I. Historical review of chronic leukemia
After more than a century and a half since the symptoms of leukemia were first described, it has been gradually recognized that leukemia is actually a highly heterogeneous group of diseases, especially due to the development of testing techniques. The hematologic features of autopsies first attracted the attention of early leukemia researchers. According to Gunz and Henderson, although leukemia was noted as early as 1811, the first precise description of leukemia is generally believed to have been published by Velpeau in 1827. Further observations were subsequently made by Barth and Donne and Craigie. The recognition of leukemia as a separate disease, however, is attributed to reports by Bennett in Scotland and Virchow in Germany in 1845. The typical cases were John Meredith, a 28-year-old salesman from Edinburgh, and Marie Straide, a 50-year-old cook from Berlin. Both patients had felt ill for 1.5 to 2 years, and they had progressive deterioration, including progressive weakness, hemorrhage, and other symptoms. The distinctive features of both cases at autopsy were a giant spleen and a persistent increase in the blood cell component, especially the leukocyte component. 1846 was the year Fuller first diagnosed leukemia in either patient, and the first case of leukemia was reported in the United States in 1852 in a 17-year-old fisherman from Philadelphia, followed by several other cases, mostly from the Boston area.
Early attempts to distinguish between different types of leukemia included Virchow’s classification of leukemias of splenic and lymphoid origin, each associated with a specific type of leukocyte, a division roughly identical to that of myeloid and lymphoid leukemias. in 1870, Neumann made the important addition that “splenic cell leukemia of cells actually originating from the bone marrow.” In 1889, Ebstein was the first to use the term “acute leukemia” in clinical practice, until then it had been assumed that leukemia was a chronic disease, and Ebstein also found that acute leukemia was different from the “acute change” of chronic leukemia. It was soon discovered that acute leukemia had a very short survival period, while chronic leukemia had a slightly longer survival time.
Table 1 Milestones in the history of chronic leukemia
Year Event
1845 Recognition of leukemia as a group of diseases (probably CML)
1846 First diagnosis of leukemia in a living patient
1865 First treatment of CML with Fowler’s solution
1891 Development of blood cell staining techniques
1895 Discovery of x-ray irradiation
1924 Recognition of CLL as a separate clinical syndrome
1934 Experimental methods to confirm the malignant nature of leukemia
1946 Effective chemotherapy for leukemia, nitrogen mustard
1960 Identification of the Philadelphia chromosome
1966 Recognition of leukemia as a cellular proliferative disease
1966 Introduction of leukocyte debulking in the treatment of CML
1973 Recognition of the identity of one chromosome at position (9;22)
1978 Introduction of autologous transplantation for CML
1984 First description of the role of BCR in CML
1990 Demonstrated that ABL-BCR gene can cause CML-like disease in mice
Domestic, 1948 Deng and Forkner reported a case of eosinophilic leukemia
Fowler’s solution, a 1% arsenic trioxide solution, was the first solution useful in the treatment of CML. 1865, Lissauer’s patient was dying before receiving Fowler’s solution, and after receiving Fowler’s solution, his condition improved and This state lasted for several months. Since then arsenic has been used to treat CML for about 30 years. Appropriate doses control fever, lower white blood cell counts and reduce the size of the spleen, reduce pruritus and pruritus, and improve anemia.
Table 2 Brief history of CML treatment
1930～ Organic arsenic solution
1950～ Splenectomy, splenic area radiotherapy, busulfan (BU)
1970～ Hydroxyurea (HU)
1980～ Interferon alfa and interferon alfa-based therapy
(interferon alpha + BU/HU/AraC/trichostatin/other), hematopoietic stem cell transplantation
1999~ STI571 or Imatinib Mesylate (Gleevec/Glivec, Gleevec)
A brief history of CML treatment over nearly a century. Evidence-based medicine has concluded that leucovorin (Marilan) is more effective than splenic area radiotherapy, hydroxyurea is superior to Marilan, and spleen excision is ineffective. Understanding the pros and cons of the available treatments allows for the design of an individually tailored treatment plan for the patient. The ultimate goal of treatment is to achieve durable clearance of the Ph clone or molecular remission, for which there is no cure except allogeneic hematopoietic stem cell transplantation. The secondary goals are to prolong the chronic phase, improve quality of life, and prevent progression, because once progression occurs, there is little effective treatment.
