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by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

The Nature of Leukemia

Leukemia is the term applied to cancers in which one line of bone marrow stem cells that produce white blood cells (leukocytes, the immune system cells) undergo neoplasia. The transformed cells uncontrollably yield an abnormally large amount of the corresponding white blood cells, mainly in an immature form. Also, by proliferating in numbers, the neoplastic stem cells crowd out the other stems cells in the marrow, so that there are fewer of the red cells and platelets, as well as other lines of white blood cells able to be produced. The destructive aspect of the disease is often manifest first by the lack of these other cell types, producing anemia and spontaneous hemorrhage. Eventually, the internal organs (initially the liver and spleen) swell up with the excess white cells, causing further problems. In addition, the leukemic cells usually have substantially reduced immune functions, leading to high incidence of infections (1).

Different types of leukemia are identified by the stem cell line involved. There are two major categories: lymphocytic and myelogenous; the latter is sometimes divided into myelocytic, monocytic, and granulocytic leukemias, depending on the analysis used. Two somewhat similar bone marrow diseases are polycythemia (with excessive production of red blood cells) and thrombocythemia (with excessive production of platelets).

Depending on the severity with which the leukemia manifests, it may be classified as acute or chronic; despite these names, acute leukemia does not have the meaning of a self-limiting temporary disease: without treatment it can be fatal within 2-4 months. Generally, acute leukemia is characterized by very large numbers of immature lymphocytes (known as lymphoblasts) or large numbers of myeloblasts (the "blasts" are immature cells; this leukemic condition is sometimes called myeloblastic leukemia). Chronic leukemias can flare up with an acute phase, producing a huge production of blast cells, yielding a "blast crisis" that is often the fatal phase of the disease.

It is common practice to label the leukemias by initials for easy reference: ALL (acute lymphocytic leukemia), CLL (chronic lymphocytic leukemia), AML (acute myelocytic or myeloblastic leukemia), and CML (chronic myelocytic leukemia). The leukemias are further subdivided according to the patterns of cells seen by microscopic examination of the blood, revealing different cell sizes, degrees of maturation of the cells, cell surface markers (especially immunological components), and proportions of different cell types. These divisions may be of importance, in that the treatment strategies can vary according to the observed condition; the results of these tests can also help the oncologist advise the patient regarding prognosis.

The possible causes of leukemia include exposure to ionizing radiation, exposure to some chemicals (benzene is an established example), and the action of viruses (e.g., HTLV, human T-cell leukemia virus, a type of retrovirus). Genetic factors play a role in susceptibility, especially for the childhood leukemias. Except for the possibility of attempting an antiviral treatment for virus-induced leukemias, the causes of the disease do not shed much light on the treatment to be given. Even in the case of a viral causation, if suppression or elimination of the virus could be accomplished, that might not cure the disease; the cellular transformation that occurred may no longer reversible.

Some cases of chronic leukemia, notably CLL, are sufficiently innocuous that they are left without treatment for a time because the degree of imbalance in blood cell production is within tolerable limits; in most other cases, anticancer drugs are used in an effort to slow its progress. Some new techniques of treating leukemia have been developed, include destroying the cancerous bone marrow (thus eliminating the neoplastic cells) and transplanting healthy bone marrow (grown in the laboratory from donated marrow cells).

Substantial success has been attained in treating acute childhood leukemia, especially ALL, which was, until recently, a major cause of childhood deaths (with peak incidence around 4 years of age). This positive outcome may be the result of two factors: in acute leukemia, the chemotherapeutic drugs have a much stronger effect on the highly active abnormal cells than on the normal cells; and in children the ability to recover normality is better than in older persons. Up to 90% of cases of childhood acute lymphocytic leukemia go into remission with treatment, with about 70% of treated cases gaining long-term survival (2). AML tends to strike in the age range of 15-39 years and has a moderately good response to treatment by bone marrow transplant, though long-term outcomes are not yet known.

Cases of chronic leukemia are poorly managed by modern chemotherapy: the disabling effects of the therapy on the entire physiological function are often as strong as they are on the cancerous cells. Often, the individual must undergo multiple types of interventions, including blood transfusions, antibiotics, and other "supportive therapies." Progress towards a cure has been difficult. The age of diagnosis for chronic leukemia is typically between 40 and 60 years. Without treatment, chronic leukemia patients are expected to live for 2-6 years from onset of the disease; CML tends to progress more rapidly than CLL. However, about half of the patients with chronic leukemia die within two years of their diagnosis even with treatment. Slightly increased survival time after diagnosis in recent years may be the result of earlier detection more so than successful treatment. Busulfan (a.k.a. Myleran), a drug that has been frequently used for one type of chronic leukemia (granulocytic), commonly produces mean survival times of about 3-4 years. For leukemia in adults, it is reasonable to pursue Chinese medical therapies in an attempt to improve the outcomes.

Chinese Medical Approaches

The ability to diagnose leukemia, which requires assay of blood cells, came to China with Western medicine, and was attained there about 60 years ago. Prior to that, leukemia patients must have presented a difficult challenge to traditional practitioners. A patient might show severe anemia and easy tendency to bleed, the results of insufficient production of red blood cells and platelets. The high metabolism of the leukemic cells caused fever and fatigue. The patient might show swelling of internal organs as they are impacted by the large numbers of circulating white blood cells. The disorder would thus appear as a complex combination of deficiency and excess. The primary disease, buried in the bone marrow, might not have been easy to trace.

