Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) has largely improved the prognosis of leukemia patients. However, relapse is still a major concern. One promising option for the prevention of relapse is vaccination therapy. The post allogeneic HSCT period provides a unique platform for vaccination, because tumor burden is minimal, lymphopenic condition allows for rapid expansion of cytotoxic T cells (CTLs), donor-derived CTLs are not exhausted and inflammatory condition is caused by allo reactions. Tumor cells, dendritic cells and peptides have been used as vaccines targeting leukemia-associated antigens or minor histocompatibility antigens. Clinical trials with several types of vaccines for post-HSCT patients showed that the vaccination induced immunological response and might benefit patients with minimal residual disease, while their effect in patients with advanced disease were limited. To enhance the effect, vaccination in combination with other immune-modulatory drugs such as checkpoint antibodies is now being considered.
Acknowledgements
We wish to thank all staff of the Departments of Hematology and Oncology in Osaka University, Osaka City University and Kyoto University for their outstanding management of the patients. We would also like to thank Dr. Yuji Heike (National Cancer Center of Japan) for the fruitful discussion.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Relapse is a major concern in allogeneic HSCT for leukemia patients.
One promising option to prevent relapse after hematopoietic stem cell transplantation (HSCT) is vaccination to boost the graft-versus-leukemia effect.
The post allogeneic HSCT period provides a unique platform for vaccination because tumor burden is minimal; lymphopenia allows for rapid expansion of antigen-specific cytotoxic T cells; donor-derived antigen-specific cytotoxic T cells are not exhausted and inflammatory conditions are induced by allo reactions.
Tumor cells, dendritic cells and LAA-derived peptides were used for vaccination and were shown to induce T-cell response even in patients who were administered with immunosuppressive drugs.
Some preliminary reports suggest that vaccination therapies may have the potential to prevent relapse after allogeneic HSCT.
Randomized trials will be needed to confirm the effect of vaccines for the prevention of relapse after HSCT.
The effect of vaccination is limited in patients with advanced disease.
To improve the efficacy of vaccination therapy, combination with other types of immunotherapy such as immune checkpoint antibodies should be considered.