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    Clinical Practice Guideline of Sui Du Lao (Myelodysplastic Syndrome)Committee of Professional and Technical Standards of Hematology of World Federation of Chinese Medicine Societies

    2019-10-12 05:32:40

    ABSTRACT This paper developed a guideline for clinical practice of Sui Du Lao (myelodysplastic syndrome). It covers the traditional Chinese medicine (TCM) disease names, syndrome differentiation, prognostic scores, treatment according to the syndrome differentiation, and efficacy evaluation, and the relationships between dose, efficacy, mechanism, and toxicity of Realgar and emergency plans in patients treated orally with TCM preparation containing Realgar.

    KEYWORDS: Sui Du Lao; Myelodysplastic syndrome; Standards; Guideline; Realgar; Traditional Chinese medicine

    Due to the differences between theoretical systems of traditional Chinese medicine (TCM) and western medicine, the names of hematologic diseases in western medicine and blood diseases in TCM were often confused with each other. Therefore, the standardization of names of hematopoietic system diseases as TCM is helpful not only for clinicians and researchers in clinical application, but also for international academic exchange.

    Myelodysplastic syndrome is one of the dominant diseases of TCM in the treatment of blood diseases. Although the clinical pathways and TCM therapy of myelodysplastic syndrome have been widely accepted and applied in China, it has not yet been used worldwide.

    STANDARD TCM NAME OF MYELODYSPLASTIC SYNDROME

    There was still no TCM name for myelodysplastic syndrome, while the name "myelodysplastic syndrome" in western medicine could not reflect the nature of the disease. A suggestion was made by the Hematology Committee of Chinese Association of Integrative Medicine and the Hematology Group of Internal Medicine Branch of China Association of Chinese Medicine in 2008[1]: Myelodysplastic syndrome can be named as "Sui Du Lao" in TCM. "Sui" indicates the location of the disease; "Du" indicates the nature of the disease; "Lao" indicates the condition of the disease.

    STANDARD OF TCM SYNDROME DIFFERENTIATION OF SUI DU LAO (MYELODYSPLASTIC SYNDROMES)

    Previously, Sui Du Lao (myelodysplastic syndromes) was differentiated and treated with reference to the clinical pathways of second batch of 24 professions 105 diseases published by the National Administration of Traditional Chinese Medicine in 2011. It includes a clinical pathway of Sui Du Lao (myelodysplastic syndromes) (P337)[2], a TCM treatment programs of Sui Du Lao (myelodysplastic syndromes) (P361)[3], and clinical application of TCM diagnosis and treatment scheme for Sui Du Lao (myelodysplastic syndromes)[4].

    Syndrome of deficiency of qi and yin with blockage of toxin and stasis

    The patients are manifested with dim complexion, shortness of breath, spontaneous or night sweating, vexing heat in the five centers (chest, palms and soles), or even nasal bleeding or bloody stool, or skin purpura, and pale tongue with less coating, and deficient and weak pulse.

    Syndrome of deficiency of spleen and kidney with blockage of toxin and stasis

    The patients are manifested with pale complexion, poor appetite and digestion, loose stool, soreness and softness of the waist and knees, fear of cold, or even nasal bleeding or bloody stool, or skin purpura, and pale and enlarged tongue with glossy coating, and deep and thready pulse.

    Syndrome of intense heat-toxin with blockage of toxin and stasis

    The patients are manifested with fever, profuse sweating, and usually nasal bleeding or bloody stool, or skin purpura, dry mouth with bitter taste, strong desire to drink, dry stool, yellow and red urine, red tongue with yellow coating, and surging and rapid pulse.

    STANDARD OF TCM PROGNOSIS SCORE OF SUI DU LAO (MYELODYSPLASTIC SYNDROME)

    According to the common TCM symptoms of Sui Du Lao (myelodysplastic syndromes) and the weight of TCM syndromes on prognosis[5], the TCM prognosis scoring system of Sui Du Lao (myelodysplastic syndromes) was formed (Table 1).

    STANDARDS OF TREATMENT WITH CHINESE MATERIA MEDICA BASED ON TCM SYNDROME DIFFERENTIATION OF SUI DU LAO (MYELODYSPLASTIC SYNDROME)

    Deficiency of qi and yin with blockage of toxin and stasis

    Therapeutic principle

    Benefiting qi and nourishing yin, removing toxins and dissolving blood stasis.

