The consensus on the diagnosis and treatment of elderly myelodysplastic neoplasm in China (2024)

  • MDS Professional Committee of Hematology Branch of Chinese Geriatrics Society
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Received date: 2024-04-16

  Accepted date: 2024-05-20

  Online published: 2024-06-25

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid tumours originating from haematopoietic stem/progenitor cells, with a high prevalence in the elderly. Epidemiological surveys in Europe and the United States have revealed that the incidence of MDS is (4-5)/100 000, which increases with age,and the median age at diagnosis of MDS patients reaches 73-76 years. In Shanghai, China, according to the World Health Organization (WHO) 2008 diagnostic criteria, the average incidence rate was 1.51/100 000, and the median age of onset of MDS was found to be 62 years old in a survey conducted in 3.9 million people from 2004 to 2007, of which about one-third of the patients would be transformed into acute myeloid leukemia (AML), and 53% of the patients would die due to infections, haemorrhages, or comorbidities triggered by cytopenias. Elderly MDS patients have their own characteristics in terms of both treatment choices and disease prognosis due to more comorbidities and weaker health. Clinical characteristics of elderly MDS patients include slightly higher white blood cell count, haemoglobin level and more bone marrow blasts than those of young patients, while neutrophil count and platelet count are significantly higher than those of young patients; the number of mutations in elderly MDS patients is higher, with an average of 1.8 mutations per patient, among which the mutations in ASXL1, TET2, SF3B1, STAG2, SRSF2 and TP53 are more common; while the number of mutations in younger patients averages 1.2 per person, among which U2AF1, ASXL1 and RUNX1 mutations are more common. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for MDS, and myeloablative transplantation is feasible in young patients, but only reduced-intensity conditioning (RIC) allo-HSCT can be performed in elderly patients.The natural course and prognosis of elderly MDS patients varies considerably, and the MDS Composite Prognostic Score, which is composed of the composite age (>70 years old), vulnerability index, and IPSS prognostic subgroups, is able to better predict the tolerance of chemotherapy and adverse treatment effects in MDS patients. This consensus is based on the latest evidence-based data in the study of MDS in the elderly at home and abroad, and has been discussed by the experts of the group, which aims to standardise the diagnosis and the whole management of treatment for elderly MDS patients in China.

Cite this article

MDS Professional Committee of Hematology Branch of Chinese Geriatrics Society . The consensus on the diagnosis and treatment of elderly myelodysplastic neoplasm in China (2024)[J]. Journal of Diagnostics Concepts & Practice, 2024 , 23(03) : 285 -296 . DOI: 10.16150/j.1671-2870.2024.03.006

