Acute leukemia is a common malignant tumor of the hematopoietic system, characterized by fever, anemia, bleeding and infiltration, with rapid progression, severe disease and high mortality, which is a serious threat to people’s health. At present, combined chemotherapy, bone marrow/stem cell transplantation, immunotherapy, targeted therapy and Chinese medicine treatment are the main treatments at home and abroad. Due to the constraints of insufficient source of stem cell donors, high cost and high risk, combined chemotherapy is still the main treatment for acute leukemia in China, but the toxic side effects such as gastrointestinal reactions, cardiac, hepatic and renal toxicity, bleeding and infections occur in the process of chemotherapy, and a considerable number of patients cannot tolerate chemotherapy. Clinical practice has confirmed that Chinese medicine treatment with chemotherapy can significantly reduce chemotherapy toxic side effects, enhance chemotherapy drug sensitivity and anti-tumor effects, regulate immunity, enhance physical fitness, promote recovery from bone marrow suppression, and improve patients’ quality of life, and patients’ compliance is better than chemotherapy treatment alone. According to the clinical manifestations, acute leukemia belongs to the categories of warm disease, acute labor, hot labor, blood evidence, accumulation evidence, and deficiency labor in Chinese medicine. According to Chinese medicine, the onset of acute leukemia is due to the weakness of the body’s vital energy and the invasion of evil toxins, the onset of internal and external factors, the patient’s congenital deficiency of endowment, or the seven emotions, diet, excessive labor, damage to the liver, spleen, kidney and essence, so that the yin and yang, qi and blood, internal organs dysfunction, internal deficiency of vital energy, and the disease is caused by the six external evil spirits or plague. As the clinical manifestation of acute leukemia is polymorphic, the symptoms vary with the development of the disease and treatment, so it is necessary to adjust the treatment rules and prescriptions according to the changes in the symptoms. According to our clinical experience, we generally divide acute leukemia into three stages, and use Chinese herbal medicine staging combined with chemotherapy to treat acute leukemia with evidence.
I. Pre-chemotherapy treatment.
Before the patient is first diagnosed with acute leukemia and has not yet undergone chemotherapy or recovered from myelosuppression after chemotherapy and is ready to undergo chemotherapy again, the patient’s fever, bleeding and other evil conditions are obvious, and the tumor cells are proliferating vigorously (or the killing effect of chemotherapy drugs on tumor cells has basically disappeared), while the normal hematopoietic function is suppressed, and the signs of positive deficiency are also seen, with fever, sore throat, bone pain, enlarged liver and spleen lymph nodes, skin and mucous membrane petechiae, epistaxis and epistaxis being common. The clinical symptoms include fever, sore throat, bone pain, enlarged liver and spleen lymph nodes, skin and mucous membrane petechiae, epistaxis, epistaxis, even blood in stool, blood in urine, dizziness and weakness, soreness and weakness of the waist and knees, night sweating and low fever, irritability of the five hearts, red or dull red tongue, yellow and dry or grayish black moss, slippery and stringy pulse, the evidence of Chinese medicine is internal heat and toxicity, phlegm and stagnation of phlegm and blood stasis, heat forcing blood flow, and damage to qi and yin. The formula is based on Huanglian Detoxification Tang, Rhizoma Rhizoma Dihuang Tang, Qingying Tang, Scrofula Dissipation Tang, Sijunzi Tang, and Sancai Fengming Dan with addition and reduction. The commonly used herbs are Huanglian, Fried Huangbai, Scutellaria Baicalensis, Shui Niu Jiao, Shengdi, Fried Danpi, Prince’s ginseng, Sheng Bai Shao, Sheng Bai Zhu, Xuan Shen, Zhe Bei Mu, Dan Shen, Jing Tian San Qi, Chuanxiong, Xiao Ji Cao, Snake Berry, White Flowered Snake Tongue Herb, Half Branch Lotus, Long Qi, Shan Dou Root, Xiong Huang, Qing Dai, etc. Modern pharmacological research shows that most of the heat-clearing and detoxifying, blood-stasis-activating and phlegm-dispersing herbs have anti-tumor and immune-regulating effects. Some patients with hypoproliferative leukemia show low peripheral blood triad, severe anemia, and obvious symptoms of positive deficiency at the early stage. At this time, if we use bitter cold to attack and detoxify the blood, it will not only fail to solve the symptoms, but also easily injure the positive, making the positive more deficient and worsening the condition and committing the precept of deficiency. The patient’s blood picture will improve, and then the treatment should be based on eliminating the evil, so as to lay a solid foundation for the patient to enter the chemotherapy period successfully.
Second, chemotherapy treatment.