Along with Western diagnostics came the limited methods of therapy then available in the West; these included toxic treatments with arsenic compounds and, later, the introduction of some chemical agents, such as busulfan, which was, until recently, the standard treatment for myelogenous leukemia (it is of no value in other leukemias). The Western drugs that have been used for leukemia (including hydroxyurea, chlorambucil, and prednisone) appear in the modern Chinese medical literature as treatments given to control groups when evaluating Chinese therapies or used in integrated therapies.

Once the efforts of traditional Chinese doctors were turned to the problem of treating leukemia, it did not take long for certain antileukemic remedies to arise. According to Chang Zhinan of the Hematology Division of Capital Hospital in Beijing (3), leukemia (of modern diagnosis) has been subjected to various attempts at using Chinese materia medica items since about 1953. He reported that herbs have been applied for four purposes: reducing complications of leukemia, such as bleeding and infection; reducing adverse reactions to chemotherapy or increasing resistance of the body to adverse impact of leukemia; promoting the body's natural healing ability to reduce the impact and spread of the neoplastic process; and eradicating the leukemia cells. Today, there are basically three treatment methods: inhibit leukemia cells; promote the body function and protect it from leukemia and side effects of toxic treatments; and treat specific symptoms. These three will be analyzed below.

1. Inhibiting leukemia cells.

The primary traditional Materia Medica items for inhibiting leukemic cells have been indigo (qingdai) and realgar (xionghuang). Indigo is the purple dye obtained from certain plants, mainly Isatis tinctoria and Baphicacanthus cusia, but also from other Isatis species and from certain species of Clerodendron and Polygonum. This variability in source means that the market products can also have variable constituents and effects. The principal active constituent of indigo, in relation to leukemia, is indirubin, which was isolated and experimented with first by Western scientists and later investigated by Chinese researchers. Indirubin is a substance found in humans as well as in plants, possibly a metabolite of tryptophan. Indirubin levels in the urine are found to be increased in persons with various pathological conditions, including sprue, disturbed protein metabolism, renal diseases, myelocytic leukemia and other neoplasms (4).

Isolated indirubin is a drug product used in China. It is given in tablet form in dosages of just 150-200 mg each time (some patients receive a double dose), three times daily, for treatment of chronic granulocytic leukemia. It is reported that indirubin has better therapeutic effects, faster onset of effects, lower dosage requirements, and milder side effects than indigo. Side effects of indigo include abdominal pain, diarrhea, nausea, vomiting, and mushy stool. Almost all of these effects appear to be the consequence of an irritant action of the crude material and are dose dependent, though sensitivity to the irritant action varies widely among individuals.

While indirubin has a good effect on chronic granulocytic leukemia (this is the same type of leukemia that busulfan treats), it has a lesser effect on the non-granulocytic myelogenous leukemia and is not known to be effective for lymphocytic leukemia. Like other chemotherapeutic agents, indirubin has general bone-marrow suppressing action, but it is less than some antileukemia drugs, including busulfan.

Indirubin is not available in the West. However, Chinese immigrants to the U.S. have prescribed indigo (qingdai) in capsules to Western patients with leukemia who visit them. This herbal extract is not especially toxic, but, as mentioned above, it does easily produce gastric irritation that can limit the dosage to ineffective levels in some individuals. According to the author of Anticancer Medicinal Herbs (5) "Indigo really has an anticancer effect. The daily dose is 2-4 grams usually, but sometimes can be increased to 6-10 grams."

Realgar is a mineral compound that is mainly arsenic sulfide with some impurities. Arsenic inhibits leukemic cells. The use of arsenic in medicine was not limited to the Chinese, who have used it since ancient times to "cure debility and impotence and disperse accumulations." A drug dubbed "the first wonder drug of the twentieth century (6)," was Salvarsan, an arsenic compound that was found effective for treating syphilis (a disease previously treated by mercury compounds). Arsenic compounds are also used in Ayurvedic medicine. Realgar is listed in the modern Chinese Pharmacopoeia and is suggested to be used by making pills or powders, taken at a dosage of 150-300 mg each time, avoiding long-term administration. Realgar is sufficiently toxic that its use by Western practitioners is all but precluded; in fact, concerns for heavy metal contamination of Chinese herbs, especially with arsenic and mercury (mainly from realgar and cinnabar, included in many formulas) are so great that it would probably cause significant legal problems if someone were to knowingly prescribe this as a medicinal agent.