    Recommended prescriptions

    Modified Shengmai Decoction and Dabuyuan Decoction for benefiting qi and nourishing yin. Medicinals including Radix Pseudostellariae, Radix Ophiopogonis, Fructus Schisandrae Chinensis, Radix Rehmanniae Recens, Fructus Corni, Fructus Ligustri Lucidi, Fructus Lycii, Radix Paeoniae Alba, and Radix Asparagi are recommended. Realgar-containing formula such as Qinghuang Powder[9-12], Compound Qinghuang Powder[13-15], Liushen Pills[16], Compound Huangdai Pills[17], Dingqing Pills[18]can be selected for removing toxins and dissolving blood stasis. Or choose the intravenous infusion of arsenic[19,20].

    Deficiency of spleen and kidney with blockage of toxin and stasis

    Therapeutic principle

    Fortifying the spleen and kidney, removing toxins and dissolving blood stasis.

    Recommended prescriptions

    Modified Xiangsha Liujunzi Decoction and Liuwei Dihuang Decoction for fortifying the spleen and kidney. Medicinals including Radix Aucklandiae, Fructus Amomi Villosi, Radix Pseudostellariae, Rhizoma Atractylodis Macrocephalae, Radix Glycyrrhizae, Poria, Radix Rehmanniae Preparata, Fructus Corni, Rhizoma Dioscoreae, Rhizoma Alismatis, and Cortex Moutan Radicis are recommended. Realgar-containing oral formula such as Qinghuang Powder[9-12], Compound Qinghuang Powder[13-15], Liushen Pills[16], Compound Huangdai Pills[17], Dingqing Pills[18]can be selected for removing toxins and dissolving blood stasis. The intravenous infusion of arsenic can be also selected[19,20].

    Table 1. TCM prognosis score of Sui Du Lao (myelodysplastic syndromes)

    Intense heat-toxin with blockage of toxin and stasis

    Therapeutic principle

    Clearing heat and dispelling pathogen, resovling toxins and dissolving blood stasis.

    Recommended prescriptions

    Modified Baihu Decoction and Xijiao Dihuang Decoction for clearing heat and dispelling pathogen. Medicinals including Gypsum Fibrosum, Rhizoma Anemarrhenae, Radix Glycyrrhizae, Cornu Bubali, Radix Rehmanniae Recens, Cortex Moutan Radicis, and Radix Scrophulariae are recommended. Realgar-containing formula such as Qinghuang Powder[9-12], Compound Qinghuang Powder[13-15], Liushen Pills[16], Compound Huangdai Pills[17], Dingqing Pills[18]can be selected for removing toxins and dissolving blood stasis. Or choose the intravenous infusion of arsenic[19,20].

    STANDARD OF CURATIVE EFFECT EVALUATION OF SUI DU LAO (MYELODYSPLASTIC SYNDROME) BASED ON TCM SYNDROMES

    Scores of TCM syndromes

    Using the TCM prognosis scores (Table 1) of Sui Du Lao (myelodysplastic syndromes).

    Evaluation of curative effect on TCM syndromes

    Using the Nimodipine method.

    Calculation formula: [(Pre-treatment syndrome scores - post-treatment syndrome scores) / pre-treatment syndrome scores] × 100%.

    Standard of curative effect evaluation based on TCM syndromes

    Clinical cure: TCM clinical symptoms and signs completely disappear, with the syndrome scores decreased

    Markedly effective: TCM clinical symptoms and signs were significantly improved, with the syndrome scores decreased

    Effective: TCM clinical symptoms and signs were partly improved, with the syndrome scores decreased

    Invalid: TCM clinical symptoms and signs were not significantly improved or even become worse, with the syndrome scores decreased < 30%.

    STANDARD OF REALGAR-CONTAINING ORAL CHINESE MEDICINE PREPARATION FOR TREATMENT OF SUI DU LAO (MYELODYSPLASTIC SYNDROME)

    Realgar-containing oral Chinese medicine

    Qinghuang Powder[9-12], Compound Qinghuang Powder[13-15], Liushen Pills[16], Compound Huangdai Pills[17], Dingqing Pills[18], etc.

