Background: Leukemia in children has a good prognosis with an overall cure rate of 85% in pediatric patients with acute lymphoblastic leukemia and 50-60% in pediatric patients with acute myeloid leukemia. Nevertheless in patients with refractory or relapsed leukemia the prognosis is limited and can only be cured by a salvage chemotherapy, in most cases followed by an allogeneic hematopoietic stem cell transplantation. Methods: In this retrospective case cohort ananlysis we investigated the outcome of eight patients with relapsed or refractory acute myeloid (n=2), lymphoblastic (n=4), biphenotypic (n=1) leukemia or T-lymphoblastic lymphoma (n=1) who failed to respond to standard salvage regimens. They received a salvage therapy with melphalan and cytarabine at our institution between 2015 and 2019. Results: After salvage chemotherapy with melphalan and cytarabine 63% of the patients achieved a remission of the disease and qualified for subsequent allogeneic hematopoietic stem cell transplantation. The one year overall survival rate was 50%, the three year overall survival rate was 29%. 25% of patients experienced a temporary period of fever and SIRS. Conclusions: The reported results of our case cohort analysis indicate that a salvage therapy with melphalan and cytarabine in relapsed or refractory leukemia could represent a curative approach with the possibility of achieving remission and subsequent allogeneic hematopoietic stem cell transplantation. Future multicentre studies are needed to verify the here presented results.