Ayako Yamamori

Reticular dysgenesis (RD) is characterized by severe combined immunodeficiency and agranulocytosis with hematopoietic stem cell transplantation (HSCT) being the only curative therapy. Severe neutropenia in RD is typically unresponsive to recombinant human granulocyte colony-stimulating factor (rhG-CSF). To delineate lineage-specific transcriptional responses and cellular heterogeneity induced by rhG-CSF, we integrated single-cell RNA sequencing from seven samples, including two RD patients (with and without rhG-CSF) and three pediatric controls. We identified a moderate increase in hematopoietic stem and progenitor cells (HSPCs) and common myeloid progenitor/granulocyte–monocyte progenitor fractions following rhG-CSF. Notably, B cell fractions increased after rhG-CSF, accompanied by enhanced maturation from common lymphoid progenitors to precursor B cells. In parallel, genes involved in B cell differentiation were markedly upregulated compared with untreated cells. It also modulated the HSPC compartment by markedly suppressing interferon-γ (IFNγ) signaling pathways. RhG-CSF administration before HSCT may benefit patients with RD by modestly increasing neutrophils and supporting infection control, while suppressing IFNγ signaling in HSPCs and potentially promoting B cell differentiation.

Allogeneic hematopoietic cell transplantation (HCT) is a crucial treatment for various diseases, including hematological malignancies, solid tumors, and genetic disorders. Despite its curative potential, HCT is associated with severe complications, notably infections, graft-versus-host disease, and organ damage. Infections, particularly bloodstream infections (BSIs), pose a significant threat in the initial weeks post-HCT, necessitating effective management strategies. This retrospective study aimed to clarify the incidence, pathogens, and risk factors associated with BSI within the first 30 days after allogeneic HCT in children/adolescents and young adults (AYAs). The study included 115 patients aged Streptococcus mitis/oralis being the most common. In multivariable analysis, tandem HCT (subdistribution hazard ratio [SHR]: 5.67, 95% CI: 2.74–11.7, p < 0.001) and peripherally inserted central catheters (SHR: 2.96, 95% CI: 1.34–6.55, p = 0.007) were identified as independent risk factors for BSI. In patients receiving tandem HCT, the pathogens isolated from blood cultures were all gram-positive bacteria, with Streptococcus mitis/oralis accounting for up to 67% of the isolated pathogens. Tandem HCT and PICCs were identified as independent risk factors for BSI after allogeneic HCT in children/AYAs. The pathogens were commonly gram-positive, and Streptococcus mitis/oralis is important in patients who received tandem HCT. These data can provide valuable information for future studies to consider effective interventions to reduce the risk of BSI in high-risk patients.