More Benefits of Oral Administration of Arsenic-containing Qinghuang Powder Compared with Decitabine for High/Very-high Risk Myelodysplastic Syndrome
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摘要
OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to the Revised International Prognostic Score System. METHODS: The OS(mOS) rate, annual OS rate and progression to acute myeloid leukemia(AML) in patients with H/VH MDS treated with QHP(QHP group, n = 27) and decitabine(decitabine group, n = 20) were retrospectively analyzed. The effects of prognostic factors of age, proportion of bone marrow blast,peripheral blood cell count, karyotype and Charlson Comorbidity Index(CCI) on OS were further analyzed. RESULTS: The m OS rate of QHP group(29 months) was signi?cantly longer than that of the decitabine group(18 months)(P = 0.043). The OS rates of 1, 2, and 3 years were signi?cantly higher in the QHP group(88.9%, 59.3%, 29.6%) than that in the decitabine group(70%, 25%, and 5%)(P = 0.01). There was no signi?cant difference of 5-year OS rate between the 2 groups(P = 0.133).The effects of prognostic factors on mOS were further analyzed, and it was found that there was no signi?cant difference of m OS rate between the QHP group(29 months) and the decitabine group(21 months) in the patients with age 65 years old(P = 0.673). The mOS rate was signi?cantly longer in QHP group(28.5 months) than that in decitabine group(18 months) in the patients with age of < 65 years old(P = 0.04). The proportions of bone marrow blast cells with 10% or < 10% had no signi?cant effects on the mOS rate of patients in the 2 groups(P = 0.429, P = 0.183). In patients with HGB 80 g/L, mOS rate was signi?cantly longer in the QHP group(57 months) than that in the decitabine group(21 months)(P = 0.047), while in patients with HGB < 80 g/L, there was no signi?cant difference of mOS rate between the 2 groups(P = 0.265). In the patients with PLT < 50×10~9/L, the mOS rate was signi?cantly longer in the QHP group(33 months) than that in the decitabine group(16 months)(P = 0.028). In the patients with PLT 50×10~9/L, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.338). In the patients with ANC < 0.8×10~9/L, the mOS rate was signi?cantly longer in the QHP group(20 months) than that in the decitabine group(7 months)(P = 0.014). In the patients with normal karyotype, the mOS was signi?cantly longer in the QHP group(32 months) than that in the decitabine group(15 months)(P = 0.009). In the patients with abnormal karyotypes, there was no significant difference of the mOS rate between the 2 groups(P = 0.882). In the patients with good karyotypes, the mOS rate was signi?cantly longer in the QHP group(37 months) than that in the decitabine group(20 months)(P = 0.019). In the patients with moderate/poor/very poor karyotype, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.685). In the patients with CCI 3, the mOS rate was signi?cantly longer in the QHP group(34 months) than that in the decitabine group(10.5 months)(P = 0.017). In patients with CCI < 3, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.581). The proportion of progression to AML in the QHP group(18.8%) was signi?cantly lower than that in the decitabine group(25%)(P = 0.03). CONCLUSION: Compared with decitabine, oral administration of arsenic-containing Qinghuang Powder could help patients to survive longer and decrease incidence of progression to acute myeloid leukemia in the treatment of patients with high/very high MDS.
OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to the Revised International Prognostic Score System. METHODS: The OS(mOS) rate, annual OS rate and progression to acute myeloid leukemia(AML) in patients with H/VH MDS treated with QHP(QHP group, n = 27) and decitabine(decitabine group, n = 20) were retrospectively analyzed. The effects of prognostic factors of age, proportion of bone marrow blast,peripheral blood cell count, karyotype and Charlson Comorbidity Index(CCI) on OS were further analyzed. RESULTS: The m OS rate of QHP group(29 months) was signi?cantly longer than that of the decitabine group(18 months)(P = 0.043). The OS rates of 1, 2, and 3 years were signi?cantly higher in the QHP group(88.9%, 59.3%, 29.6%) than that in the decitabine group(70%, 25%, and 5%)(P = 0.01). There was no signi?cant difference of 5-year OS rate between the 2 groups(P = 0.133).The effects of prognostic factors on mOS were further analyzed, and it was found that there was no signi?cant difference of m OS rate between the QHP group(29 months) and the decitabine group(21 months) in the patients with age 65 years old(P = 0.673). The mOS rate was signi?cantly longer in QHP group(28.5 months) than that in decitabine group(18 months) in the patients with age of < 65 years old(P = 0.04). The proportions of bone marrow blast cells with 10% or < 10% had no signi?cant effects on the mOS rate of patients in the 2 groups(P = 0.429, P = 0.183). In patients with HGB 80 g/L, mOS rate was signi?cantly longer in the QHP group(57 months) than that in the decitabine group(21 months)(P = 0.047), while in patients with HGB < 80 g/L, there was no signi?cant difference of mOS rate between the 2 groups(P = 0.265). In the patients with PLT < 50×10~9/L, the mOS rate was signi?cantly longer in the QHP group(33 months) than that in the decitabine group(16 months)(P = 0.028). In the patients with PLT 50×10~9/L, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.338). In the patients with ANC < 0.8×10~9/L, the mOS rate was signi?cantly longer in the QHP group(20 months) than that in the decitabine group(7 months)(P = 0.014). In the patients with normal karyotype, the mOS was signi?cantly longer in the QHP group(32 months) than that in the decitabine group(15 months)(P = 0.009). In the patients with abnormal karyotypes, there was no significant difference of the mOS rate between the 2 groups(P = 0.882). In the patients with good karyotypes, the mOS rate was signi?cantly longer in the QHP group(37 months) than that in the decitabine group(20 months)(P = 0.019). In the patients with moderate/poor/very poor karyotype, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.685). In the patients with CCI 3, the mOS rate was signi?cantly longer in the QHP group(34 months) than that in the decitabine group(10.5 months)(P = 0.017). In patients with CCI < 3, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.581). The proportion of progression to AML in the QHP group(18.8%) was signi?cantly lower than that in the decitabine group(25%)(P = 0.03). CONCLUSION: Compared with decitabine, oral administration of arsenic-containing Qinghuang Powder could help patients to survive longer and decrease incidence of progression to acute myeloid leukemia in the treatment of patients with high/very high MDS.
OBJECTIVE: To evaluated the benefits of oral administration of arsenic-containing Qinghuang Powder(QHP)compared with decitabine for patients with high/very-high(H/VH) risk myelodysplastic syndrome(MDS) according to the Revised International Prognostic Score System. METHODS: The OS(mOS) rate, annual OS rate and progression to acute myeloid leukemia(AML) in patients with H/VH MDS treated with QHP(QHP group, n = 27) and decitabine(decitabine group, n = 20) were retrospectively analyzed. The effects of prognostic factors of age, proportion of bone marrow blast,peripheral blood cell count, karyotype and Charlson Comorbidity Index(CCI) on OS were further analyzed. RESULTS: The m OS rate of QHP group(29 months) was signi?cantly longer than that of the decitabine group(18 months)(P = 0.043). The OS rates of 1, 2, and 3 years were signi?cantly higher in the QHP group(88.9%, 59.3%, 29.6%) than that in the decitabine group(70%, 25%, and 5%)(P = 0.01). There was no signi?cant difference of 5-year OS rate between the 2 groups(P = 0.133).The effects of prognostic factors on mOS were further analyzed, and it was found that there was no signi?cant difference of m OS rate between the QHP group(29 months) and the decitabine group(21 months) in the patients with age 65 years old(P = 0.673). The mOS rate was signi?cantly longer in QHP group(28.5 months) than that in decitabine group(18 months) in the patients with age of < 65 years old(P = 0.04). The proportions of bone marrow blast cells with 10% or < 10% had no signi?cant effects on the mOS rate of patients in the 2 groups(P = 0.429, P = 0.183). In patients with HGB 80 g/L, mOS rate was signi?cantly longer in the QHP group(57 months) than that in the decitabine group(21 months)(P = 0.047), while in patients with HGB < 80 g/L, there was no signi?cant difference of mOS rate between the 2 groups(P = 0.265). In the patients with PLT < 50×10~9/L, the mOS rate was signi?cantly longer in the QHP group(33 months) than that in the decitabine group(16 months)(P = 0.028). In the patients with PLT 50×10~9/L, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.338). In the patients with ANC < 0.8×10~9/L, the mOS rate was signi?cantly longer in the QHP group(20 months) than that in the decitabine group(7 months)(P = 0.014). In the patients with normal karyotype, the mOS was signi?cantly longer in the QHP group(32 months) than that in the decitabine group(15 months)(P = 0.009). In the patients with abnormal karyotypes, there was no significant difference of the mOS rate between the 2 groups(P = 0.882). In the patients with good karyotypes, the mOS rate was signi?cantly longer in the QHP group(37 months) than that in the decitabine group(20 months)(P = 0.019). In the patients with moderate/poor/very poor karyotype, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.685). In the patients with CCI 3, the mOS rate was signi?cantly longer in the QHP group(34 months) than that in the decitabine group(10.5 months)(P = 0.017). In patients with CCI < 3, there was no signi?cant difference of the mOS rate between the 2 groups(P = 0.581). The proportion of progression to AML in the QHP group(18.8%) was signi?cantly lower than that in the decitabine group(25%)(P = 0.03). CONCLUSION: Compared with decitabine, oral administration of arsenic-containing Qinghuang Powder could help patients to survive longer and decrease incidence of progression to acute myeloid leukemia in the treatment of patients with high/very high MDS.
