Over the past century, the medical community has developed a fundamental understanding of leukemia and recognized the importance of basing the classification on multiple features of malignant cells based on morphological, cytogenetic, molecular biological and immunological markers. At the beginning of the 21st century, we excitedly foresee that leukemia, a large group of diseases, will be eradicated one by one. This is not only a boon for leukemia patients, but also provides a paradigm for the eradication of other malignancies. The following is a review of important therapeutic advances in leukemia and a brief overview of the current status and dynamics of its treatment. I. Drugs for leukemia After the introduction of cytarabine, anthracyclines and anthraquinones in the 1960s, the efficacy of ALL and acute myeloid leukemia (AML) has been further improved. The long-term efficacy of drugs for AML in children and adults, with the exception of acute promyelocytic leukemia (APL), is far from satisfactory. Prof. Zhen-Yi Wang et al. demonstrated a high remission rate of all-trans retinoic acid in APL. Although the eradication rate with this drug alone is still very low, it is certainly a milestone in the treatment of APL. The application of arsenic trioxide and the application of purified arsenic trisulfide and tetraarsenic tetrasulfide oral formulations have achieved high efficacy in the treatment of APL, with the latter having better long-term remission rates than allogeneic and autologous bone marrow transplantation, with an expected 5-year survival rate of more than 90% and being the most curable type of leukemia available, with cytogenetics and molecular biology having important relevance for classification and treatment. The importance of this specific therapeutic principle is also confirmed by the superior efficacy of tyrosine kinase inhibitors (e.g., STI-571) in the treatment of bcr/abl-positive t(9;22) CML. Both arsenic sulfide and STI-571 are characterized by low toxicity and high efficacy. It is expected that other leukemias and malignancies will also find specific treatments based on cell biology. Over the past 20 years, the medical community has increasingly recognized that the central nervous system and the testis, where drug concentrations are low, are a refuge for residual leukemic lesions. Increased doses of MTX, intrathecal administration and radiation therapy of the CNS have also received attention. In addition, due to the discovery of levomucoidase, which is effective not only for leukemic cells but also for CNS leukemia, its routine application in ALL has greatly improved the cure rate of ALL by drug therapy. The success of SCT is one of the few most exciting medical advances since the 1950s. Through SCT, at least 60 previously incurable diseases have been cured. The value of SCT has been universally accepted since 1971, when Thomas et al. first reported that SCT could lead to long-term survival of leukemia patients. Thomas also became the first clinician to receive the Nobel Prize. In terms of the source of hematopoietic stem cells, allogeneic SCT is still represented by bone marrow transplantation. Most bone marrow is still harvested from siblings, but non-related bone marrow or other sources of stem cells have accounted for more than 1/3 of SCT worldwide. In addition, hematologists have found that peripheral blood also contains hematopoietic stem cells. After receiving granulocyte or granulocyte monocyte colony-stimulating factor (G-CSF, GM-CSF), hematopoietic stem cells from the bone marrow are mobilized into the peripheral blood. Therefore, it is also possible to replace the bone marrow with single nucleated cells (which contain hematopoietic stem/progenitor cells) concentrated in the peripheral blood of the donor for the purpose of reconstituting the bone marrow and immune function. In addition, studies over the last decade have demonstrated that placental/umbilical cord blood (PCB) is rich in hematopoietic stem/progenitor cells and can be used as an important source of hematopoietic stem cells, especially for unrelated hematopoietic stem cells. The most threatening comorbidities of transplantation therapy are graft-versus-host disease (GVHD) and infection. Improvements in anti-GVHD measures have also significantly reduced the morbidity and mortality of SCT. This is due to the use of various immunosuppressive agents, such as MTX, cyclosporine A, FK506, mycophemolate mofetile (MMF) and glucocorticoids, as well as the increasingly sophisticated techniques for removing T lymphocytes from the bone marrow. Immunotherapy The SCT described above is actually a combination of mega-dose chemotherapy/radiotherapy and effective inherited immunotherapy. Chronic GVHD is closely related to graft-versus-leukemia effect (GVL). Moreover, when leukemia relapses after SCT, lymphocyte infusion from the donor has a definite efficacy. These facts play an important encouraging role for immunotherapy of malignancies. In addition to cellular immunity, interleukin 2, gamma interferon and new varieties of interferon have been used successively as immunotherapy for leukemia. Studies have shown that fusion gene products formed by gene translocations in leukemia cells have a role in tumor immune rejection of antigens, and vaccine therapy using fusion genes or gene products is also under active investigation, with some already in clinical trials. Anti-CD33 monoclonal antibody has been used to treat acute myeloid leukemia with certain efficacy. Gene therapy As leukemia is gradually recognized as a class of diseases with genetic abnormalities, gene therapy may, in principle, become a highly specific means of treating leukemia. However, other applications of gene transfer for the treatment of leukemia have been developed and are more feasible, despite the following difficulties: inefficiency of the vector, low specificity for the target cells, and the scattered nature of leukemic cells. The use of marker genes can provide more accurate information about the cellular kinetics of leukemia patients after they have received immunotherapy. Marker genes can also provide information on the presence, expansion and activity of infused antiviral and tumor cells (CTLS) in vivo. The “suicide base? The most common method of gene therapy for leukemia is the introduction of immunomodulatory genes into a small subset of leukemic cells. These highly immunogenic leukemic cells will excite numerous untransfected leukemic cells in other parts of the body that express the same leukemia-specific associated antigens to produce an anti-leukemic effect. This approach is being tried in patients with chronic lymphocytic leukemia, CML, AML and ALL using genes encoding certain cytokines, lymphokines and co-stimulatory molecules. In summary, leukemia has been partially cured. In the twenty-first century, hematologists are preparing new efforts to achieve the goal of being able to eradicate the vast majority of leukemias.