CML-CP is the critical period of treatment and the expiration date of treatment. the treatment of CML-AP and CML-BP phases is the same as that of acute leukemia. The focus here is on CML-CP treatment.
II. Treatment characteristics of TCM.
(a) “Simple, convenient, inexpensive and experimental”
Simple: “simple but not simple”
Convenient: convenient
Cheap: cheap, inexpensive, suitable for the grassroots
Test: effective and effective. This is the key.
Cure the head and tail, find the right patient group: the disadvantaged and traditional culture believers, such as Lin Daiyu portrayer Chen Xiaoxu, Anita Mui, etc. There are also negative examples, such as a master like Liang Qichao, who died young because of his superstitious belief in Western medicine and ended up cutting off his right kidney, which was not diseased, a big event in modern Chinese cultural history. According to the medical records of Liang Qichao that were later made public, Liang underwent a nephrectomy in the hospital in March 1928 and died in January 1929, less than a year later at the age of 57, which was undoubtedly a great loss for a master of national education. According to the information, Liang Qichao was suffering from tuberculosis of the left kidney, which was diagnosed by experts from Germany and Peking Union Medical College Hospital as having extensive necrosis and renal insufficiency. However, because the right kidney is intact certainly will not appear uremic syndrome, after the right kidney was mistakenly cut, the left kidney can not compensate properly, and soon will appear uremic syndrome.
The entertainment industry, such as Luo Jing, Ma Hua and Li Yuanyuan, are all empty of money and regret.
(II) Flexibility and diversity
The Sun Tzu? The book of reality and emptiness: “Soldiers have no permanent situation, water has no permanent shape; those who can win because of enemy changes are called gods.”
Diversity in soldiers: Chinese herbal medicine is like the minerals spread all over the earth, inexhaustible.
Diversity in dosage forms: creams, pills, pans, and injections; internal treatment, external treatment, and both internal and external treatment, such as Chinese herbal soup and Chinese patent medicine taken internally and Qing Dai or Qing Huang San applied externally
(iii) Relatively less toxic side effects, which patients are willing to accept
especially the old and weak patients.
Sun Tzu? The warfare chapter: “Those who do not know all the harm of the army cannot know all the advantages of using the army.”
Sun Tzu? The whole army is the highest, and the broken army is the second.”
(iv) Specific treatment strategies
The average natural course of untreated chronic granuloma is 31 months, and the survival period has been prolonged by drug treatment, and there are many disease-free long survivors using allogeneic bone marrow transplantation.
Once chronic granulocytes enter the accelerated or acute phase, there is a lack of satisfactory therapeutic measures to reverse the disease, so effective control of the disease progression in the chronic phase of chronic granulocytes is an important measure to prolong the life of patients. The rationale for drug treatment of chronic granulocytes is to reduce the number of genetically unstable clonal cells in the chronic phase, to reduce the chance of the first genetic mutation, and to hinder the progression from the chronic phase to the acute phase. In recent decades, hematologists have been devoted to exploring an effective drug treatment regimen that can reduce the tumor load to a minimum without causing serious toxic side effects and inducing acute changes.
C. Chinese medicine treatment
In the past 10 years, there is a consensus in the literature of Chinese medicine on chronic granuloma: the pathogenesis is characterized by “deficiency, stasis and toxicity”, the symptoms are characterized by deficiency of the root and the symptoms of the symptoms, and the treatment is a combination of disease and evidence, and the main treatment method is to clear heat and detoxify, clear liver and fire, activate blood circulation and remove blood stasis, and support the correct energy (qi, blood and yin). . The clinical efficacy is only to improve symptoms, achieve clinical and hematological remission, and prolong the chronic phase.