Other anticancer materials that the Chinese have used for leukemia include strychnos, camptotheca, cephalotaxus, celastrus, catharanthus, and toad secretion. These are all somewhat toxic and not used by Western practitioners. Cephalotaxus is related to the yew tree that yields the modern anticancer drug taxol; cephalotaxus has yielded the antileukemia drug harringtonine, which is extensively used in China, but not in the U.S. It is a treatment for acute monocytic leukemia (a type of AML). Camptotheca has been intensively studied in both the U.S. and China and yields the drug hydroxycamptothecin (used for acute myelocytic and lymphocytic leukemias), also not approved in the U.S. Strychnos, which contains strychnine, has anticancer properties but is not licensed for use here (it is an ingredient of the Chinese formula Ping Xiao Dan, used for many types of cancer). Celastrus contains dibromodulcitol, which is used to treat chronic granulocytic leukemia (same application as indigo). Catharanthus is the source of the standard chemotherapeutic agents vinblastine and leurocristine; these are used in treatment of ALL and AML.

Toad secretion contains bufotoxin, which is highly irritating and not permitted for use in the U.S. (one case of bufotoxin fatal poisoning was recorded in the U.S. recently when an herbalist accidentally filled a prescription incorrectly and substituted this item, it was present at a dosage much higher than would normally be used). Toad secretion also contains bufotenine, a compound similar in structure to indirubin. A well-known, but somewhat toxic patent medicine, Liu Shen Wan, is sometimes recommended by Chinese doctors for leukemia: it includes toad secretion and realgar. A toad secretion prescription, originally applied topically for treatment of lip cancer, was later used to treat ALL, with some success. It also includes realgar, as well as other toxic materials, such as cinnabar and calomel (both contain mercury).

These Chinese leukemia remedies have the same function as modern pharmacological interventions that we call chemotherapy. In fact, Chinese chemotherapy is sometimes simply derived from herbal active constituents, including harringtonine, indirubin, and hydroxycamptothecin. The purpose is to inhibit the abnormal bone marrow cells, so as to permit the growth and function of the normal cells. In China, there are more of these drugs available than in the U.S. as the result of fewer restrictions on drug licensing.

Anti-CML Pill

The discovery that indigo was clinically effective for leukemia was made in the early 1960's, when researchers at the Institute of Hematology, Chinese Academy of Sciences (Beijing) noted that an herbal formula prescribed by Chinese doctors appeared to be producing good results in many patients. The formula, Danggui Luhui Wan, included indigo as an ingredient and had prominent action in cases of chronic myelocytic leukemia (CML). The formula also contains tang-kuei, gentiana, coptis, phellodendron, scute, rhubarb, aloe, saussurea, and musk, and was traditionally used for reducing fever, purging intense heat, and removing toxin. A modified version of the traditional formula, which includes both indigo and realgar, was developed at this Institute, and reported to be even more effective than the original: it was called the anti-CML pill. It contains indigo, realgar, ranunculus, sophora, scute, phellodendron, tang-kuei, terminalia, leech, and eupolyphaga.

The basis for adding realgar to the indigo was that potassium arsenite, a related compound, had previously been used for treating CML by Western-style practitioners (in the 1940s), but had been abandoned due to toxicity problems. The lower toxicity of realgar may be due solely to differences in rates of absorption from the intestinal tract. Realgar was substituted for potassium arsenite and reported effective in 1960 by a hospital in Shanghai. It was found in one small study in 1970 that complete remission could be attained in some leukemia patients by administering 9-18 grams of realgar per day (by decocting it, where only a fraction is solubilized; usual dosages of orally ingested powder are less than 2 grams per day). The adverse effects were less than those of potassium arsenite. Another toxic arsenic compound formula, made with arsenic oxide, was reported by a group in Harbin to be reasonably effective for acute myelocytic leukemia. According to the author of Anticancer Medicinal Plants, realgar is also single remedy for chronic granulocytic leukemia, taken at a dose of 0.3-0.9 grams each time, one or two times daily.

Indigo had been tested as a single herb remedy for CML in the 1970s. A dose of 6-12 grams per day was reported to achieve complete or partial remission. The remission rate increased when realgar was added as 11% of the formula (for example: 1 gram realgar mixed with 8 grams indigo). Recent treatments in China continued to rely on the crude material for some time, even though indirubin is available. As an example, Qinghuang Powder, prescribed at the Xiyuan Hospital for treating chronic granulocytic leukemia, is made of a 9:1 ratio of indigo and realgar, given in capsule form, with a daily dosage of 6-14 grams, divided into three doses; a maintenance dosage, after improvement is attained, is 3-6 grams per day.

The anti-CML pill is reported, by the group that worked with it, to be more effective than indigo-realgar treatment alone. The reason for this is not yet established. Other ingredients in the pill include sophora root (which contains the anticancer ingredient matrine) and tang-kuei, which may serve in a protective role. Arsenic levels of patients taking this pill were monitored by urine analysis. Chronic arsenic intoxication produces changes in the skin, with pruritis, skin pigmentation, and keratodermia, and it may cause mild peripheral neuritis. If such occurred, arsenic was cleared from the system using sodium dimercaptopropan sulfonate or sodium dimercaptosuccinate. By simply stopping the use of the anti-CML pill, urinary excretion of arsenic would reduce over a period of 1-6 months. The researchers working with the anti-CML pill felt that the problem of arsenic toxicity was manageable.

In the U.S., the only one of the specific anti-leukemic substances that can be reasonably prescribed is indigo (qingdai). When Chinese immigrant doctors have prescribed encapsulated indigo to their patients it is usually administered at doses far lower than the 6-12 grams reported above (typical amounts are 1-3 grams).

