Clinical Observation on Treatment of Acute Non Lymphocytic Leukemia with Agaricus Blazei Murrill

by:
Drs. Tian Xiao Hui/Lun Zheng Guo/Wang Jing – Department of Hematology, The First Affiliated Hospital of Lanzhou Medical College, Drs. Hitoshi Ito/Keishiro Shimura/Wang Jun Zhi – Mie University School of Medicine

Overview

Ten cases of acute non-lymphocytic leukemia (ANLL) were treated with chemotherapy using Agaricus Blazei. The results showed that Agaricus Blazei could promote the bone marrow hemopoiesis in vivo, improve bone marrow inhibition after chemotherapy and remarkably increase the concentration of Hb, the number of Wbc and Plt in peripheral blood (P<005-0.02). It also enhanced the concentration of lgM (P<0.05), albumin and A/G ratio and decreased the concentration of globulin in plasma (P<0.01-0.05). It indicated that Agaricus Blazei could promote liquid immune function and had some inhibitory effects on leukemia cells in ANLL patients. No side effects were found in the treatment of Agaricus Blazei. The method is safe and remains to be further studied and applied.

(Keywords: Agaricus Blazei, Acute Non-Lymphocytic Leukemia (ANLL), Clinical Treatment)

Agaricus Blazei is a fruit body of fungi plant. As shown in the experiments and researches by Japanese academics, its hot water extract (includes water-soluble polysaccharides as a main component) has effects such as immunological enhancement and tumor growth inhibition. In animal experiments conducted in China, it was found that the polysaccharides extracted from Agaricus Blazei (ABPS) promote the proliferation of CFU-S, CFU-GM, CFU-E and CFU-F of rats. In order to make a progress in its clinical research and application perspectives, we carried out a clinical observation of 10 examples of acute nonlymphocytic leukemia patients under treatment with Agaricus Blazei from July 1992 to May 1994, which we report as follows:

Material and Method

I. Selection of Patients

The subject 20 examples were the patients with acute nonlymphocytic leukemia who received initial treatment at the Department of Hematology, The First Affiliated Hospital of Lanzhou Medical College. All examples comply with the diagnosis standard for acute nonlymphocytic leukemia established by Tientsin Leukemia Classification Conference held in September 1986. The patients were randomly divided into experimental and control groups, each consisting of 10 patients. There is no obvious difference between the two groups as to their age, the length of period with disease, condition (symptoms and signs), and chemotherapy that they had been receiving.

The experimental group consisted of 6 males and 4 females (2 x M₂, 2 x M₃, 1 x M₄ and 5 x M₅). Their age ranged 22 - 58 and the average was 34.1.

The control group consisted of 8 males and 2 females (1 x M₁, 1 x M₂, 1 x M₃, 4 x M₄, 3 x M₅). Their age ranged 23 – 55 and the average was 36.4.

II. Treatment Method

The experimental group was treat under chemotherapy of standard induction and remission method including "daunorubicin + cytarabine" method with 14 – 21 days of intermittence period. The chemotherapy was given 3 times during the period they took medicine made with Agaricus Blazei. After the first treatment using hot water extract of Agaricus Blazei (supplied from Iwakin Co., Ltd. Laboratory of Japan), the daily amount was increased to 20g (twice a day). The patients took the medicine for total 3 months.

The control group patients received the chemotherapy and conditional support, but did not take the medicine made from Agaricus Blazei.

III. Monitored Values

1. Clinical Symptoms and Signs:

Mental condition, appetite, nausea, blood pressure, etc.

2. Laboratory Tests

2.1 Changes in Blood Picture

2.2 Changes in Bone Marrow Picture

2.3 Various items of biochemical blood tests including plasmatic protein, immunoglobulin, serum iron metabolism, liver and renal functions.

3. Infection:

The number of infected patients and infected parts of body were monitored.

4. Side Effect:

Patients went through rigid inspection during and after treatment for any side effects.

5. Statistical Processing:

“T” inspection processing was applied to the data of each item.

Result

1. Influence of Agaricus Blazei to the Blood Picture of Acute Nonlymphocytic Leukemia Patients:

As shown in the experiment result, peripheral blood hemoglobin, platelets and leukocyte remarkably increase after treatment with Agaricus Blazei (see Table 1).

2. Influence of Agaricus Blazei to the Bone Marrow Picture of Acute Nonlymphocytic Leukemia Patients:

Table 1: Influence of Agaricus Blazei to the Blood Picture of Acute Nonlymphocytic Leukemia Patients (x±S)

Note: * Comparison within the group
** Comparison with the result of control group patients after treatment

Among the 10 patients of the experimental group, 8 patients reached complete remission (CR) and 2 patients remained with no remission (NR). The bone marrow pressure time after the chemotherapy was short. Bone marrow proliferation, ratio between red, granule and large nucleus cells recovered the normal level within 7 – 8 days from the end of chemotherapy.

On the other hand, among the 10 patients of the control group, 5 patients reached CR, 2 patients reached partial remission (PR) and 3 patients remained with NR. The bone marrow pressure time after the chemotherapy was long. 8 patients recovered the normal level 14 – 21 days after chemotherapy and 2 patients remained abnormal.

3. Influence of Agaricus Blazei to Total Protein, Globulin, Albumin and A/G ratio of Acute Nonlymphocytic Leukemia Patients:

Plasmatic albumin of the experimental group patients obviously increased and globulin decreased, resulting in increased A/G ratio. Plasmatic total protein, albumin and globulin of the control group patients showed no change (see Table 2).

