) were included in the assay.