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Background and Objective: The Hyper-CVAD/Methotrexate-Cytarabine (H-CVAD/MTX-AraC) chemotherapy protocol has been one of the standard treatments for blood cancers, such as Mantle cell lymphoma (MCL), Burkitt's lymphoma (BL) and B-cell and T-cell acute lymphoblastic leukaemia (ALL). Due to high toxicity, it has been progressively replaced with new specific regimens with a better safety profile (GELA protocol for MCL, BURKIMAB for BL and PETHEMA for B-cell and T-cell ALL). The objective of this study is to analyse the toxicity and infectious complications of these therapeutic regimens, as well as the event free survival (EFS)., Patients and Methods: This is a retrospective and descriptive observational study of 81 patients, comparing 42 patients treated with H-CVAD/MTX-AraC (group A) versus 39 patients treated with GELA/BURKIMAB/PETHEMA (group B)., Results: All patients in group A developed pancytopenia, but in group B 74.4% neutropenia, 51.3% thrombocytopenia and 69.2% anaemia. The total number of infections in group A was higher than in group B: 154 versus 48, 3.67 versus 1.23 per patient and 0.59 versus 0.25 per cycle. Likewise, febrile neutropenia happened: 106 versus 21 cases, 2.52 versus 0.52 per patient and 0.41 versus 0.11 per cycle. EVS is higher in group B: 33% versus 79% (2-year), and 24% versus 69% (5-year)., Conclusions: Current therapeutic protocols have shown higher EFS due to better safety profile, with less haematological, neurological and haemorrhagic toxicity, as well as lower rates of infectious complications., Competing Interests: The authors declare that they have no conflict of interest., (© the authors; licensee ecancermedicalscience.)