Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that is mediated by pro-inflammatory cytokines, like interleukin-6 (IL-6). IL-6 plays an important role in synovial inflammation and joint degradation. In this study, a combined in silico, in vitro and in vivo approach was used to identify and preliminarily evaluate valganciclovir hydrochloride as potential modulator of IL-6 receptor mediated inflammatory signalling. Docking studies showed that valganciclovir hydrochloride had favourable binding affinity with IL-6 receptor, and interacted stably with active site. ADMET analysis showed that compound possessed desirable ADMET properties, with good absorption and distribution, and low toxicity. Molecular binding free energy indicated stability of the protein-ligand complex. Moreover, 100 ns molecular dynamics simulation showed stable RMSD, with consistent key interactions, suggesting a dynamically stable protein-ligand complex in the physiological environment. Binding assay further demonstrated concentration dependent inhibition of IL-6:IL-6R interaction. Furthermore, in vivo assessment in collagen induced arthritis rats showed that treatment with valganciclovir hydrochloride resulted in marked reduction in disease severity. The treatment groups demonstrated a decrease in paw swelling, ESR, CRP, RF and IL-6 expression. Treatment also reduced downstream inflammatory mediators such as IL-17, MMP-9, p-STAT3, STAT3 and JAK2, suggesting attenuation of IL-6 associated inflammatory signalling In addition, antioxidant enzyme levels were restored with reduction in lipid peroxidation. The results indicate that valganciclovir hydrochloride has favourable binding interactions, and pharmacokinetics, as well as strong anti-inflammatory and anti-arthritic potential. The combined computational and experimental results support the possible involvement of IL-6/JAK2/STAT3 associated signalling pathways in observed anti-arthritic effects of valganciclovir hydrochloride.

Managing cytomegalovirus (CMV) infection in the post-transplant setting is frequently complicated by severe adverse effects from standard antiviral therapy or viral resistance. We report the cases of two critically ill liver transplant recipients in whom maribavir, a kinase inhibitor approved for refractory/resistant CMV, was used. In the first case, maribavir achieved rapid viral suppression in a 30-year-old patient with refractory CMV infection. In the second case, it served as effective salvage therapy, enabling bone marrow recovery following valganciclovir-induced toxicity while maintaining viral control.  Although both patients ultimately succumbed to non-CMV-related ICU complications, maribavir demonstrated clinical utility in achieving virological control, providing a crucial alternative for complex cases where conventional options are limited.

Secondary graft failure after initial donor engraftment is a rare complication of allogeneic hematopoietic stem cell transplantation (HSCT). We report a 47-year-old man with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (B-ALL) who underwent haploidentical sibling peripheral blood HSCT after second complete remission. Neutrophil engraftment occurred by Day +14 with platelet engraftment by Day +18. Beginning Day +22, recurrent fever with progressive cytopenias developed. Day +30 peripheral blood short tandem repeat (STR) analysis showed complete donor chimerism; however, cytomegalovirus (CMV) DNAemia increased to 3,736 IU/mL, prompting therapeutic valganciclovir. Bone marrow biopsy on Day +37 showed hypocellular marrow without residual disease, although bone marrow X/Y fluorescence in situ hybridization (FISH) demonstrated 100% XY signals despite a female donor, indicating graft loss. Septic shock developed on Day +48. Management included growth factors, temporary tacrolimus withdrawal, antibiotics, granulocyte infusions, and a stem cell boost on Day +62. Repeat peripheral blood chimerism by Day +95 showed complete recipient genotype, confirming secondary graft failure with autologous reconstitution. Follow-up through Day +183 confirmed sustained autologous hematopoiesis with no relapse or graft-versus-host disease (GVHD). This case highlights an uncommon transition from donor-type marrow failure to autologous recovery and underscores the importance of bone marrow-based chimerism monitoring in cytopenic post-transplant patients.

Background/Objectives: Cytomegalovirus (CMV) reactivation is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Letermovir is used to prevent infections, but it is not available in many countries. Ganciclovir and valganciclovir carry a risk of bone marrow suppression. Foscarnet is frequently used as a bone marrow-sparing alternative; however, its clinical utility is constrained by nephrotoxicity. In this study, we aimed to evaluate the efficacy and renal safety of foscarnet and to identify factors associated with acute kidney injury (AKI) occurring during foscarnet treatment. Methods: This real-world, retrospective, single-center cohort study included 40 adult allo-HCT recipients treated with foscarnet for CMV reactivation between May 2022 and February 2025. Results: CMV polymerase chain reaction (PCR) negativity was achieved in 90% of patients, with a median time to PCR negativity of 10 (4-28) days. AKI occurred in 42.5% of patients, and 12.5% required hemodialysis. Foscarnet treatment was associated with a significant increase in serum creatinine levels and significant reductions in potassium, calcium, and magnesium concentrations (p < 0.05 for all). In univariable logistic regression analysis, myeloablative conditioning was associated with higher odds of AKI (OR 10.29, 95% CI 1.15-91.63; p = 0.037), while male sex showed numerically higher odds that did not reach conventional statistical significance (OR 4.28, 95% CI 0.96-19.01; p = 0.056). Conclusions: Among allo-HCT recipients treated with foscarnet, virological clearance was frequently observed, while AKI and electrolyte disturbances were common. These findings suggest that close renal and electrolyte monitoring may be warranted. However, given the retrospective, single-center design, small sample size, and absence of a comparator group, the findings should be interpreted cautiously and confirmed in larger prospective comparative studies.