Leukemia, as one of the main types of hematological tumors, is treated by chemotherapy, especially combination chemotherapy. However, combined chemotherapy and bone marrow transplantation are inevitably associated with severe or even very severe reduction of blood cells and are prone to infection and bleeding complications, which inevitably limits the widespread clinical application; undoubtedly, elderly and frail patients, as well as patients who relapse after chemotherapy or even transplantation, find it difficult to tolerate and administer chemotherapy again. There is no doubt that elderly and frail patients, as well as patients with chemotherapy and even post-transplant relapse, have difficulty in tolerating and re-administering chemotherapy. This is a difficult problem in front of doctors and patients. As far as I know, in the 1980s and 1990s, non-chemotherapy drugs were gradually developed, either alone or in combination with chemotherapy, to achieve control, remission and even cure of leukemia!
In terms of chemotherapy, we often encounter patients who are unable to accept or tolerate it, or who are not effective or even ineffective with chemotherapy alone, as well as those who are relapsed and resistant to chemotherapy, etc. We take this opportunity to talk with our colleagues, patients and their families about non-chemotherapy drugs and treatments for leukemia.
One of the non-chemotherapy means: induction of differentiation and apoptotic agents Remember that it was the late 1980s, one of the types of leukemia, acute promyelocytic leukemia, the effect is not good, due to complete blood cytopenia and easy to combine serious bleeding complications – diffuse intravascular coagulation and other difficulties in the implementation of conventional chemotherapy treatment, making a considerable number of patients At this time, Professor Wang Zhenyi and his team developed all-trans retinoic acid (which can induce differentiation of leukemia cells, promote maturation and transformation into good cells, thus relieving leukemia), and since then, this drug has made this type of leukemia the one with the best prognosis, which has opened the journey of non-chemotherapy treatment of leukemia. Arsenic (tumor cells are uncontrolled infinite proliferating cells, arsenic has the ability to promote apoptosis of tumor cells, that is, to promote apoptosis and death, thus eliminating tumors) was developed in the northern cities of Harbin and Dalian for the treatment of acute promyelocytic leukemia with arsenic oral compound tablets (containing Xiong Huang, Qing Dai, etc.) and arsenic intravenous injection (arsenic trioxide developed from highly toxic arsenic). This is a great contribution of Chinese medicine to the world of hematology! In recent years, I have met some patients with acute promyelocytic leukemia who had relapsed from western hospitals and were treated with oral arsenic, together with the intervention of Yi Qi, Yin and reconciliation soup, to obtain remission again and long-term survival.
In the 1980s, when I first entered the clinical field, the old doctors had a saying: “Slow granulocytic leukemia is not treated for three or four years”; although it was not very pleasant, it reflected to a certain extent the actual problem of limited therapeutic effect at that time. When I went to Guangzhou to work in the early 20th century, I heard that some hospitals in Hong Kong were recruiting patients with slow-onset leukemia for clinical drug studies, and one patient received information and fought to enter the study. The second and third generation products have been released and are in clinical and preclinical status; Imatinib targeted drug not only treats slow-onset leukemia with great success, but also controls the proliferation of leukemia cells. leukemia with great success, but also for the treatment of certain types of acute lymphoblastic leukemia, idiopathic hypereosinophilic syndrome and other special types of disease, also obtained good results; clinically, due to Gleevec-induced hematocrit hinders the continued application to obtain good results, some patients taking drugs smoothly, but failed to obtain the expected biological remission effect, and so on, such patients, find me In the clinic, I met two patients with slow-onset leukemia who had allogeneic bone marrow transplantation in time because they happened to have a perfectly matched hematopoietic stem cell donor, and in the subsequent dynamic monitoring of micro residual disease, they had positive manifestations of fusion gene. But they could not afford the financial burden, so they approached me for Chinese medicine intervention. Although the number of cases is too small to be too sure of the efficacy, it has been observed that the genes related to the occurrence of the disease have been improved by the Chinese medicine treatment.
More and more studies have found that the occurrence and evolution of leukemia is closely related to the mutation of its genes and chromosomal aberrations; recently, some drugs targeting genes have been gradually developed, in addition to the above-mentioned classical Gleevec targeting the BCR/ABL fusion gene, another prominent gene, FLT-3, whose mutation is closely related to the occurrence and prognosis of acute myeloid leukemia, despite the availability of The clinical effect is far inferior to that of Gleevec, and medical experts are exploring it relentlessly; it is also the duty and responsibility of our workers who are engaged in the treatment of leukemia with Chinese medicine.