引文
1. NCCN Clinical Practice Guidelines in Oncology(NCCN Guidelines):Myelodysplastic Syndromes(Version 1, 2018).http://www.nccn.org.[2017-08-29]
2. Steensma DP. Can hypomethylating agents provide a platform for curative therapy in myelodysplastic syndromes?Best Practice and Research Clinical Haematology,2012,25:443-451.
3. Laribi K,Bolle D,Alani M,Prognostic impact of elevated pretreatment serum ferritin in patients with high-risk MDS treated with azacitidine. Experimental Hematology, 2018,65:34-37.
4. Sohn SK, Moon JH, Lee IH, et al. No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome. The Korean Journal of Internal Medicine, 2017, 33(6):1194-1202.
5. Xu S, Hu XM, Xu YG, etc. Clinical observation on treatment of myelodysplastic syndrome with Qinghuang Powder and kidney-tonifying and spleen-invigorating traditional Chinese Medicine. Chinese Journal of Integrated Traditional Chinese and Western Medicine, 2008, 28(3):216-219.
6. Xu S,Ma R,Hu XM, et al. Clinical observation of the treatment of myelodysplastic syndrome Mainly with Qinghuang Powder. Chinese Journal of Integrative Medicine,2011,17(11):834-839.
7. Zhou QB, Wang HZ, Yang XH, etc. Clinical observation on308 cases of myelodysplastic syndrome complicated with multilineal dysplasia treated with Qinghuang Powder as the main scheme. Journal of Leukemia and Lymphoma, 2015,01:54-57.
8. Zhu QZ, Hu XM, Wang HZ, etc. A retrospective analysis of150 cases of myelodysplastic syndrome treated mainly with Qinghuang Powder capsule was made. Journal of Traditional Chinese Medicine, 2018, 59(4):303-306.
9. Gao F, Ma R, Hu XM, et al. Long-term efficacy of Qinghuang Powder in the treatment of myelodysplastic syndrome(MDSRAEB)with primordial cell elevation. Journal of Clinical Hematology,2013, 26(1):16-18.
10. Wang Y, Fang S, Deng ZY, et al. Curative effect analysis of compound Qinghuang Powder on myelodysplastic syndrome.International Journal of Traditional Chinese Medicine, 2015,37(12):1091-1095.
11. Ma JL, Qu WW, Hu XM. Study on the correlation between clonal selectivity of and the effect of arsenic in vivo in the treatment of myelodysplastic syndrome with Qinghuang Powder, a traditional Chinese medicine compound. Chinese Journal of Traditional Chinese Medicine Information, 2013,20(6):5-8.
12. Sun SZ, Ma R, Hu XM, et al. Karyotype and DNA-mthylation responses in myelodysplastic syndromes following treatment with traditional Chinese formula containing arsenic. Evidencebased Complementary and Alternative Medicine, 2012,2012:969476.
13. Hu XM,Tanaka S,Onda K,et al. Arsenic disulfide induced apoptosis and concurrently promoted erythroid differentiation in cytokine-dependent MDS-progressed leukemia cell line F-36p with complex karyotype including monosomy 7. Chinese Journal of Integrative Medicine,2014,20(5):387-393.
14. Hu XM,Yuan B,Tanaka S,et al. Arsenic disulfide-triggered apoptosis and erythroid differentiation in myelodysplastic syndrome and acute myeloid leukemia cell lines. Hematology,2014, 19(6):352-360
15. Wang Y,Song MM,Fang S,et al. Clinical safety analysis of compound qinghuang powder in treatment of myelodysplastic syndrome. International Journal of Traditional Chinese Medicine, 2014, 36(12):1074-1077.
