SARS-CoV-2 Infection in the Pediatric Oncology Population: The Definitive Comprehensive Report of the Infectious Diseases Working Group of AIEOP.

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.

Abdominal rhabdoid tumor presenting with symptomatic spinal epidural compression in a newborn. A case report.

The occurrence of an abdominal tumor invading the spinal canal and causing symptoms of epidural compression is rare in an infant, and exceptional at birth. Peripheral neuroblastic tumors are by far the most common cause. Emergency chemotherapy is commonly curative, though permanent sequelae are possible. Although other malignancies may be involved, no case of rhabdoid tumors at birth has been reported. We describe the case of a neonate who presented symptoms of spinal epidural compression at birth secondary to a rhabdoid tumor. As expected with this highly malignant tumor, the patient experienced a rapidly progressive clinical course and died within three months of diagnosis.

Favorable outcome of SARS-CoV-2 infection in pediatric hematology oncology patients during the second and third pandemic waves in Italy: a multicenter analysis from the Infectious Diseases Working Group of the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP).

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.

Bilateral adrenal primary tumor in Stage 4S neuroblastoma: The Italian experience and review of the literature.

Bilateral adrenal neuroblastoma (NB) is rare and is mainly stage 4S. Its incidence, presenting features, management, and outcome have not been fully defined yet. We searched the Italian NB Registry (RINB) for stage 4S NB infants with bilateral adrenal primary tumor to compare them with stage 4S NB with unilateral tumor. Between 1979 and 2016, the RINB enrolled 3731 NB patients aged 0-18 years including 317 infants (8.5%) diagnosed with stage 4S NB. Eleven/317 (3.5%) had a bilateral adrenal primary tumor (Group 1) and 190/317 (59.9%) had a unilateral tumor (Group 2). Group 1 infants were significantly younger (51 vs. 89 days) but were comparable with Group 2 for any other presenting features. In the absence of specific protocols, upfront treatment was based on symptoms, size of adrenal tumors, and biology, and consisted of observation in 5 cases, radiotherapy in one, chemotherapy in 2, and surgery in 3. Five/11 developed progression and 2 of them, both with MYCN amplification, died. The 5-year EFS rates of Group 1 and 2 were 54.5% vs. 73.3% (P=.14) and 5-year OSs were 81.8% and 89.4%, respectively (P=.44). Our data support the hypothesis that 4S NB infants with bilateral adrenal tumors can have favorable outcome with personalized therapeutic approach. The three patients with MYCN amplified tumor benefited from upfront aggressive chemotherapy, in accordance with current protocols. Because of the rarity of this intriguing form of neuroblastoma, collaborative prospective studies are warranted, especially in view of gaining a better insight on its biological and genetic features.

Case Report: Deficiency of Adenosine Deaminase 2 Presenting With Overlapping Features of Autoimmune Lymphoproliferative Syndrome and Bone Marrow Failure.

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disease associated with a highly variable clinical presentation, such as vasculitis, inflammation, and hematologic manifestations. Some associations of clinical features can mimic autoimmune lymphoproliferative syndrome (ALPS). We report a case of a female patient who fulfilled the 2009 National Institute of Health revised criteria for ALPS and received a delayed diagnosis of DADA2. During her childhood, she suffered from autoimmune hemolytic anemia, immune thrombocytopenia, and chronic lymphoproliferation, which partially responded to multiple lines of treatments and were followed, at 25 years of age, by pulmonary embolism, septic shock, and bone marrow failure with myelodysplastic evolution. The patient died from the progression of pulmonary disease and multiorgan failure. Two previously unreported variants of gene ADA2/CECR1 were found through next-generation sequencing analysis, and a pathogenic role was demonstrated through a functional study. A single somatic STAT3 mutation was also found. Clinical phenotypes encompassing immune dysregulation and marrow failure should be evaluated at the early stage of diagnostic work-up with an extended molecular evaluation. A correct genetic diagnosis may lead to a precision medicine approach consisting of the use of targeted treatments or early hematopoietic stem cell transplantation.