Patient Improvements with Treatment

Remission rates described in the clinical reports from China may be easily misinterpreted. A remission in the case of leukemia means that there is a dramatic reduction in the levels of the affected white cell line, accompanied by improvements in the impaired cell lines and in symptoms. Complete remission means normalization of the blood picture, while partial remission means improvement without attaining normal condition of blood cells. However, some time after this remission has been observed, the disease usually recurs. For example, in a study of bufotoxin treatment of acute leukemia, it was reported that partial remission was attained in 50% of patients and full remission was attained in 25% of patients. The longest remission period was 6 years. In a study of 6 patients treated with realgar plus indigo, it was reported that complete remissions occurred in 3 patients; and 2 of those patients lived more than four years.

Remission usually results in a period of a few months or years free of the cancer; when the leukemic condition returns, one must start treatment again, usually in the midst of a blast crisis. Producing a remission and then extending the remission period is the goal of current treatments. In one study comparing busulfan with alternating busulfan and anti-CML pill, mean survival time was reportedly increased from 40 months to 61 months. The same results were reported in another comparative trial with busulfan alone versus alternating treatment with busulfan and an herbal pill, similar to the anti-CML pill, called Manli Wan (composed of ranunculus, sophora, scute, phellodendron, tang-kuei, terminalia, indigo, eupolyphaga, and leech). These alternating strategies are deemed interesting to Western-trained Chinese doctors because the busulfan is so toxic.

In a long-term study of indirubin treatment for CML, it was reported that "maintenance therapy [with indirubin] was necessary for CML patients after achieving complete remission and there was no obvious side effects over long-term administration of the drug. Unfortunately, indirubin could not suspend or postpone development of blastic crisis (7)." Median survival time in this study of 57 cases of CML treated with the simple protocol of indirubin administration was 31.5 months. Put simply, remission of leukemia is usually a temporary condition.

Improvement in the quality of life of patients is also a major factor, despite any changes in blood picture or duration of life. The proponents of Chinese medicine suggest that rates of complete and partial remission and quality of life are improved by using Chinese medicine, but the duration of survival may increase only slightly (by a few months), if at all. About 20% of chronic leukemia patients can attain survival times of 10 years or more.

2. Complementary medical approach

Chinese doctors have worked out strategies of complementing the basic anti-leukemic approach, whether the modern chemotherapy or the traditional style (e.g., realgar and indigo) are used. These complementary approaches often involve non-toxic herbs that could be prescribed by practitioners in the West; but there are also toxic substances mentioned in the literature for this purpose. For example, in the book Anticancer Medicinal Herbs, it is reported that the toxic insect mylabris, when accompanied by chemotherapy, can control leukopenia in patients with leukemia. Since a major problem with mylabris is its irritant effect, the Chinese pharmaceutical factories have added mung bean flour to the preparation of tablets, which protects the gastro-intestinal tract from irritation.

In the book Treatment of Cancer with Fu Zheng Pei Ben Principle (8), this is said:

Leukemia is a disease of constitutional dimensions and, as such, its treatment should be comprehensive: eliminate and inhibit the hyperplastic leukemia cells, and at the same time protect the integrity of the normal tissues. The crucial point when treating this disease is a comprehensive therapeutic approach which can deal properly with the delicate relationship between dispelling pathogenic factors, while restoring normal functions of the body....A very large number of clinic experiences and recordings show conclusively that a course of treatment combining the principles of TCM and western medicine is always better than either one applied alone. Effectiveness of chemotherapy can be greatly enhanced when supplemented by TCM based on principles of syndrome differentiation. The regulatory and stabilizing effect of TCM administered during respite between chemotherapy cycles helps maintain the efficacy of the original treatment and prolongs the period of remission.

A sample treatment for acute leukemia (AML) presented in this book is a modified Rhino and Rehmannia Decoction (Xijiao Dihuang Tang), which includes raw rehmannia, moutan, rhino horn (substituted by water buffalo horn), lithospermum, lonicera, isatis leaf, indigo (12 grams), scrophularia, gypsum, and lycium bark to clear heat and toxin, with turtle, tortoise shell, and pseudostellaria to nourish yin. It also contains some blood-vitalizing herbs (red peony, agrimony, and carthamus). This treatment is to be applied to cases of high fever and sweating, spontaneous bleeding, and other symptoms that are characteristic of uncontrolled leukemia. The ingredients can be understood in terms of presenting symptoms: lithospermum, raw, rehmannia, and rhino horn, for example, are used for high fever and spontaneous bleeding; turtle shell and tortoise shell not only nourish the blood and yin, but also prevent hemorrhage. The anti-leukemic substance, indigo, is provided in the highest quantity usually recommended.

The difficulty with this approach is that the very high dosage decoction (over 200 grams per day) would have an extremely bitter taste and would likely have an irritating and even an inhibiting effect on the digestive system (which is probably already weakened by the disease and prior treatments). Therefore, one would hope to use a different prescription, such as the others offered in that book and described below.

