Stem cell transplantation without chemotherapy is expected to achieve safer leukemia treatment

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17ff5fecc9e54c7 - Stem cell transplantation without chemotherapy is expected to achieve safer leukemia treatment

leukemia and other blood cancers usually start in the bone marrow, and the blood cells in the bone marrow are produced by stem cells. For those life-threatening diseases, there is a treatment that can be very effective, but there is a risk of serious side effects – hematopoietic stem cell transplantation (HSCT)

in order to prepare their bodies for donated stem cells, patients first receive radiotherapy or chemotherapy, which will kill their own stem cells, destroy the remaining cancer cells, and weaken their immune system to prevent rejection. This increases the opportunity for new stem cells, which can functionally cure some patients. But it also puts them at high risk of infection, or a dangerous condition called graft-versus-host disease, in which immune cells implanted in tissue attack the patient’s own cells

in the new study, researchers developed a technology that does not require radiation or chemotherapy. Instead, stem cells in bone marrow are more precisely targeted for destruction, using molecules called antibody drug coupling agents (ADCs). These molecules bind to specific proteins on the surface of hematopoietic stem cells, which the team says makes them harmless to other cells. Once they reach their target, ADCs release a drug called saporin to kill stem cells

immunosuppressive drugs are still needed to prevent rejection after donor stem cell transplantation. In this case, the team used a drug called baricitinib, which is currently used to treat rheumatoid arthritis

Stem cell transplantation without chemotherapy is expected to achieve safer leukemia treatment

in the test of leukemia mouse model, this technology led to the success of stem cell transplantation. The combination of ADCs and baricitinib prevented the immune cells of test animals from attacking new stem cells, and they did not appear graft-versus-host disease due to the action of immunosuppressants. During the whole treatment process, the treated mice also maintained a normal number of blood cells, avoiding another common side effect of the existing transplantation methods. The key difference is that radiation or chemotherapy can kill all stem cells at once, while new technologies can replace them more slowly, the team said

importantly, slow treatment means that immunosuppressants can be reduced over time. After the donated stem cells completely replace the patient’s own stem cells, they are not needed at all

the team said that with more work in animal research and final human trials, this treatment method can one day be applied to patients with leukemia and other blood cancer, as well as other diseases that are considered to be too extreme

John dipersio, senior author of the study, said: “It will be a change to be able to carry out stem cell transplantation without radiotherapy or chemotherapy. It can eliminate dangerous low blood cell count, bleeding complications, organ damage and infection. It has special significance for bone marrow transplantation or gene therapy for patients with non cancer diseases such as sickle cell anemia, in which chemotherapy or radiotherapy related toxicity can be avoided It is very important. We still have more work to do before we are ready to translate these findings into human use, but we are encouraged by the results of this study. ”

this study is published in the Journal of clinical investigation