(i) Discriminatory treatment.
Discriminatory treatment is the basic approach and the main feature of TCM in the treatment of any disease, and the treatment of slow granuloma is no exception.
There is no unified opinion on the TCM classification of chronic granulomatous disease, but from all perspectives, it is roughly divided into.
Yin deficiency and internal heat, blood stasis and internal obstruction, Qi and blood deficiency and heat toxicity congestion, respectively, choosing Artemisia annua and turtle nail soup, diaphragm down and eliminating blood stasis soup, Bazhen Tang and Qing Ying Tang combined with Rhizoma Dihuang Tang.
On the basis of this, we can add and subtract flexibly, such as adding herbs with modern pharmacological empirical research but also anti-tumor drugs, such as Half Branch Lotus, White Flowering Snake Tongue Herb, Seven-leaved One-branch Flower, Mountain Cichlid Mushroom, Curcuma longa, Coix Seed, Turmeric, Artemisia, Swelling Maple, Deer Artemisia, Xiong Huang, Arsenic, Zebra, Toadstool, Shou Gong, etc.; or combining with Chinese patent medicines for internal and external treatment, the variations are endless. This is the so-called “soldiers have no permanent power, water has no permanent shape”.
(2) Compound or single prescription single medicine
(1) Angelica Long Huo Wan: 10~30g, taken orally twice daily.
2) Qing Dai: divided into capsules, 2-4g each time, 3 times a day, swallowed after meals.
3) Qing Huang San: The ratio of Qing Dai and Xiong Huang is 9:1, divided into capsules, 3~5g each time, taken orally 3 times a day. After remission, maintain the blood picture in the normal range with a maintenance amount of 3-6g per day.
4) Liushen Pill: 30 capsules/dose; 3 times daily, orally.
5) Cancer Spirit No. 1: Injection, consisting of arsenic containing 1mg of arsenic trioxide and light powder containing 0.01mg of low mercury chloride, 2.0ml each.
(6) Plum Blossom Dotted Tongue: 30 capsules daily, divided into 3 times with warm water.
7）Niuhuang detoxification tablets: 3 to 4 tablets each time, taken orally twice daily.
8）Rhubarb Stinging Worm Pill: 1 pill each time, 2~3 times daily, take it with warm water. Pientzehuang or Xinhuang Tablet
9) Anti-white Spirit: 3~5 capsules, take it after meal twice a day. (Tao Shuchun 1992, 1997).
10) Ridhecon: shandoo root, flea hue, Qing Dai, stinging worm, curcuma-activate blood and detoxify (Li Xiaohui 1999).
(11) Clearing liver and resolving blood stasis soup (Wang Xueyou 1996).
12) Fu Zheng Cancer Suppressing Punch: Roasted Astragalus, Radix Angelicae Sinensis, Radix et Rhizoma Polygonati, Dry Lotus Grass, Radix Rehmanniae, and He Shou Wu for micro residual leukemia. (Zhou Aixiang 1996).
3. Arsenic preparation
Arsenious acid 10ml plus 5% glucose or 0.9% saline 500ml, 1 time a day, intravenous, 30 days as a course of treatment.
Shen Nong Ben Cao Jing: “Male yellow, …… main cold and heat, rat fistula, malignant sores, gangrene hemorrhoids, dead muscle” “female yellow, …… main malignant sores head baldness, ringworm, scabies. Kill poisonous insects, lice, body itch.” Arsenic was first contained in the “Kai Bao Ben Cao”. The compendium of materia medica: “raw for arsenic yellow, refined for arsenic.” “Arsenic sex as fierce as brave, so the name. But out of the letter state, so people call for the letter stone, and hidden letter word for people say.” Male yellow is the main component of arsenic sulfide (AS2S2), containing 75% arsenic, sulfur 24.9%. Female yellow for arsenic trisulfide (AS2S3), containing 61% arsenic, 31% sulfur, alias Huang An, Kunlun yellow, arsenic. Arsenic is the main component of arsenic trioxide (AS2O3).
