ABSTRACTBackgroundLittle is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer.MethodsWe collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) 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).ResultsThe 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.ConclusionsSARS-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 the 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.
About two-thirds of pediatric patients with PP-IFI survived, regardless of whether the infection occurred after frontline chemotherapy, reinduction chemotherapy for disease relapse, or after HSCT. Further prospective studies are needed to define the impact of antifungal prophylaxis and early combination therapy on short-term overall survival.
Purpose
Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2.
Methods
We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS).
Results
Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2–28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5–16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT.
Conclusion
HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency.
Clinical Implications
HCT is a definitive cure for DADA2 with > 95% survival.
Bloodstream infections (BSIs) after chemotherapy or hematopoietic stem cell transplantation (HSCT) are a leading cause of morbidity and mortality. Data on 154 BSIs that occurred in 111 onco-hematological patients (57 hematological malignancies, 28 solid tumors, and 26 non-malignant hematological diseases) were retrospectively collected and analyzed. Monomicrobial Gram-positive (GP), Gram-negative (GN), and fungal BSIs accounted for 50% (77/154), 38.3% (59/144), and 3.2% (5/154) of all episodes. Polymicrobial infections were 7.8% (12/154), while mixed bacterial–fungal infections were 0.6% (1/154). The most frequent GN isolates were Escherichia coli (46.9%), followed by Pseudomonas aeruginosa (21.9%), Klebsiella species (18.8%), and Enterobacter species (6.3%). Overall, 18.8% (12/64) of GN organisms were multidrug-resistant (seven Escherichia coli, three Klebsiella pneumoniae, and two Enterobacter cloacae), whereas GP resistance to glycopeptides was observed in 1% (1/97). Initial empirical antibiotic therapy was deemed inappropriate in 12.3% of BSIs (19/154). The 30-day mortality was 7.1% (11/154), while the bacteremia-attributable mortality was 3.9% (6/154). In multivariate analysis, septic shock was significantly associated with 30-day mortality (p = 0.0001). Attentive analysis of epidemiology and continuous microbiological surveillance are essential for the appropriate treatment of bacterial infections in pediatric onco-hematological patients.
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