A common complaint of leukemia patients is chronic low grade fever and fatigue. This is the combined result of deficient blood status, side effects of cancer therapies, and secondary effects of continuing leukemia (especially the high metabolic status of the white blood cells). A recommended treatment is to use 24 grams of salvia, 20 grams millettia, 20 grams agrimony and 6-15 grams each of the following: ginseng, red peony, tang-kuei, cnidium, persica, astragalus, hoelen, atractylodes, licorice, and pseudostellaria. This formula nourishes qi and blood and vitalizes blood circulation. It is to be used in conjunction with chemotherapy to enhance its effects and alleviate the characteristic symptoms the patient faces. This formulation, although high in dosage, has a tolerable taste and is unlikely to cause gastro-intestinal irritation; to the contrary, it has herbs that may improve the condition of the gastro-intestinal system. Other complementary formulas for leukemia recommended in this book focus more on tonic actions, by combining yin tonics (for those showing more evident signs of yin deficiency) or tonics for the qi and essence (for those showing overall deficiency syndrome).

The formulas for leukemia patients do not differ significantly from those that might be used in various types of cancers in which the patient is receiving chemotherapy. That is, the fact that leukemia is being treated does not strongly influence the selection of herbs or formulations. The patient ought to be evaluated for evidence of the common problems of blood stasis, yin deficiency, qi deficiency, essence deficiency, organ swelling, etc., and treated accordingly. In each case, a total daily dosage of about 200 grams is recommended in this book. These dosages are impractical for American patients, who are not used to taking such decoctions. Even when using dried decoctions, a total daily dosage of 30 grams of the powders (corresponding to about 150 grams of crude herbs in decoction) is usually deemed too much. However, a lower total dosage might be successfully used if a smaller number of herbs are selected and if they closely match the Oriental diagnosis of patient requirements.

In some of the Chinese reports on treating leukemia patients, general anticancer herbs that are non-toxic or of low toxicity, such as scutellaria, oldenlandia, solanum (lyratum or nigrum), and paris, are included in the formulas. It is not known at this time whether these have a specific antileukemic effect.

3. Treating specific symptoms of leukemia

Chinese physicians apply herbs according to traditional principles to treat certain characteristic symptoms of leukemia. These include (9):

  1. Anemia: treated with herbs that nourish the blood, including marrow-nourishing agents. Examples are tang-kuei, cnidium, peony, rehmannia, lycium fruit, deer antler, epimedium, codonopsis.
  2. Hemorrhage: treated with hemostatic herbs. Examples are raw tien-chi ginseng, agrimony, and cirsium.
  3. Fever: treated with herbs that cool heat and nourish yin. Examples are raw rehmannia, moutan, scrophularia.
  4. Swelling of the liver, spleen, lymph nodes, etc.: treated with herbs that resolve masses. Examples are laminaria, sargassum, oyster shell, curcuma, chih-ko (or other citrus materials), pangolin scales.
  5. Ulceration and swelling of the gums, tongue, and oral cavity: treated with herbs that alleviate aphthae, such as fire-purging agents. Examples are coptis, gardenia, raw licorice, borneol.
  6. Skin eruptions and purple maculae: treated with herbs that promote blood circulation and clean toxins. Examples are red peony, dandelion, carthamus, salvia, lonicera.
  7. Aching: treated by herbs that regulate qi and blood and analgesic herbs. Examples are corydalis, pteropus, typha, cyperus, lindera, sandalwood.

In each of the cases, these agents are selected according to standard principles of Oriental diagnostics and prescribing, with no special reference to the source of the symptoms as being leukemia.

One can see from untreated cases that this disease would be diagnosed as a syndrome involving pathogenic heat in the blood. Such a condition would help to explain several symptoms, such as fevers, bleeding (and appearance of purple maculae), skin eruptions, and ulceration and swelling in the oral cavity. Not surprisingly, the traditional remedies are often based on formulas for such symptoms that might arise as well from other causes. The Rhino and Rehmannia Combination is one such formula. The traditional formulas can be modified by adding one or more blood tonics to address the anemia, and one or more herbs for dispersing accumulations to treat the organ swelling and accompanying aching. The Danggui Luhui Wan formula, that includes indigo and was at the basis of the anti-CML pill, is an example; it contains saussurea, rhubarb, aloe, and musk to help get rid of accumulations.

Examples of Current Chinese Treatment Strategy for Chronic Leukemia

In a recently published clinical trial (13), patients with chronic granulocytic leukemia (a type of CML) were treated with herbs according to syndrome differentiation, mainly in the categories of qi/blood deficiency, liver/kidney deficiency, or blood stasis. Details given were sketchy, but all patients received the anticancer herbs scutellaria, oldenlandia, and lasiosphera (puff-ball mushroom, most often used to treat lung ailments), and the tonic herbs codonopsis and peony, along with herbs that were specific for the syndrome (examples: tang-kuei and astragalus for qi/blood deficiency; rehmannia and ophiopogon for liver/kidney deficiency; sparganium and zedoaria for blood stasis).

If the pathological condition became serious during the treatment period (or was quite serious at the outset), chemotherapy was also used. Either busulfan or hydroxyurea was given for this purpose. Other herbs or drugs could be given to treat specific symptoms, such as infections, bleeding, or severe anemia.