Table 2: Influence of Agaricus Blazei to the Total Protein, Globulin, Albumin and A/G Ratio of Acute Nonlymphocytic Leukemia Patients (x±S)

Note: * Comparison within the group
** Comparison with the result of control group patients after treatment

4. Influence of a Agaricus Blazei to the Immunoglobulin of Acute Nonlymphocytic Leukemia Patient

As shown in the experiment result, lgM of the experimental group patients obviously increased, while lgG and lgA remained close to those of the control group patients (see Table 3).

Table 3: Influence of Agaricus Blazei to the Immunoglobulin of Acute Nonlymphocytic Leukemia Patients (x±S)

Note: * Comparison within the group
** Comparison with the result of control group patients after treatment

5. Symptoms and Signs

Mental condition and appetite of the experimental group patients were remarkably improved. Obvious recovery in symptoms including fatigue, dizziness, nausea of 8 patients was reported. The experimental group suffered fewer side effects compared to the control group.

6. Infection

Compared to the control group, far less number of experimental patients were found to have been infected and the level of infection was lower. The number of patients with infections (pulmonary, pharyngolaryngeal, intestinal) totaled 6 in the experimental group and 13 in the control group.

7. Side Effect

No adverse effect was observed during the administration period of Agaricus Blazei.

Discussion

Scholars in Japan are making researches on Agaricus Blazei in its aspects such as pharmaceutical components, structural characteristics and active elements. Agaricus Blazei, as shown in their studies, has effects to enhance immunity system and inhibit tumor growth. Researches in China discloses that the polysaccharides extracted from Agaricus Blazei promote the proliferation of bone marrow multifunction hematopoietic cells, simple granule cells, red cells and fibroblasts of a normal rat. However, no report on its clinical application to leukemia patients has been released yet.

With the understanding of the said effects and mechanism, we observed the influence of Agaricus Blazei to leukemia patients based on chemotherapy. As a result of clinical research, it was confirmed that Agaricus Blazei promotes the hematopoiesis by the bone marrow. Direct reactions in the bodies of acute nonlymphocytic leukemia patients include short bone marrow pressure period, early hematopoietic restoration by the bone marrow and fast recovery of granule, red and large nucleus cells to normal level. Indirect reactions include remarkable improvement in peripheral blood picture and obvious increase of total number of hemoglobin, platelets and leukocyte, which is remarkable compared to control group after therapy (P<0.005 - 0.02). Myelopoiesis promoted by Agaricus Blazei apparently improves the condition of myelopoiesis pressure and promotes the restoration of peripheral blood picture of leukemia patients under chemotherapy. This is achieved to the same degree as the result of “Observation on Treatment Effect of Agaricus Blazei against Alimentary Tract Tumor”.

Various vegetable polysaccharide components extracted from Ganoderma Lucidum, Polyporus Umbellatus, etc. are effective in immunological enhancement and promote antitumor activity. By comparing before and after the treatment period in our experiment, we found the lgM value of experimental group patients obviously increased (P<0.05) while lgG and lgA remained at the same normal level as those of control group (P<0.05 – 0.1). Hence, Agaricus Blazei is conceived to have an effect to improve the restoration of damaged immunity function and promotes the reinforcement of humoral immunity function. As shown in the research by Lee Hai Qian et al., Agaricus Blazei also promotes the reinforcement of internal cellar immunity function. This is considered to have been achieved by activation of immunity system through the antitumor effect of Agaricus Blazei.

The experimental group patients were checked after treatment and were found to have obviously increased plasmatic albumin and decreased globulin, resulting in obviously higher A/G ratio. On the other hand, these values of control group patients did not obviously change during the treatment (P>0.05-0.1). Since no damage in liver function was observed for both groups during the treatment, the change in plasmatic protein of the acute leukemia patients can be considered as a result of certain action by Agaricus Blazei against tumorous cells and not due to change in liver function. However, further study will be necessary to determine if the action was achieved directly by Agaricus Blazei or indirectly through reinforced internal immunity activation.

In short, Agaricus Blazei demonstrates its clinical effectiveness against acute nonlymphocytic leukemia through such effects as promotion of myelopoiesis, improvement of peripheral blood picture, reinforcement of internal immunity and inhibition of tumor proliferation. Study and utilization of Agaricus Blazei should be continued as one supplemental method of therapy for acute leukemia because it increases the desirable effect of chemotherapy through reducing the side effects and reinforcing the durability of the body. Our experiment this time has presented an important cause of study and clinical application of Agaricus Blazei and has contributed to its development and utilization.

(Dr. Wang Jun Zhi is a co-researcher of Lanzhou Medicine College, currently at Mie University, Japan.)

Bibliography:

1.T. Mizuno et al. “Studies on the Host-Mediated Antitumor Polysaccharides: Part IX. Fractionation and Characterization of Antitumor Polysaccharides from Maitake, Grifoia Frondosa.” Agric Bio Chem 1986.56.1679

2.Zhang Xiu Wen et al. “Agaricus Blazei’s Influence to Myelopoiesis Cells of Normal Rats” Lanzhou Medical College Academic Report 1993.19(3).143

3.Wang Zhi Jian “Corrective Proposal on the Classification of Acute Nonlymphocytic Leukemia at Leukemia Classification Conference” China Hematology Magazine 1987.3.181

4.Wang Jing et al. “Observation on Treatment Effect of Agaricus Blazei against Alimentary Tract Tumor” Gansu Medical Journal 199