    Quality standards of Realgar

    Realgar was grounded with water and then dried into powder. As the effective component, arsenic disulfide (As2S2) should be no less than 90.0%[21].

    Main mechanism of Realgar

    To induce apoptosis of malignant cells, promote differentiation of diseased cells into normal cells, and regulate abnormal methylation[22-25].

    Initial dose of Realgar for oral administration

    0.1 g/day, according to Pharmacopoeia of People's Republic of China (1995-2015 edition)[21].

    Effective serum arsenic concentration of orally administrated Realgar

    The initial effective concentration of arsenic is 20 μg/L, with no further effect observed when blood concentration of arsenic > 50 μg/L[13,14].

    Dosage adjustment of Realgar for oral administration

    The dose of realgar can be increased by 0.1 g/d each in patients whose arsenic concentrations were less than 20 μg/L. The maximum dose of Realgar is 0.3 g/d[13,14].

    Restrictions on the application of Realgar for oral administration

    The dose of realgar would be halved when the peak blood concentration of arsenic is more than 140 μg/L, and treatment would be discontinued when the peak blood concentration of arsenic reached 940 μg/L[26].

    SAFETY STANDARD OF REALGARCONTAINING ORAL CHINESE MEDICINE PREPARATION FOR TREATMENT OF SUI DU LAO (MYELODYSPLASTIC SYNDROME) [14, 27-31]

    Age range

    Between 18 and 75 years old.

    Clinical adverse reactions

    Nausea, anorexia, abdominal pain, diarrhea, numbness of the limbs, itchy skin, keratinized skin, facial edema, etc.

    Organ function to be monitored

    Cardiac function, liver function, and kidney function.

    Classification of clinical adverse reaction

    Referring to the Guiding Principle of Clinical Research on New Traditional Chinese Drugs (2002 edition): (1) Mild adverse reaction: the participants can tolerate the side effect of the treatment and continue with the study without other disposition. And it has not obvious damage on the participants' health. (2) Moderate adverse reaction: the participants' health was damaged and they cannot tolerate the side effect. And the therapy has curtain impact on the participants' health. (3) Severe adverse reaction: the side effects jeopardize the life of the subjects who are threatened by disability or mortality risk. They need to stop the treatment and be disposed immediately.

    EMERGENCY PLANS FOR SIDE EFFECTS CAUSED BY ORAL ADMINISTRATION OF REALGAR-CONTAINING CHINESE MEDICINE PREPARATION FOR TREATMENT OF SUI DU LAO (MYELODYSPLASTIC SYNDROME)[32-34]

    Chinese material medica

    Radix Glycyrrhizae 30 g, mung bean 30 g, or using Radix Stephaniae Tetrandrae 30 g, and take decoctions frequently.

    Western medicine

    Intramuscular injection of sodium dimercaptopropyl sulfonate, 5 mg/kg each time, 3-4 times on the first day, 2-3 times on the next day, and 1-2 times/d from the third day, for 7 days.

    Writers:Liu Weiyi, Chen Zhuo

    Final review expert:Hu Xiaomei

    The experts participating in the development of the guideline:

    Hu Xiaomei (Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing Institute of Integrated Traditional and Western Medicine, China), Zhou Yongming (Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China), Lu Jiahui (Shanghai Chinese Medicine Hospital, China), Shi Zhexin (First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, China), Sun Xuemei (Jiangsu Provincial Hospital of Traditional Chinese Medicine, China), Yang Tonghua (Yunnan Province Hospital of Blood Disease, China), Xu Ruirong (First Affiliated Hospital of Shandong University of Traditional Chinese Medicine, China), Chen Bin (Hubei Provincial Hospital of Traditional Chinese Medicine, China), Hirano Toshihiko (Tokyo University of Pharmacy and Life Sciences, Japan,), Wang Zhanxiang (National University of Health Sciences, US), Wu Xiaosheng (Mayo Clinic, US).

    ACKNOWLEDGEMENT

    This study was financially supported by Beijing Municipal Science & Technology Commission (No. Z141100006014003), National Natural Science Foundation of China (No. 81673821), Special Research Foundation of Central Level Public Scientific Research Institutes (ZZ10-016).

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