Children's leukemia does not have to "slow medicine"

Children's leukemia does not have to "slow medicine"

June 27, 2017 Source: Science Network

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When it comes to childhood leukemia, most parents will smell it. At present, there are about 2 million children with leukemia in China, and about 30,000 to 40,000 people are added each year. In children with malignant tumors, the incidence and mortality of leukemia are the highest. This kind of malignant disease is a serious threat to the child's life and health, and it also brings a great burden to the family and society.

Conventional conventional chemotherapy is the primary means of treatment for leukemia, and it follows the concept of the maximum tolerated dose of the dose "the higher the better." However, high-dose chemotherapy has brought about two prominent problems of toxic side effects and high cost while improving the long-term survival rate of patients.

Can this traditional concept be broken in the treatment of childhood leukemia? Wang Qianfei, a researcher at the Beijing Institute of Genomics, Chinese Academy of Sciences, and Hu Shaoyan, director of the Department of Hematology, Children's Hospital of Suzhou University, have tried to use low-dose chemotherapy as the first-line treatment for first-time diagnosis of childhood leukemia. Recently, breakthroughs have been made.

"Conventional high-dose chemotherapy also promotes the growth of drug-resistant cells while rapidly killing most sensitive tumor cells." Wang Qianfei said, "At present, the lack of low-dose chemotherapy in the medical community has a serious understanding of the role of the patient's leukemia genome. The clinical promotion and application of the chemotherapy regimen under the guidance of this new concept."

The potential mechanism of action of the low-dose chemotherapy regimen is to stimulate the leukemia cells to enter the cell cycle through the cytokine G-CSF, and to enhance the sensitivity of leukemia stem cells to chemotherapy drugs, so that they can be killed by low-dose chemotherapy drugs. However, this regimen has long been used as a backup adjunct therapy for palliative care in adult leukemias, especially in elderly patients who cannot tolerate high-dose conventional chemotherapy.

"Children's leukemia has different drug sensitivity and genomic characteristics than adult leukemia. For example, the number of mutations is small, the expression of apparent regulatory genes is rare, and the proportion of genes carrying tumor fusion genes is different from that of adults." This made Wang Qianfei and others think about whether they can use them. Accurate genomic medical means to maximize the elimination of mutant tumor cells and reduce recurrence?

The research team pioneered the use of a single dose of conventional chemotherapy combined with the cytokine G-CSF "low-dose regimen" as an induction mitigation regimen for the treatment of acute myeloid leukemia in children, using the latest genome sequencing technology to track tumors throughout the process. Cell clearance.

They have evaluated the clinical efficacy of 140 children in the past five years. The results show that the "low-dose regimen" has similar efficacy and survival rate to the existing conventional chemotherapy regimen, and can significantly reduce chemotherapy side effects and treatment costs.

Hu Shaoyan said that in the early stage of clinical research, low-dose chemotherapy is only used in children with intolerance, such as severe infection or poor constitution, and has achieved good therapeutic effects. It has been extended to all applicable children with acute myeloid leukemia. .

According to statistics, the long-term disease-free survival rate reported by China's single center is 20-40% lower than that of developed countries. A large part of the reason is that as a developing country, many hospitals support imperfect treatment conditions, and patients cannot afford conventional high-dose chemotherapy. Strong toxic side effects. The implementation of low-dose chemotherapy is expected to improve this situation.

In addition, the low-dose chemotherapy program also significantly reduced the cost of treatment, saving 30,000 to 50,000 yuan per person, so that more patients get treatment opportunities. "In the past, children with leukemia gave up more than 30% of the treatment, and the use of low-dose regimen reduced the rate of abandonment treatment to less than 5%." Hu Shaoyan said.

From this perspective, the clinical promotion of low-dose chemotherapy has the potential to achieve universal medical care. On June 26th, the Beijing Institute of Genomics of the Chinese Academy of Sciences and Suzhou Children's Hospital jointly established the "Precision Medical Research Center", which will promote multi-center large-scale clinical trials of low-dose chemotherapy.

In a follow-up study, the researchers will work to reveal the molecular and clinical characteristics of patients with low-dose regimens, establish a clinical protocol evaluation system based on genomic analysis, and ultimately achieve stratified treatment of childhood leukemia.

"The tumor genome is constantly evolving under the intervention of chemotherapy, and the evolutionary model directly affects the development of the disease and the future recurrence." Wu Zhongyi, a world famous group geneticist and a candidate for the "Thousand Talents Program" and a member of Taiwan's "Academia Sinica", believes that " Animal studies and mathematical models have shown that low-dose chemotherapy can effectively reduce the occurrence of drug resistance, and the implementation of low-dose chemotherapy has far-reaching significance for the use of tumor genome evolution theory to guide clinical treatment." (Ding Jia)

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