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This report describes a pediatric case of isolated agranulocytosis occurring months after hematopoietic stem cell transplantation (HSCT). Secondary cytopenia, or secondary transplant failure, affects 10%–25% of HSCT recipients, with potential triggers including viral infection, graft-versus-host disease (GVHD), sepsis, and certain medications. Viral reactivation was ruled out based on negative PCR results, while GVHD and sepsis were ruled out based on the patient’s clinical presentation. The patient, who received an HLA 10/10 unrelated donor T-cell transplant, underwent standard myeloablative conditioning to minimize the risk of graft rejection. However, agranulocytosis persisted even after discontinuation of myelotoxic drugs such as valganciclovir and ruxolitinib. Further investigation revealed that the patient had been taking febuxostat, which was subsequently discontinued, leading to a recovery of the neutrophil count. The European Medicines Agency lists agranulocytosis as a rare side effect of febuxostat. The effect of candidate genes and variants involved in febuxostat pharmacokinetics and pharmacodynamics was done using the Pharmacogenomics Knowledge Base (PharmGKB) to accurately evaluate an individual’s risk for neutropenia. This case suggests that genetic variants in renal transporters ABCG2 (exonic non-synonymous variant, rs2231137), SLC29A1 (rs747199 and rs628031), and ABCC4 (3′UTR SNP, rs3742106 and rs11568658) may contribute to drug-induced agranulocytosis. This finding underscores the importance of genetic profiling in the management of patients undergoing HSCT to prevent adverse drug reactions.

Optimized use of prophylactic or therapeutic donor lymphocyte infusions (DLI) is aimed at improving clinical outcomes in patients with malignant and non-malignant hematological diseases who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Memory T-lymphocytes (CD45RA−/CD45RO+) play a crucial role in immune reconstitution post-HSCT. The infusion of memory T cells is proven to be safe and effective in improving outcomes due to the enhanced reconstitution of immunity and increased protection against viremia, without exacerbating graft-versus-host disease (GVHD) risks. Studies indicate their persistence and efficacy in combating viral pathogens, suggesting a viable therapeutic avenue for patients. Conversely, using virus-specific T cells for viremia control presents challenges, such as regulatory hurdles, cost, and production time compared to CD45RA-memory T lymphocytes. Additionally, the modulation of regulatory T cells (Tregs) for therapeutic use has become an important area of investigation in GVHD, playing a pivotal role in immune tolerance modulation, potentially mitigating GVHD and reducing pharmacological immunosuppression requirements. Finally, donor T cell-mediated graft-versus-leukemia immune responses hold promise in curbing relapse rates post-HSCT, providing a multifaceted approach to therapeutic intervention in high-risk disease scenarios. This comprehensive review underscores the multifaceted roles of T lymphocytes in HSCT outcomes and identifies avenues for further research and clinical application.

Glycopyrrolate is a competitive muscarinic receptor antagonist used in the treatment of sialorrhea, especially in pediatrics. Degradation research was conducted to better understand the stability of the active pharmaceutical ingredient (API). Using an HPLC-UV method, we evaluated the chemical stability of the oral solution of the galenic compound glycopyrrolate 0.5 mg/mL under different storage conditions. Method validation was performed according to the International Council for Harmonization (ICH) Q2(R2) guidelines. The results of the stability study of the galenic compound in different storage conditions, with the exception of those stored in glass containers at 45 °C for more than 3 months, were stable (100 ± 10% of the nominal concentration). The aim of this work was to study the stability of the galenic compound glycopyrrolate in two different types of containers and at three different storage temperatures. Glycopyrrolate showed degradation beyond the limits only in glass at 45 °C and after 2 months of storage. The results indicate that oral liquid dosage forms of glycopyrrolate are stable for at least 210 days when stored at room temperature or at 4 °C, in glass or PET, for at least 7 months, maintaining product quality according to the standards established by the European Pharmacopoeia, ensuring long-term coverage for pediatric patient therapies.

IntroductionHuman polyomaviruses (HPyVs) cause persistent/latent infections in a large fraction of the population. HPyV infections may cause severe diseases in immunocompromised patients. Malawi polyomavirus (MWPyV) is the 10th discovered human polyomavirus (HPyV 10). MWPyV was found in stool samples of healthy children. So far, the few investigations carried out on HPyV 10 did not find an association with human disease.MethodsIn this study, to verify the putative association between MWPyV and human diseases, MWPyV seroprevalence was investigated in patients affected by i) lymphoproliferative disorders (LPDs) and ii) immune system disorders, i.e., autoimmune diseases (ADs), and in iii) healthy subjects. An indirect ELISA, employing virus-like particles (VLPs) to detect serum IgG antibodies against MWPyV/HPyV 10, was carried out. The study also revealed the prevalence of another polyomavirus, Merkel cell polyomavirus (MCPyV).ResultsSera from patients with distinct autoimmune diseases (n = 44; mean age 20 years) had a prevalence of MWPyV antibodies of 68%, while in patients with lymphoproliferative disorders (n = 15; mean age 14 years), subjected to bone marrow transplantation, the prevalence was 47%. In healthy subjects (n = 66; mean age 13 years), the prevalence of MWPyV antibodies was 67%. Our immunological investigation indicates that MWPyV/HPyV 10 seroconversion occurs early in life and MWPyV/HPyV 10 appears to be another polyomavirus ubiquitous in the human population. A significantly lower MWPyV antibody reactivity together with a lower immunological profile was detected in the sera of LPD patients compared with HS2 (*p < 0.05) (Fisher’s exact test). LPD and AD patients have a similar MCPyV seroprevalence compared with healthy subjects.DiscussionMWPyV seroprevalence indicates that this HPyV is not associated with lymphoproliferative and autoimmune diseases. However, the ability to produce high levels of antibodies against MWPyV appears to be impaired in patients with lymphoproliferative disorders. Immunological investigations indicate that MWPyV seroconversion occurs early in life. MCPyV appears to be a ubiquitous polyomavirus, like other HPyVs, in the human population.