Abstract:
Introduction. Hematopoietic stem cell transplantation (HSCT) represents a life-saving therapy for
hematological malignancies, but its efficacy is often compromised by graft-versus-host disease
(GVHD). GVHD remains a major challenge, as it results from an alloreactive immune response
mediated by donor-derived T cells. The janus kinase (JAK-STAT) pathway plays a critical role in
immune cell activation, cytokine signaling, and the development of GVHD. This study aims to explore
the potential of selective JAK inhibitors in alleviating GVHD, improving transplantation outcomes and
balancing immune suppression with graft-versus-leukemia (GVL) effects.
Materials and Methods. The scientific articles ranging from 2017-2025 published in PubMed, NCBI,
BioMed Central databases, describing the preclinical and clinical studies on JAK inhibitors in HSCT,
the biochemical mechanisms and physiological effects in evaluating the efficacy of ruxolitinib and
itacitinib.
Results. JAK inhibitors have demonstrated efficacy in both preclinical and clinical settings by
reducing T-cell activation, suppressing inflammatory cytokines, and enhancing regulatory T-cell
expansion. In trials, ruxolitinib a JAK1/2 inhibitor, has shown significant improvements in steroidrefractory GVHD, with increased response rates and prolonged survival. Itacitinib, a selective JAK1
inhibitor, has demonstrated a favorable safety profile while preserving GVL effects. Emerging data
suggest that post-transplant combining of JAK inhibitors and cytostatics, such as cyclophosphamide
or other immunomodulatory strategies may further optimize transplant outcomes.
Conclusions. Selective JAK inhibition represents a new area of treatment, offering a targeted approach
to immune modulation while maintaining the beneficial aspects of HSCT. In recent years, selective
JAK inhibitors have emerged as promising alternatives for modulating immune responses, reducing
GVHD severity, and improving transplantation outcomes. Future research is focused on refining
dosing strategies, minimizing side effects and exploring combination therapies to enhance transplant
tolerance. With ongoing clinical trials and advancements, JAK inhibitors have the potential to redefine
post-HSCT immunosuppression, improving both survival and quality of life for transplant recipients.