The third means of non-chemotherapy: biological response regulators such as interferon, interleukin, tumor necrosis factor and its biological immune cells, etc., are to inhibit and eliminate the malignant proliferation of cells and control the effect of leukemia, the body originally has such biological regulators and biological immune cells, but the activity is low, it is difficult to play a control effect, and then destroy the role of tumor cells, exogenously given, play a corresponding role In clinical practice, interferon used to play a major role in the treatment of chronic granulocytic leukemia; today, it still plays a role in the treatment of certain leukemias after remission of microscopic residual disease and the treatment of certain refractory relapsed leukemias with adjuvant chemotherapy. I have written and published an article in the national-level publication “Chinese Journal of Integrative Medicine”, and have continued clinical exploration and found that Chinese medicine interventions play a role in bioresponse modulation to varying degrees, and play a role in increasing efficiency and reducing toxicity, so I hope to continue to explore and further improve clinical effects.
In recent years, with the development of epigenetics, the development of anti-methylation drugs has been successful, and the representative drug is decitabine (trade name “Dacor”), which was initially implemented for the clinical treatment of myelodysplastic syndrome (formerly called pre-leukemia) with increased primitive cells. Afterwards, it was gradually applied to the treatment of acute myeloid leukemia, mainly for elderly and refractory patients, and it did have certain efficacy in improving the remission rate. Subsequently, we encountered a patient with refractory AML who did not achieve remission despite 2 courses of Dacor+pre-excitation chemotherapy, indicating that a combination of therapeutic interventions is still needed, especially we are exploring herbal interventions to enhance support and improve the remission rate and quality of life, etc.
The fifth non-chemotherapy means: anti-angiogenic agents Review of the literature, found that in the 1950s, foreign production of a drug for the treatment of nausea and vomiting reactions in pregnancy, called: reaction stop (thalidomide), after taking the anti-vomiting effect is very good, but after the birth of the child, many appear limb deficiency can not afford, medical called “seal fetus However, after birth, many children have deformed children with limb deficiencies, medically known as “seal fetus”, and then this drug was banned. In the past ten years or so, because it was found that tumor cells have enhanced angiogenic activity and promote tumor cell proliferation, how to control it, research found that reaction stop has the effect of inhibiting angiogenesis, thus may play a role in controlling tumor cell proliferation effect, applied in multiple myeloma to play a certain effect, gradually used in the treatment of certain types of leukemia, expect to play some auxiliary effect; its second generation products: Renalidomide The efficacy is better than the former, which is worth further exploration.
Non-chemotherapy means of the sixth: monoclonal antibodies For leukemia cell surface-specific antigens, such as CD33, CD52, CD20, etc., especially the latter CD20, monoclonal antibodies have been successfully developed: Meroval (rituximab), applied to lymphoma has played a good effect, although mainly used in the treatment of certain types of malignant lymphoma, however, for B lymphocyte type leukemia However, for B-lymphocyte type leukemia, such as chronic lymphocytic leukemia, hairy cell leukemia and its BCR/ABL-positive acute lymphocytic leukemia patients, it is possible to consider single drug or combination chemotherapy treatment, which is expected to obtain further control and then remission of the disease; CD33, CD52 and other related monoclonal antibody drugs are being improved and studied in clinical trials; I am committed to explore the clinical intervention of Chinese medicine to assist monoclonal antibody I am committed to exploring Chinese herbal medicine as an adjunct to monoclonal antibodies for leukemia.
The histone acetylation/deacetylation modification is the key to the regulation of gene transcription, if the regulation is disrupted, the gene expression will be out of control, and the body will develop tumor/leukemia. In clinical practice, I have treated a patient with acute myeloid leukemia transformed by myelodysplastic syndrome, who needed to take sodium valproate due to previous depression, and insisted on the treatment with sodium valproate during several years of combined Chinese and Western programs. Of course, it is only a case, pending our unremitting efforts to strive for.
It is indisputable that, overall, combination chemotherapy is still the basic, mainstay of treatment for leukemia as opposed to the non-chemotherapy options mentioned above, and the intensity of chemotherapy has gradually increased along with the strengthening of supportive therapies, resulting in increasing efficacy in terms of near-term remission and long-term disease-free survival! However, there is a limit to what the body can tolerate, and it is particularly encouraging to see that many non-chemotherapy drugs are gaining significant clinical efficacy. With the continuous emergence of non-chemotherapy drugs developed for different pathogenesis and targeting different “points”, new non-chemotherapy single agent or combination chemotherapy regimens are about to bring epoch-making effects, and it is believed that a new era of leukemia treatment will be ushered in in the near future!
Clinically, for patients who have relapsed from chemotherapy or even bone marrow transplantation, elderly patients, difficult-to-treat patients with ineffective chemotherapy, or those with organ damage and physical decline, or those who find it difficult to receive chemotherapy for various reasons, we are constantly trying to combine Chinese medicine with non-chemotherapy regimens in order to bring hope and efficacy to patients. The preliminary research and exploration found that some of the Chinese herbal components also have some of the above-mentioned non-chemotherapy anti-leukemia effects, and the intervention of the relevant non-chemotherapy drug composition program treatment, to obtain certain results.