4.Indigo red and its derivatives isoindigo a
Indigo red is the active ingredient extracted from cyanide. Isoindigotin (methylisoindigotin) was successfully developed by the Chinese Academy of Medical Sciences after more than 20 years, and is the first bisindole antitumor drug in China. The dosage is 75-150mg per day, divided into 3 consecutive doses until the leukocyte count drops to 4.0×109/L and the drug is stopped. The side effects include nausea, poor appetite, abdominal pain, diarrhea and even blood in the stool. In addition, there are different degrees of bone and joint pain. It is not widely used because the side effects are greater than HU and the efficacy is less than HU. This drug also cannot eliminate Ph clone and cannot prevent acute changes.
Indocyanine treated 314 cases of slow granules, with an efficiency rate of 87.26%, a remission rate of 59.87%, a median survival of 31.5 months, and an average survival of more than 6 years for those in remission. Nearly half of the patients had side effects such as abdominal pain and diarrhea, and mucus-like blood stools could occur in 6.97% of the patients.
In 1982, the Institute of Pharmaceutical Sciences of the Academy of Medical Sciences directed the full synthesis of methylisatin, which overcomes the poor solubility of indigo red and gastrointestinal side effects, and the efficacy is improved. 374 cases of national phase III clinical observation in 1997, the total effective rate of 90.1%, remission rate up to 81.3%. The remission effect is good, reaching the best efficacy time of 73.3 days, the median survival period of 43 months, the average survival period of remitters is 53.77 months, the longest one reaches more than 109 months. The main side effect is skeletal and joint pain.
Isoindolizumab can be combined with hydroxyurea. Isoindolizumab is the main drug for maintenance treatment of slow granules.
5.Triptolide (harringtonine, HT)
It is a kind of plant base, which is unique to China. In 1984, the use of HHT for the treatment of CML and other myeloproliferative diseases was reported in China, but the number of cases was small. In 1995, O’Brien and Kantarjian et al. reported the treatment of patients with late CML-CP stage with hypertrigonelline 2.5 mg/(m2?d) intravenously for 14 days and then 7 days per month for 6 months. 2/3 of the patients had CHR, and more than 50% of them were resistant to IFNα. O’Brien et al. reported in 1999 the treatment of early CML-CP with The rates of CHR and major genetic remission (Ph+≤35%) were 92% and 27%, respectively. Subsequent reports have been made with HHT combined with low-dose Arac or IFNα or others.
6.Artesunate
The active ingredient extracted from the Chinese medicine Artemisia annua, initially used for the treatment of malaria, is now widely used in malignant tumors, including leukemia, and immune diseases.
At present, many other scholars in China treat chronic granulocytic leukemia with Chinese medicine, such as Qing Huang San from Xiyuan Hospital of the Institute of Traditional Chinese Medicine, Anti-Bai Dan (Qing Dai, Xiong Huang, Ba Dou, Chuan Wu, Lactuca, Yu Jin Xiang, Betel nut, Zhu Sha), and Niu Huang Detoxification Tablets (Xiong Huang, Niu Huang, Raw Rhubarb, Raw Gypsum, Radix Platycodon, Bing Qi, Licorice) from Shanghai College of Traditional Chinese Medicine. Zijin ingots (Shancii mushroom, Xionghuang, Zhu Sha, Daji, Qianjinzi cream, musk, Wu Bei Zi) from Jiamusi Central Hospital and Guangzhou No.1 Hospital and Liushen Wan (Niuhuang, Toadstool, musk, Xionghuang, pearl, ice chips) from Tianjin College of Traditional Chinese Medicine. Dalian Institute of Traditional Chinese Medicine and Hematology’s White Blood Kang (Qing Dai, Xiong Huang, Dan Shen, etc.) have better efficacy, which are all based on Xiong Huang, a yellow mineral containing arsenic sulfide, which is toxic to the bone marrow, but has toxic effects on the liver and kidneys, and chronic arsenic poisoning and even death can occur if the dose is not well controlled.