The short term results indicated that after six months of treatment, 69% of patients had complete remission, 25% had partial remission, and only 6% did not respond. Treatment continued beyond six months. The ultimate results of therapy were measured in terms of survival time from initial diagnosis. Of 80 patients, 37 lived less than 3 years, 16 lived 3-4 years, and the remaining 27 patients lived for 5 or more years. The median survival time was 3.8 years.

While the remission rates reported in this article are quite good, the survival rates are not significantly better than those reported in the U.S. where indirubin and complementary Chinese herb therapies have not been used. However, it is possible that the clinic was presented with more severe cases of leukemia to treat. In some earlier studies, median survival times of 5 years were reported.

In another trial of indirubin plus herbs for chronic granulocytic leukemia (14), patients were treated by indirubin, 50 mg each time, 3 times daily. Herbs given according to syndrome differentiation:

  1. Qi Stagnation with Liver/Spleen Enlargement: ching-hao, lycium bark, red peony, moutan, sparganium, zedoaria, salvia, solanum lyratum, oldenlandia, cremastra, turtle shell, tortoise shell, gardenia, chih-ko, rhubarb, licorice (each item, 9-15 grams, except 30 grams oldenlandia). Note that solanum, oldenlandia, and cremastra are general anti-cancer herbs.
  2. Qi and Yin Deficiency: pseudostellaria, asparagus, rehmannia, ching-hao, lycium bark, oldenlandia, solanum nigrum, scutellaria, eclipta, lycium fruit, turtle shell, sophora subprostrata, forsythia, lonicera stem, gallus, baked licorice (each item, 9-15 grams, except 30 grams oldenlandia). In this formula, oldenlandia, solanum, scutellaria, and sophora subprostrata are general anti-cancer herbs.

Complete remission was attained in 40% of the patients, partial remission in 50%, no benefit in 10%. About 15 days of treatment were required to reduce spleen enlargement, with normalization after about 40 days. Leukocyte levels began to show decline after about 10 days, with 60 days treatment required to get to the normal range in responsive patients. Long-term results were not reported. This study reveals that one can monitor the effectiveness of the treatment by checking leukocyte levels over a two month period.

Recommendations for Western Practitioners

Patients with leukemia, especially with chronic leukemia that is the most likely syndrome to be presented to practitioners of Chinese medicine, are often depressed and debilitated when they present themselves for treatment. The depression may result from having a diagnosis of cancer, especially with a poor prognosis, and from any failures up to this point in gaining an adequate resolution. The debility may result from the effects of the disease and/or treatments that have been tried thus far; also, chronic leukemia is usually seen in older individuals, who may experience debility from poor nutritional habits, lack of exercise, and other characteristics common to elderly persons with chronic disease. Leukemia may arise at this time of life from insufficient immune functions, lack of antioxidant activity, and stresses that permit chronic viruses to activate.

The first thing a practitioner can do is assure the patient that the poor prognosis of the disease may be improved by nutrition and herbal therapy. Although there are a number of clinical reports from China that describe disease remission (and improved rates of remission compared to using chemotherapy alone), one should be cautious about promising too much from the treatments to be offered. There is reasonable evidence from China that leukemia patients can get symptomatic relief and may have prolonged life span (perhaps 50% longer than that normally expected with standard chemotherapy) by the use of herbs and improved nutrition.

Patients should be directed to consult with their oncologist(s) to get a clear picture of the prognosis that is expected with a chemotherapeutic or other intervention that is currently being undertaken or might be pursued. Both the risks and benefits of the chemotherapy course should be weighed. If the prognosis is not very good and the adverse effects are troubling, then one might pursue a course of natural therapies only, with the knowledge that the prognosis (in terms of survival time) is not necessarily improved but the adverse effects of chemotherapy might be avoided. If the prognosis is good, then a combined therapy, using Chinese herbs and nutrition in a supportive role might be a valuable course of action. Some oncologists might even be willing to entertain a program of alternating chemotherapy and herbal therapy for patients who are not open to using the standard chemotherapy.

When there has been chemotherapy failure or when there is refusal to use chemotherapy, a treatment similar to the anti-CML pill may be of value for myologenous leukemias. This approach usually relies on the use of indigo as the primary therapy, with various supporting herbs to be included in the treatment, probably in the form of dried decoctions (formula designed by the practitioner), or, if the patient is unwilling to use that method, tableted formulas (in large quantities). A monthly blood draw can be used to monitor the progress of the treatment, along with the standard examination of symptom changes.

Indigo can be provided in capsules, starting at a dose of about 1 gram per day and working up to 6 grams per day, or up to tolerance levels. Once the maximum level has been determined, herbal combinations should likewise be administered starting at a modest dosage and working up to a maximum possible dosage. For example: using decoctions, begin at 30 grams per day; using dried decoctions, start at 6 grams per day, using tableted formulas, start at 9 tablets per day. Let the patient know about the high dosage form of natural materials. The ability to ingest and tolerate large amounts of herbs (and, possibly, nutritional supplements) may be a key to success with this natural approach.