Systemic combination chemotherapy is still the most basic and main method of modern treatment for acute leukemia. The earlier a patient achieves complete remission, the longer his or her disease-free survival time will be. According to the patient’s systemic condition, induction remission therapy and post-remission therapy are used to enable the patient to achieve or maintain a state of complete remission and prolong disease-free survival. However, during chemotherapy, due to the toxic side effects of chemotherapy drugs, patients often have gastrointestinal reactions, heart, liver, kidney and nervous system toxic reactions, clinical manifestations are mostly seen in nausea and vomiting, poor appetite, abdominal distension and diarrhea, dizziness and palpitations, weakness and night sweating, pale tongue with white coating, thin and moist pulse, etc. Chinese medicine identifies the deficiency of both qi and yin, weakness of the spleen and stomach, loss of harmony in the middle jiao, the treatment is to benefit qi and nourish yin, strengthen the spleen and stomach, resolve dampness and help transport, clinical use of nourishing stomach soup The treatment is to benefit qi and yin, strengthen the spleen and stomach, and resolve dampness to facilitate transportation. At the same time, a small amount of heat-clearing, detoxifying, phlegm-dispersing products are often added, such as white flowered snake tongue herb, half branch lotus, zhebei mum, small thistle, etc., to strengthen the anti-tumor effect with chemotherapy drugs. Experimental studies have shown that zhebei mu and chuanxiong have the ability to reverse drug resistance of leukemia cells and enhance the sensitivity of chemotherapeutic drugs. Thus, the combination of Chinese herbal medicine during chemotherapy can achieve a synergistic effect to reduce toxicity and improve the remission rate of acute leukemia patients. It is worth noting that individual leukemia patients with heavy gastrointestinal reactions during chemotherapy have some difficulties in taking traditional Chinese medicine tonics routinely, so the method of taking traditional Chinese medicine tonics in small amounts and several times frequently can be adopted.
III. Post-chemotherapy treatment.
Leukemia patients often have bone marrow suppression after chemotherapy, which is most obvious 7~10 days after chemotherapy, characterized by dysfunction of internal organs, deficiency of qi and blood, and bone marrow damage. The treatment is to strengthen the spleen and kidney, benefit the qi and nourish the blood, and at the same time to clear the evil toxins, i.e. to support the righteousness as the mainstay and to dispel the evil. It should be noted: the late stage of chemotherapy for leukemia is often the evil is weak, the vital energy, gastric energy, fluids, essence and blood are damaged to varying degrees, treatment should be to support the righteousness and cultivate the root, but do not suddenly enter the warm tonic agent, one is deficient without tonic, the other can lead to closed doors, help the fire to generate heat, easy to cause the residual heat and toxicity of the evil “rekindled”, and commit the actual real harm The second is that the residual heat and toxicity may “rekindle” and cause the real problem. The clinical evidence is often used to strengthen the spleen and kidney Chinese medicine to support the root, with less detoxification and anti-tumor products to remove the residual evil toxins, so that the supplementation does not stagnate the evil toxins, and the attack does not hurt the positive energy. Patients at this stage have obvious decline in peripheral blood triad due to bone marrow suppression, and often fever, bleeding, anemia, etc. can be combined with western medicine to enhance support by means of whitening, anti-infection, hemostasis, blood transfusion, etc., so that patients can safely pass through the bone marrow suppression period. Numerous experiments in recent years have shown that most of the Chinese herbal medicines that benefit qi and nourish yin, strengthen the spleen and tonify the kidneys have the function of regulating immunity to eliminate the tiny residual lesions of leukemia and enhance the function of the body’s immune surveillance system, thus effectively preventing the relapse of acute leukemia, improving the disease-free survival rate and improving the quality of survival and achieving long-term remission.
Fourth, acute is the treatment of its symptoms.
The symptoms of acute leukemia can be treated by treating the symptoms of acute leukemia, such as heat poisoning, blood heat delusion, internal closure and external loss of blood, fever and dizziness. If there is also blockage of Qi in the internal organs, we can add the “Treatise on Typhoid Fever”, “Dipping the heart means dipping the fire, dipping the fire means stopping the bleeding”, so as to remove the heat and stop the bleeding. The clinical evidence can be combined with blood transfusion, anti-infection, dehydration, lowering cranial pressure and other comprehensive measures to quickly control the disease, after the heat toxicity is removed, the fever subsides, and the bleeding is controlled, and then the subsequent treatment is planned.
Fifth, protect the stomach qi at all times.
Chinese medicine believes that “the stomach is alive, no stomach gas is dead”, the stomach is the sea of water and grain, the main intake of decay, to descend for and, like to moisten but not dry; the spleen is the main transport and transformation, rise clear, like dry and not wet. The spleen and stomach are the pivot of the qi flow, all food and drugs are taken in and cooked by the stomach, and the maintenance of the body’s vital activities depends on the transformation of the water and grain essence into qi, blood and yin essence, and the transformation of the water and grain essence is inseparable from the normal transport function of the spleen and stomach. Therefore, when the evidence should be sure to pay attention to protect the stomach, because acute leukemia patients undergoing chemotherapy and the application of a large number of drugs, it is very easy to damage the spleen and stomach, the spleen and stomach injury, the qi and blood biochemical source of kidney essence lost water and grain essence filling, therapeutic drugs are difficult to work, the blood production function can not be restored, the so-called “stomach gas, a hundred drugs difficult to administer”, therefore In the process of treating leukemia in stages, Chinese medicine often adds some products that regulate the qi to help transport and harmonize the stomach to resolve dampness, so as to attack the evil without hurting the middle, and to supplement the deficiency without congestion, often taking Xiang Sha Liu Jun Zi Tang plus reduction, drugs such as Han Xia, Chen Pi, Cardamom, fried Citrus Aurantium, Pelargonium leaves, etc.
