Background: More than 85% of children affected by acute lymphoblastic leukemia
(ALL) are successfully treated; however relapse remains a remarkable clinical concern, with
50-60% of relapsing patients facing a fatal outcome. Management of relapsed patients includes
standardized intensive risk-adapted regimens based on conventional drugs, and hematopoietic
stem cells transplantation for patients with unfavourable features. Biological drugs,
in particular the monoclonal antibody epratuzumab and the bi-functional recombinant single
chain peptide blinatumomab, have been recently recognized as novel potential agents to be
integrated in salvage ALL therapy to further improve rescue outcome.
Methods: A systematic search of peer-reviewed scientific literature and clinical trials in public
databases has been carried out. Both clinical and pre-clinical studies have been included to
summarize recent evidence on epratuzumab and blinatumomab for salvage ALL therapy.
Results: Sixty-two papers and 25 clinical trials were included. Although not all patients responded
properly to these agents, their use in relapsed and refractory pediatric ALL seems
Conclusion: Phase 3 studies have recently begun and more consistent results about epratuzumab
and blinatumomab safety and efficacy in comparison to conventional therapies are expected
in the next years. Epratuzumab seems safe in the dosing scheme proposed in ALL, but
its efficacy over the conventional chemotherapy is still questionable. Blinatumomab has
shown promising results in high risk cases such as elder adult patients and conclusive studies
on pediatric ALL are needed. Patient inter-individual variability to these agents has not been
investigated in depth, but this issue needs to be addressed, in particular for blinatumomab.