Respiratory viral infections are known causes of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Here, we report a unique case of a child with viral pneumonia caused by coinfection with human metapneumovirus (MPV), respiratory syncytial virus (RSV), and SARS‐CoV‐2 after HSCT. A 9‐year‐old girl with acute lymphoblastic leukemia underwent allogeneic HSCT from a matched, unrelated donor. During the post‐transplant period, in profound leukopenia (below 10 leukocytes/µL), she was diagnosed with SARS‐CoV‐2, MPV, and RSV pneumonia and was treated with ribavirin and chloroquine. Before leukocyte recovery, the girl became asymptomatic, and SARS‐CoV‐2 and RSV clearance was achieved. The shedding of SARS‐CoV‐2 stopped before immune system recovery, and one may hypothesize that the lack of an inflammatory response might have been a contributing factor to the mild clinical course. Post‐transplant care in HSCT recipients with COVID‐19 infection is feasible in regular transplant units, provided the patient does not present with respiratory failure. Early and repeated testing for SARS‐CoV‐2 in post‐transplant patients with concomitant infection mitigation strategies should be considered in children after HSCT who develop fever, respiratory symptoms, and perhaps gastrointestinal symptoms to control the spread of COVID‐19 both in patients and in healthcare workers in hospital environments. Training of staff and the availability of personal protective equipment are crucial for containing SARS‐CoV‐2 infection.

Severe aplastic anemia (SAA) is a bone marrow failure syndrome that can be treated with hematopoietic cell transplantation (HCT) or immunosuppressive (IS) therapy. A retrospective cohort of 56 children with SAA undergoing transplantation with fludarabine–cyclophosphamide–ATG-based conditioning (FluCyATG) was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GVHD) and CI of viral replication. Engraftment was achieved in 53/56 patients, and four patients died (two due to fungal infection, and two of neuroinfection). The median time to neutrophil engraftment was 14 days and to platelet engraftment was 16 days, and median donor chimerism was above 98%. The overall incidence of acute GVHD was 41.5%, and that of grade III-IV acute GVHD was 14.3%. Chronic GVHD was diagnosed in 14.2% of children. The probability of 2-year GVHD-free survival was 76.1%. In the univariate analysis, a higher dose of cyclophosphamide and previous IS therapy were significant risk factors for worse overall survival. Episodes of viral replication occurred in 33/56 (58.9%) patients, but did not influence OS. The main advantages of FluCyATG include early engraftment with a very high level of donor chimerism, high overall survival and a low risk of viral replication after HCT.

CD19-targeted CAR-T cell therapy has revolutionized the treatment of relapsed/refractory (r/r) pre-B acute lymphoblastic leukemia (ALL). However, it can be associated with acute toxicities related to immune activation, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokines released from activated immune cells play a key role in their pathophysiology. This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel. Serial measurements of C-reactive protein, fibrinogen, ferritin, IL-6, IL-8, IL-10, IFNγ, and TNFα were taken before treatment and on consecutive days after infusion. The incidence of CRS was 77.8%, and the incidence of ICANS was 11.1%. No CRS of grade ≥ 3 was observed. All complications occurred within 14 days following infusion. Higher biomarker concentrations were found in children with CRS grade ≥ 2. Their levels were correlated with disease burden and CAR-T cell dose. While cytokine release syndrome was common, most cases were mild, primarily due to low disease burden before lymphodepleting chemotherapy (LDC). ICANS occurred less frequently but exhibited various clinical courses. None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure.

Background/Objectives: The objective of this study was to analyze the clinical and laboratory features, management, outcomes, and complications of PRES in children with malignancies or following hematopoietic cell transplantation (HCT). Methods: This was a multicenter retrospective analysis of PRES episodes diagnosed between 2014 and 2022 in Polish pediatric hematology and oncology (PHO) centers and HCT units. The study included 438 patients treated for malignancy or post-HCT: 120 with PRES (study group) and 318 without PRES (control group). Results: PRES was diagnosed in children aged 1.7–16.5 years (median = 7.7 years). The most common underlying diagnosis was ALL (76.7%; n = 92). Symptoms of PRES included disturbances of consciousness (84.2%), seizures (80.0%), hypertension (74.2%), apathy (64.2%), abdominal pain (45.0%), visual disturbances (28.3%), and headaches (26.7%). Electrolyte abnormalities were observed in 75.0% of children, most commonly hyponatremia (49.2%) and hypokalemia (37.5%). Children with PRES were more likely to require admission to the intensive care unit (ICU) than controls (50.0% vs. 29.6%, p < 0.001). The most frequent long-term complications of PRES were hypertension (22.5%) and epilepsy (20.8%). Among PHO patients, those with PRES had significantly lower DFS (76.7% vs. 93.7%, p < 0.001) and OS (79.2% vs. 93.4%, p < 0.001). In the HCT group, PRES was also associated with lower DFS (40.0% vs. 83.3%, p = 0.012) and OS (40.0% vs. 77.8%, p = 0.047). Conclusions: PRES is a significant complication of oncological and transplant treatment in children. Its occurrence was associated with worse overall and disease-free survival. We proposed a predictive index for PRES, diagnostic criteria, and a revised name for this syndrome.