Sixth, the research overview and outlook of Chinese medicine in the treatment of acute leukemia.
At present, Western medical treatment of acute leukemia is mainly carried out by repeated and alternating different chemotherapy regimens, and more than half of the patients can obtain complete or partial remission, and a few cases can be cured; however, long-term repeated chemotherapy has the defects of high relapse rate, high toxic side effects, easy to produce drug resistance, and even the occurrence of second tumors. After carrying out bone marrow, cord blood and peripheral blood stem cell transplantation, as well as using gene and immunotherapy, the cure rate of acute leukemia has been further improved. However, the relapse rate of these therapies is still high, and there are difficulties such as lack of donors, complicated techniques, high costs, and high treatment risks with low safety, which are far from satisfactory. Therefore, it is still an urgent and difficult task in the field of leukemia treatment to continuously seek and explore new effective, low-toxic, inexpensive and safe treatment methods and drugs. For example, the success of arsenious acid in treating acute promyelocytic leukemia is an epoch-making milestone and provides a pathway and experience for Chinese medicine research to draw on and reference. The discovery of new anti-cancer drugs from the treasury of Chinese medicine still has important academic and economic values. Throughout the recent years, most of the studies on Chinese medicine against leukemia at home and abroad are either limited to case reports or short-term clinical studies with apparently small observation samples, which are not very convincing and scientific; or they are only experimental studies on animal models or cell lines of leukemia, which have a large gap with the real situation of human leukemia.
Clinical studies have shown that for acute leukemia, the combination of Chinese and Western medical systems can significantly improve the clinical efficacy, significantly improve the patient’s quality of life, prolong the survival period, and Less toxic side effects, low cost. The main elements of the individualized treatment plan of TCM and TCM combination for new leukemia are: according to the specific typology, disease, age, physical condition, cultural background and economic status of leukemia patients, different optimal treatment plans are adopted.
(1) For leukemia types with obvious advantages of Chinese medicine efficacy, such as M3, arsenious acid injection with Chinese medicine discriminative treatment is used as the main treatment, or with all-trans retinoic acid induction for better prevention and treatment of DIC and to achieve the best efficacy.
(2) For types with better efficacy of western drugs but high toxic side effects, such as ALL-L1, AML-M1, M2, M4, etc., western combined chemotherapy with TCM evidence-based treatment is used to reduce toxicity and increase efficacy, improve survival quality, prolong survival period, and strive for long-term disease-free survival or even complete eradication.
(3) For high-risk types prone to relapse and with suitable donors, western combined chemotherapy is first used to induce remission and combined with Chinese medicine discernment treatment to strive for early hematopoietic stem cell transplantation; then combined with Chinese medicine discernment treatment to reduce rejection, promote bone marrow regeneration, reduce transplantation-related mortality and improve clinical cure rate.
(4) For patients with refractory leukemia who are old and frail, or physically weak, including hypoproliferative leukemia, or who have severe damage to important organ functions and can hardly tolerate strong Western medical treatment, treatment with TCM discriminative therapy to support the righteousness and eliminate the evil, or with small doses of differentiation induction (e.g., 30-60 mg/day of retinoic acid, 10-20 mg/day of small doses of cytarabine, etc.) is used.
(5) For relapsed, refractory, multidrug-resistant leukemia patients, in addition to the new, second-line chemotherapy regimen, give full play to the advantages of Chinese medicine and combined Chinese and Western medicine therapies, and actively choose Chinese medicine evidence-based medicine and with arsenious acid injection, etc., which has certain anti-relapse and anti-multidrug-resistant effects.
The success of the development of a number of TCM compound prescriptions that have the ability to increase the efficacy and reduce the toxicity of chemotherapy, improve the quality of patients’ survival and prolong the survival period has greatly encouraged the TCM community to conduct in-depth research on TCM monomers and compound prescriptions for the treatment of acute leukemia and other modern difficult and major diseases. In the post-gene era and stem cell transplantation research boom, how TCM can better exert its characteristics and advantages is currently a hot spot actively explored by the TCM hematology community, and promising first signs of exploration in these fields have been achieved in recent years. It is foreseeable that a more scientific and organic combination of modern gene therapy, stem cell transplantation therapy and TCM therapy will add wings to the tiger and produce a series of brand new prescriptions for the treatment of acute leukemia.