It has been reported that indirubin used for an extended period of time may cause pulmonary hypertension and cardiac insufficiency in some patients (10). This effect, which occurred in persons treated for 9 months to 3 years, was slowly reversed when the indirubin was removed. Presumably, this adverse reaction could occur with administration of the higher doses of natural indigo, as it contains indirubin. Therefore, any patients who are to be treated for 9 months or longer should have their cardiac function monitored.

While specific nutritional approaches have not been developed for leukemia, certain general methods can be applied:

  1. Make sure the individual is receiving adequate basic dietary nutrients, such as proteins, fats (preferably unsaturated), and carbohydrates. Monitor body weight and muscle strength, and take further action if there is not improvement, including recommending easy-to-use concentrated nutrition sources.
  2. Provide additional nutrients and a high level of antioxidants using supplements (11). General anticancer substances may be tried, including flavonoids (quercetin, genestein, tea polyphenols), minerals (selenium), and vitamins (high dose vitamins A, C, and E). Even if these fail to produce a cancer-inhibiting action, they may provide other benefits for persons in the age group that suffers from chronic leukemia.
  3. When possible, use Oriental dietary techniques to match the dietary components to the symptom/sign pattern (12). For example, use cooling foods for fevers, astringent foods for sweating, yin-nourishing foods for yin deficiency patterns, etc. Make sure the suggestions include using foods that can reasonably be obtained and prepared.

The relative deficiency of reports in the Chinese literature regarding treatment of chronic lymphocytic leukemia (CLL) with herbs is mainly due to the fact that CLL is very rare in the Orient, due to genetic factors. Although a few recipes for treatment (based on traditional principles for treating the symptom presentation) have been published, evidence for their effectiveness is lacking because of insufficient case studies. The approach to be taken would be to treat according to the traditional syndrome differentiation, in combination with standard chemotherapy when possible. Chronic granulocytic leukemia appears to be the type of leukemia most intensively investigated, no doubt as a response to early findings of benefit from using traditional Chinese herbal materials coupled with a relatively high frequency of incidence in China. Acute leukemia is always treated with a chemotherapy, with reported improvements attained by adding Chinese herbal therapies.

APPENDIX: Treatment Strategies for Acute Leukemia

In the book An Illustrated Guide to Antineoplastic Chinese Herbal Medicine (18), the following formulas for acute leukemias are relayed from the medical literature during the period 1981-1985:

Toad Skin Wine: 1.8 kg toad, with viscera discarded, in 1.5 liters wine; dosage of 15-30 ml three times per day after meals, for various kinds of leukemia, especially ALL.

An Lu San: made of centipede, scorpion, silkworm, and eupolyphaga (in equal amounts, ground to powder, administer 0.3-1.0 grams each time, three times daily) for all acute leukemias.

Anti-leukemic mixture: with lonicera, rhaponticum, scutellaria, dandelion, viola, millettia, cuscuta, salvia, epimedium, coptis, prepared as a decoction 6-10 grams of each herb (except coptis, 3 grams), administer 25 ml each time, twice daily. When acute crisis is relieved, make a pill using deer antler as the main ingredient, plus ginseng, peony, rehmannia, ho-shou-wu, lycium fruit, zizyphus, salvia, epimedium schizandra, tang-kuei, astragalus, sesame oil, carthamus, cnidium, and a small amount of realgar (1.5%). Administer the pill (with about 130 mg herb ingredients) twice daily for maintenance. This treatment is indicated for acute leukemia in children (probably for ALL).

Oldenlandia Decoction: with oldenlandia, isatis root, solanum lyratum, trichosanthes fruit, paris, lithospermum, and belamcanda. Each ingredient is 15-30 grams, except belamcanda 9 grams. Used for acute leukemias.

Acute Leukemia Decoction: with rehmannia, hoelen, astragalus, oldenlandia, solanum nigrum, sophora subprostrata, lithospermum, dioscorea, cornus, cistanche, morinda, psoralea, ginseng, ophiopogon, schizandra, tang-kuei (each ingredient 10-30 grams, except tang-kuei, 6 grams), indicated for non-lymphocytic leukemia, as an adjunct to chemotherapy.

Anti-Cancer Formula 7: with oldenlandia (75 grams), solanum nigrum (60 grams), coix (60 grams), san-chi (9 grams), dioscorea bulbifera (6 grams), and mume (6 grams), indicated for acute granulocytic leukemia.

Toad Skin and Scutellaria Decoction: with toad skin, scutellaria, isatis root, rhubarb, solanum lyratum, paris, lithospermum, and belamcanda; all ingredients 15-30 grams, except toad skin (9-12 grams, and belamcanda 9 grams). Indicated for acute granulocytic leukemia as a supplement to chemotherapy.

In a study of acute leukemia patients (15), 18 cases were treated with Chinese herbs plus chemotherapy and 21 cases were treated with chemotherapy alone. The herbal therapy, in the form of decoction, was comprised mainly of tang-kuei, cnidium, millettia, red peony, carthamus, and san-chi. The treatment group had a higher percentage of cases gaining remission (89% vs. 57%) and a longer mean survival time (13 months vs. 7 months).

