Graft-versus-host disease: Therapeutic prospects of improving the long-term post-transplant outcomes

•GVHD developed primarily after transplantation when the donor's immune cells attack the recipient's tissues.•The organs that are mostly affected with GVHD include liver, skin, and gastrointestinal tract.•JAK/STAT pathway is considered a promising target in GVHD due to its role in cytokine signalling, development, and function•Antibodies produced by B cells, reduction in regulatory T cells, and immune tolerance disruption to self-antigen plays a significant role in the disease progression.•JAK inhibitors, monoclonal antibodies, and proteasome inhibitors are widely used for the treatment of GVHD. Graft-versus-host disease (GVHD) continues to emerge as the topmost causative factor of the morbidity and mortality rate post hematopoietic stem cell transplantation. The graft cells attack the recipient host tissues resulting in acute or chronic GVHD that affect organs, including the lung, liver, skin, and gastrointestinal tract. Certain factors are considered to play a crucial role in the progression of the disease, such as antibodies produced by B cells, reduction in regulatory T cells, and immune tolerance disruption to self-antigen. This review highlighted the pathophysiology of GVHD, clinical manifestation, stages of GVHD in different organs, and the significant role played by Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) in cytokine signalling, development, and function of several immune cells. Furthermore, we discussed the clinical efficacy of drugs, which comprises JAK inhibitors, monoclonal antibodies, and proteasome inhibitors that are widely used to treat GVHD. Considering the progress recorded in identifying the therapeutic regimens for GVHD, novel and effective therapeutic approaches are much needed to alleviate the complication that arises post hematopoietic stem cell transplantation and reduce the morbidity and mortality rate of the disease.