16. Deng ZY, Fang S, Wang HZ, et al. Clinical efficacy and safety of compound Qinghuang Powder in the treatment of myelodysplastic syndrome and its correlation with serum arsenic concentration. Journal of Leukemia and Lymphoma,2017, 26(5):261-266.
17. Zhu QZ,Deng ZY,Wang MJ,et al. Analysis of blood arsenic concentration and clinical safety in patients with myelodysplastic syndrome treated with traditional Chinese medicine compound Qinghuang Powder containing arsenic.International Journal of Traditional Chinese Medicine, 2017,39(11):976-980.
18. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system(IPSS-R)for myelodysplastic syndrome. Blood, 2012, 120:2454-2465.
19. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabineimproves patient outcomes in myelodysplastic syndromes:results of a phaseⅢrandomized study. Cancer, 2006,106(8):1794-1803.
20. Lubbert M, Suciu S, Baila L, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate-or high-risk myelodysplastic syndrome(MDS)ineligible for intensive chemotherapy:final results of the randomized phaseⅢstudy of the European Organization for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. 2011, 29(15):1987-1996.
21. Schuler E, Zadrozny N, Blum S, et al. Long-term outcome of high risk patients with myelodysplastic syndromes or secondary acute myeloid leukemia receiving intensive chemotherapy.Annals of Hematology, 2018, 97(12):2325-2332.
22. Mozessohn L,Cheung MC, Fallahpour S,et al. Azacitidinc in the"real-world":an evaluation of 1101 higher-risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada. British Journal of Haematology. 2018, 181(6):803-815.
23. Garcia-Manero G, Montalban-Bravo G, Berdeja JG, et al.Phase 2, randomized, double-blind study of pracinostat in combination with azacitidine in patients with untreated,higher-risk myelodysplastic syndromes. Cancer, 2017,123(6):994-1002.
24. Kawabata H,Tohyama K,Matsuda A,et al. Validation of the revised International Prognostic Scoring System in patients with myelodysplastic syndrome in Japan:results from a prospective multicenter registry. International Journal of Hematology,2017, 106(3):375-384.
25. Merkel D, Filanovsky K, Gafter-Gvili A, et al. Predicting infections in high-risk patients with myelodysplastic syndrome/acute myeloid leukemia treated with azacitidine:a retrospective multicenter study. American Journal Hematology, 2013, 88(2):130-134.
26. Hu XM,Ma R, Xu YG,et al. Application of Qinghuang Powder in the treatment of malignant hematological diseases.International Journal of Traditional Chinese Medicine, 2011,33(6):568-570.
27. Sperr WR, Wimazal F, Kundi M, et al. Comorbidity as prognostic variable in MDS:comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS Study Group. Annals of Oncology, 2010,21(1):114-119.
2. Steensma DP. Can hypomethylating agents provide a platform for curative therapy in myelodysplastic syndromes?Best Practice and Research Clinical Haematology,2012,25:443-451.
3. Laribi K,Bolle D,Alani M,Prognostic impact of elevated pretreatment serum ferritin in patients with high-risk MDS treated with azacitidine. Experimental Hematology, 2018,65:34-37.
4. Sohn SK, Moon JH, Lee IH, et al. No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome. The Korean Journal of Internal Medicine, 2017, 33(6):1194-1202.
5. Xu S, Hu XM, Xu YG, etc. Clinical observation on treatment of myelodysplastic syndrome with Qinghuang Powder and kidney-tonifying and spleen-invigorating traditional Chinese Medicine. Chinese Journal of Integrated Traditional Chinese and Western Medicine, 2008, 28(3):216-219.
6. Xu S,Ma R,Hu XM, et al. Clinical observation of the treatment of myelodysplastic syndrome Mainly with Qinghuang Powder. Chinese Journal of Integrative Medicine,2011,17(11):834-839.
7. Zhou QB, Wang HZ, Yang XH, etc. Clinical observation on308 cases of myelodysplastic syndrome complicated with multilineal dysplasia treated with Qinghuang Powder as the main scheme. Journal of Leukemia and Lymphoma, 2015,01:54-57.
8. Zhu QZ, Hu XM, Wang HZ, etc. A retrospective analysis of150 cases of myelodysplastic syndrome treated mainly with Qinghuang Powder capsule was made. Journal of Traditional Chinese Medicine, 2018, 59(4):303-306.
9. Gao F, Ma R, Hu XM, et al. Long-term efficacy of Qinghuang Powder in the treatment of myelodysplastic syndrome(MDSRAEB)with primordial cell elevation. Journal of Clinical Hematology,2013, 26(1):16-18.