Another study (16) involved 70 acute leukemia patients divided randomly into two groups, one receiving chemotherapy alone and the other receiving chemotherapy plus herbs in decoction. Those receiving herbs were divided into three groups according to syndrome:

  1. Excess heat type: lonicera, forsythia, isatis leaf, dandelion, oldenlandia, scutellaria, sophora subprostrata, isatis root, buffalo horn, scrophularia, rehmannia, red peony, lithospermum, and imperata, all herbs in heavy dosage (15-30 grams); if there was liver spleen enlargement, there was also added 15 grams each of salvia, sparganium, and zedoaria.
  2. Qi and yin deficiency type: pseudostellaria, astragalus, atractylodes, lycium fruit, hoelen, polygonatum, asparagus, ophiopogon, scrophularia, ligustrum, eclipta, dandelion, scutellaria, oldenlandia, and cirsium, all in heavy dosage of 10-30 grams.
  3. Qi and blood deficiency type: astragalus, codonopsis, atractylodes, hoelen, tang-kuei, gelatin, lycium fruit, psoralea, ho-shou-wu, oldenlandia, cirsium, salvia, and millettia, all in heavy dosage of 15-30 grams.

The Western medical treatments were also differentiated according to whether the disease was the acute lymphocytic type, acute non-lymphocytic type, or acute granulocytic type.

Of 35 patients in the integrated therapy group, 69% had complete remission and 20% had partial remission, with 11% not improved; of 35 patients in the Western medicine group 43% had complete remission, and 20% had partial remission, with 37% not improved. Survival time was reported to be longer in the integrated group than the partial remission group, but the details in the report were unclear.

An article (17) describing treatment of a small number of patients with refractory recurrent acute leukemia, indicated that those who failed to attain remission by chemotherapy alone could sometimes gain benefit from combined therapy with Chinese herbs. Sixteen patients were treated according to syndrome differentiation, all having internal pathogenic heat, with four subtypes: qi and yin deficiency; damp-heat plus blood stasis; phlegm nodules; blood stasis with movable mass. In each case, a decoction was given to address the syndrome. It was reported that 10 of the patients had complete remission, and 2 patients had partial remission as a result of using 1-4 months of therapy, an average of 3 months.


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  4. Hson-Mou Chang and Paul Pui-Hay But (eds.), Pharmacology and Applications of Chinese Materia Medica, (2 vols.), 1986 World Scientific, Singapore.
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  7. Qian Linsheng, et al., "Observation on the long period effect of indirubin in the treatment of 57 cases of chronic myelogenous leukemia," Chinese Journal of Hematology 1991; 12(3): 125-127.
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  9. Sun Chiyuan, A Probing into the Treatment of Leukemia with Traditional Chinese Medicine, 1990 Hai Feng Publishing Company, Hong Kong.
  10. Jiang Shuzhen, Yu Gong, and Cao Jinni, "Adverse effect of indirubin on the cardiovascular system, a report of 3 cases," Chinese Journal of Hematology 1986; 7(1): 30.
  11. Werbach M, Nutritional Influences on Illness, 1993 Third Line Press, Tarzana, CA.
  12. Lu HC, Chinese System of Food Cures, 1986 Sterling Publishing Co. Inc., New York, NY.
  13. Tao Shuchun, "Observation on clinical effect of 80 cases of chronic granulocytic leukemia treated with Chinese medicine mainly," Journal of Traditional Chinese Medicine, 1997 38(6): 349-350.
  14. Yin Pingping, "Observation on clinical effect of 20 cases of chronic granulocytic leukemia," Shanghai Journal of Traditional Chinese Medicine 1997; (6): 31.
  15. Deng Youan, et al., "Additional use of blood-activating Chinese herbs in chemotherapy of acute leukemia," Sanxi Medical Journal 1988; 17(2): 79-81.
  16. Yan Yi, "Analysis of therapeutic effectiveness in 35 cases of acute leukemia with therapy by Chinese integrated medicine," Chinese Journal of Integrated Traditional Chinese and Western Medicine 1995; 15 (1): 643-645.
  17. Wang Jiliang, "Clinical research on treatment of 16 patients with refractory recurrent acute leukemia," Practical Journal Integrating Chinese and Modern Medicine 1996; 9(3): 138.
  18. Ou Ming, et al., An Illustrated Guide to Antineoplastic Chinese Herbal Medicine, 1990 Commercial Press, Hong Kong.

Bibliography for Further Examples of Herb Therapies Used for Leukemia

Cheung CS, et al., translators, "Leukemia-Understanding and treatments in traditional Chinese medicine," Journal of the American College of Traditional Chinese Medicine 1982; (1): 73-85. [translation of Chinese report by the Hematology Group of Xiyuan Hospital in Beijing, originally published 1976, just prior to introduction of indigo-based treatments for leukemia]

Jia Kun, Prevention and Treatment of Carcinoma with Traditional Chinese Medicine, 1985 Commercial Press, Hong Kong. [includes a chapter about using Ping Xiao Dan plus other therapies to treat leukemia].

Shi Lanling and Shi Peiquan, Experience in Treating Carcinomas with Traditional Chinese Medicine, 1992 Shandong Science and Technology Press, Shandong. [this book has a section on leukemia that simply lists several "proved recipes," that is, formulas that appeared in journal articles or books with case presentations illustrating positive results]

December 1997