Immunotherapy of refractory and relapsed acute lymphoblastic leukemia in childhood and adolescence

Acute lymphoblastic leukemia (ALL) represents the most frequent malignant disease in childhood and adolescence and offers a good prognosis with approximately 80% survival in first remission after polychemotherapy and radiotherapy. In addition, many children with relapsed or refractory ALL will still be cured by allogeneic hematopoietic stem cell transplantation (alloHSCT). However, therapeutic options are limited with a very poor prognosis in case of another relapse after alloHSCT. Here, immunotherapy strategies offer a promising alternative to another chemotherapy or second alloHSCT, which are mainly palliative and accompanied by high morbidity and mortality. Immunotherapy strategies aim at an improvement of the graft-versus-leukemia (GvL) effect. The therapeutic GvL effect is usually associated with graft-versus-host disease (GvHD). The definition of patients subgroups with an increased risk for relapse after alloHSCT gains growing importance for immunotherapy strategies. Promising approaches for separation of GvL-effect and GvHD after donor lymphocyte infusions, e.g. T-cell suicide gene therapy, will be described. Finally, vaccination strategies for ALL exist.