10. Wang Y, Fang S, Deng ZY, et al. Curative effect analysis of compound Qinghuang Powder on myelodysplastic syndrome.International Journal of Traditional Chinese Medicine, 2015,37(12):1091-1095.
11. Ma JL, Qu WW, Hu XM. Study on the correlation between clonal selectivity of and the effect of arsenic in vivo in the treatment of myelodysplastic syndrome with Qinghuang Powder, a traditional Chinese medicine compound. Chinese Journal of Traditional Chinese Medicine Information, 2013,20(6):5-8.
12. Sun SZ, Ma R, Hu XM, et al. Karyotype and DNA-mthylation responses in myelodysplastic syndromes following treatment with traditional Chinese formula containing arsenic. Evidencebased Complementary and Alternative Medicine, 2012,2012:969476.
13. Hu XM,Tanaka S,Onda K,et al. Arsenic disulfide induced apoptosis and concurrently promoted erythroid differentiation in cytokine-dependent MDS-progressed leukemia cell line F-36p with complex karyotype including monosomy 7. Chinese Journal of Integrative Medicine,2014,20(5):387-393.
14. Hu XM,Yuan B,Tanaka S,et al. Arsenic disulfide-triggered apoptosis and erythroid differentiation in myelodysplastic syndrome and acute myeloid leukemia cell lines. Hematology,2014, 19(6):352-360
15. Wang Y,Song MM,Fang S,et al. Clinical safety analysis of compound qinghuang powder in treatment of myelodysplastic syndrome. International Journal of Traditional Chinese Medicine, 2014, 36(12):1074-1077.
16. Deng ZY, Fang S, Wang HZ, et al. Clinical efficacy and safety of compound Qinghuang Powder in the treatment of myelodysplastic syndrome and its correlation with serum arsenic concentration. Journal of Leukemia and Lymphoma,2017, 26(5):261-266.
17. Zhu QZ,Deng ZY,Wang MJ,et al. Analysis of blood arsenic concentration and clinical safety in patients with myelodysplastic syndrome treated with traditional Chinese medicine compound Qinghuang Powder containing arsenic.International Journal of Traditional Chinese Medicine, 2017,39(11):976-980.
18. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system(IPSS-R)for myelodysplastic syndrome. Blood, 2012, 120:2454-2465.
19. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabineimproves patient outcomes in myelodysplastic syndromes:results of a phaseⅢrandomized study. Cancer, 2006,106(8):1794-1803.
20. Lubbert M, Suciu S, Baila L, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate-or high-risk myelodysplastic syndrome(MDS)ineligible for intensive chemotherapy:final results of the randomized phaseⅢstudy of the European Organization for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. 2011, 29(15):1987-1996.
21. Schuler E, Zadrozny N, Blum S, et al. Long-term outcome of high risk patients with myelodysplastic syndromes or secondary acute myeloid leukemia receiving intensive chemotherapy.Annals of Hematology, 2018, 97(12):2325-2332.
22. Mozessohn L,Cheung MC, Fallahpour S,et al. Azacitidinc in the"real-world":an evaluation of 1101 higher-risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada. British Journal of Haematology. 2018, 181(6):803-815.
23. Garcia-Manero G, Montalban-Bravo G, Berdeja JG, et al.Phase 2, randomized, double-blind study of pracinostat in combination with azacitidine in patients with untreated,higher-risk myelodysplastic syndromes. Cancer, 2017,123(6):994-1002.
24. Kawabata H,Tohyama K,Matsuda A,et al. Validation of the revised International Prognostic Scoring System in patients with myelodysplastic syndrome in Japan:results from a prospective multicenter registry. International Journal of Hematology,2017, 106(3):375-384.
25. Merkel D, Filanovsky K, Gafter-Gvili A, et al. Predicting infections in high-risk patients with myelodysplastic syndrome/acute myeloid leukemia treated with azacitidine:a retrospective multicenter study. American Journal Hematology, 2013, 88(2):130-134.
26. Hu XM,Ma R, Xu YG,et al. Application of Qinghuang Powder in the treatment of malignant hematological diseases.International Journal of Traditional Chinese Medicine, 2011,33(6):568-570.
27. Sperr WR, Wimazal F, Kundi M, et al. Comorbidity as prognostic variable in MDS:comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS Study Group. Annals of Oncology, 2010,21(1):114-119.
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