Approaches to relapse after allogeneic stem cell transplantation

Relapse has become the leading cause of death following allogeneic hematopoietic stem cell transplantation (HSCT). Despite improved understanding of the biology that underlies the graft-versus-leukemia/tumor effect the relapse rate did not decrease over the past 20 years. In general, prognosis is poor for patients who relapsed to an allograft since effective treatment options are limited. Here, we review the available and upcoming treatment approaches for relapse.

Treatment of relapse after allogeneic HSCT has been rarely investigated systematically and results differ substantially from diseases. Withdrawal of immunosuppressive medication, donor lymphocyte infusions with or without chemotherapy and/or second allogeneic HSCT are the most used options. New specific cellular approaches such as disease-specific T-cells, alloreactive natural killer cells or vaccination strategies are under investigation. Novel agents such as tyrosine-kinase inhibitors, hypomethylating agents, monoclonal antibodies, immunomodulating drugs, or proteasome-inhibitors either alone or in combination with adoptive immunotherapy are upcoming promising options, but valid data are lacking so far.

With some exceptions (chronic myeloid leukemia), treatment options for patients who relapse are limited. The results are poor and the majority of patients ultimately die of their disease. More effort and research is needed to prevent and treat relapse after allogeneic HSCT.