The treatment of patients with malignant blood cells is a complex and lengthy process that lasts several months or sometimes years with persistent relapses of the disease. In this paper, the focus will be on B-cell lymphomas and acute myeloid leukemia associated with therapy for the purpose of case presentation. High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ATKMS) is an established therapy in the treatment of patients with Non-Hodgkin's lymphoma (NHL) in whom conventional therapy has failed. With the improvement of the supportive care measure, the mortality rate in transplantation has been reduced to <5% and the life expectancy of patients is being extended. Since the early 1990s, however, several studies have documented an increased risk of secondary malignancies including myelodysplastic syndrome and acute myeloid leukemia. The prognosis of patients with t-AML /t-MDS is generally poor, even with aggressive chemotherapy. Exposure to chemotherapy and an increased risk of developing secondary MDS / AML have been documented in many studies. Acute therapy-related acute myeloid leukemia is described in the WHO classification as AML, which occurs after previous cancer whose treatment mainly includes an alkalizing agent and ionizing radiation therapy leading to chromosome 5 or 7 abnormalities. Poor prognosis of t-AML was observed for the first time in patients with multiple myeloma treated with melphalan. Thereafter, almost all other alkalizing agents are associated with an increased risk of t-AML in patients treated for a wide range of diseases. The individualization of this category of AML has made it possible to highlight the different biological and clinical features of this entity, which is typically characterized by a poor outcome. Although most of the knowledge about the relationship between previous exposure to cancer therapy and therapy-related AML comes from epidemiological studies, there are arguments for a direct impact of cytotoxic therapy on leukemogenesis. More recently, cytotoxic therapy has been shown to favor the proliferation of rare hematopoietic stem cells carrying TP53 mutations in the founder clone that primarily spread after therapy and evolve to leukemia through the collection of chromosomal abnormalities typically found in t-AML.