Angelica rehmannia pill is an effective adult medicine for the treatment of slow granules, of which Qing Dai is an effective drug for the treatment of slow granules. Therefore, at present, the effective Chinese medicine treatment mostly uses Qing Dai and Xiong Huang.
(C) folk remedies (rituals seeking the wild)
1.Toad
Take 15 125g heavy toads, dissect the abdomen and remove the internal organs, wash them and add 1500ml of yellow wine, put them into a porcelain jar and close them, then put them in an aluminum pot, add water and boil them with fire for 2 hours, and filter the liquid to get them.
2, yellow root pig bone soup
50g of yellow root, 1200g of pork bone, decoction of the above 2 flavors with water, 1 dose daily, divided into 4 doses.
Combination of Chinese and Western medicine
1.Treat the symptoms according to the characteristics of each stage of slow granulocytes, form a fixed formula, add or subtract according to the symptoms, and cooperate with chemotherapy in the accelerated or acute change stage.
2.The Chinese medicine (or active ingredients) that have been confirmed by clinical and experimental research to have positive efficacy on slow granuloma, such as indigo red, isoindigo nail, Qing Dai, etc., are applied alternately or in combination with commonly used chemotherapeutic drugs, such as hydroxyurea, white elimination, etc., in each stage of treatment.
3, in the process of slow particles treatment, according to the different stages of the use of chemotherapy at the same time, identification and treatment with Chinese medicine treatment, acute change or end-stage with combined chemotherapy method.
In the different stages of slow granulation treatment, the combination of Chinese and Western medicine methods, the synergistic effect of Chinese and Western medicines, the therapeutic effect of the combination, not only can reduce the total amount of chemotherapy drugs and the duration of drug use, but also can avoid or reduce adverse reactions and complications, while alleviating clinical symptoms, improve the quality of survival, fully reflect the advantages of combining Chinese and Western medicine.
According to the statistics of relevant literature in the past 10 years, the complete remission rate of traditional Chinese medicine in the treatment of chronic granuloma is 45%~80%, the total effective rate is 80%~90%, and the median survival period is between 31.5~65 months; the complete remission rate of combined Chinese and Western medicine in the treatment of chronic granuloma is 80%~90%, the total effective rate is 83%~98%, and the median survival period is between 57.6-76 months. The median survival was between 57.6-76 months. There are also individual reports of cases with long-term survival of more than 10 years. From the above figures, the complete remission rate and the total effective rate of combined Chinese and Western medicine treatment of chronic granulocytes are higher than those using Chinese medicine alone. From the analysis of clinical data, although the remission rate is low and the time to achieve remission is longer when using Chinese medicine alone compared to chemotherapy, Chinese medicine has fewer side effects and is safe for long-term use. The complete remission rate of combined Chinese and Western medicine treatment was higher than that of those who used Western medicine alone, and the median survival period and time to acute change were also longer than those treated with Chinese medicine or Western medicine alone, and were better than the chemotherapy group alone in terms of clinical symptoms, signs, and hematological remission.
Conclusion.
Chronic granulocytosis is a common leukemia, and treatment with Chinese and Western medicine has obtained positive efficacy. Timely and appropriate use of combined Chinese and Western medicine treatment can improve the efficacy, prolong the chronic phase, and stop and delay the arrival of the accelerated and acute phases. The key period of chronic granulocyte treatment is the chronic phase. Genetic and biological remission is the ultimate goal of chronic granulocyte treatment.