References

[1] WANG W, WANG H, WANG X Q, et al. First report of incidence of adult myelodysplastic syndrome in China[J]. Ann Hematol, 2012, 91(8):1321-1322.
[2] 中华人民共和国老年人权益保障法[EB/OL]. https://www.gov.cn/guoqing/2021-10/29/content_5647622.htm
[3] ADRIANZEN-HERRERA D, SPARKS A D, SINGH R, et al. Impact of preexisting autoimmune disease on myelodysplastic syndromes outcomes: a population analysis[J]. Blood Adv, 2023, 7(22):6913-6922.
[4] 钱军, 常春康. 骨髓增生异常综合征鉴别诊断与治疗[M]. 北京: 科学技术文献出版社, 2020.
  QIAN J, CHANG C K. Differential diagnosis and treatment of myelodysplastic syndrome[M]. Beijing: Scientific and Technical Documenttion Press, 2020.
[5] BECK D B, FERRADA M A, SIKORA K A, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease[J]. N Engl J Med, 2020, 383(27):2628-2638.
[6] KHOURY J D, SOLARY E, ABLA O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms[J]. Leukemia, 2022, 36(7):1703-1719.
[7] LEE W H, LIN C C, WANG Y H, et al. Distinct genetic landscapes and their clinical implications in younger and older patients with myelodysplastic syndromes[J]. Hematol Oncol, 2023, 41(3):463-473.
[8] PORWIT A, BéNé M C, DUETZ C, et al. Multipara-meter flow cytometry in the evaluation of myelodysplasia: Analytical issues: Recommendations from the European Leukemia Net/International Myelodysplastic Syndrome Flow Cytometry Working Group[J]. Cytometry B Clin Cytom, 2023, 104(1):27-50.
[9] ARBER D A, ORAZI A, HASSERJIAN R P, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data[J]. Blood, 2022, 140(11):1200-1228.
[10] AKKARI Y M N, BAUGHN L B, DUBUC A M, et al. Guiding the global evolution of cytogenetic testing for hematologic malignancies[J]. Blood, 2022, 139(15):2273-2284.
[11] 中华医学会血液学分会. 骨髓增生异常综合征中国诊断与治疗指南(2019年版)[J]. 中华血液学杂志, 2019, 40(2):89-97.
  Chinese Society of Hematology. Chinese Medical Association[J]. Zhonghua Xue Ye Xue Za Zhi, 2019, 40(2):89-97.
[12] BERNARD E, TUECHLER H, GREENBERG P L, et al. Molecular International Prognostic Scoring System for myelodysplastic syndromes[J]. NEJM Evid, 2022, 1(7):EVIDoa2200008.
[13] VALENT P, ORAZI A, STEENSMA D P, et al. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions[J]. Oncotarget, 2017, 8(43):73483-73500.
[14] MOLGA A, WALL M, CHHETRI R, et al. Comprehensive geriatric assessment predicts azacitidine treatment duration and survival in older patients with myelodysplastic syndromes[J]. J Geriatr Oncol, 2020, 11(1):114-120.
[15] BUCKSTEIN R J. Integrating patient-centered factors in the risk assessment of MDS[J]. Hematology Am Soc Hematol Educ Program, 2019, 2019(1):373-380.
[16] THOMOPOULOS T P, PAPPA V, PAPAGEORGIOU S G. Comorbidities and frailty predict outcome of patients with myelodysplastic syndromes. Should we integrate them in novel prognostic scoring systems?[J] J Geriatr Oncol, 2021, 12(7):1122-1129.
[17] 韩丹丹, 完晓菊, 陈洋, 等. 1例脐血移植植入失败伴免疫性血小板输注无效MDS患者报告[J]. 安徽医学, 2023,44(8):900-902.
  HAN DD, WAN XJ, CHEN Y, et al. MDS patient with failed umbilical cord blood transplantation and ineffective immune platelet transfusion: A case report[J]. Anhui Med, 2023,44(8):900-902.
[18] WONG J, JACKSON R, CHEN L, et al. Determination of age-dependent bone marrow normocellularity[J]. Am J Clin Pathol, 2024, 161(2):170-176.
[19] ARBER D A, ORAZI A, HASSERJIAN R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood, 2016, 27(20):2391-2405.
[20] KUENDGEN A, NOMDEDEU M, TUECHLER H, et al. Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification-an approach to classification of patients with t-MDS[J]. Leukemia, 2021, 35(3):835-849.
[21] PLATZBECKER U, DELLA PORTA M G, SANTINI V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial[J]. Lancet, 2023, 402(10399):373-385.
[22] OLIVA E N, RIVA M, NISCOLA P, et al. Eltrombopag for low-risk myelodysplastic syndromes with thrombocytopenia: interim results of a phase Ⅱ, randomized, placebo-controlled clinical trial (EQOL-MDS)[J]. J Clin Oncol, 2023, 41(28):4486-4496.
[23] ALKHARABSHEH O A, SAADEH S S, ZBLEWSKI D L, et al. Frequency of venous thrombotic events in patients with myelodysplastic syndrome and 5q deletion syndrome during lenalidomide therapy[J]. Ann Hematol, 2019, 98(2):331-337.
[24] 中国老年医学学会周围血管疾病管理分会, 赵纪春, 黄建华, 等. 老年人静脉血栓栓塞症防治中国专家共识[J]. 中国普外基础与临床杂志, 2023, 30(10):1173-1187.
  Peripheral Vascular Disease Management Branch of Chinese Geriatrics Society, ZHAO J C, HUANG J H, et al. Chinese expert consensus on the prevention and treatment of venous thromboembolism in the elderly[J]. Chin J Bases Clin Gen Surg, 2023, 30(10):1173-1187.
[25] STAHL M, DEVEAUX M, DE WITTE T, et al. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort[J]. Blood Adv, 2018, 2(14):1765-1772.
[26] KULASEKARARAJ A, CAVENAGH J, DOKAL I, et al. Guidelines for the diagnosis and management of adult aplastic anaemia: A British Society for Haematology Guideline[J]. Br J Haematol, 2024, 204(3):784-804.
[27] SANTINI V. How I treat MDS after hypomethylating agent failure[J]. Blood, 2019, 133(6):521-529.
[28] LEVITZ D, SAUNTHARARAJAH Y, FEDOROV K, et al. A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML[J]. Clin Cancer Res, 2023, 29(15):2774-2780.
[29] XIAO Z, LIU L, XU Z, et al. Low-dose melphalan in myelodysplastic syndromes: an effective treatment for elderly RAEB-Ⅰ or Ⅱ patients[J] Leuk Lymphoma, 2010, 51(3):549-551.
[30] ORAN B, AHN K W, FRETHAM C, et al. Fludarabine and melphalan compared with reduced doses of busulfan and fludarabine improve transplantation outcomes in older patients with myelodysplastic syndromes[J]. Transplant Cell Ther, 2021, 27(11):921.e1-921.e10.
[31] PLATZBECKER U. Treatment of MDS[J]. Blood, 2019, 133(10):1096-1107.
[32] DEFILIPP Z, CIUREA S O, CUTLER C, et al. Hematopoietic cell transplantation in the management of myelodysplastic syndrome: an evidence-based review from the American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines[J]. Transplant Cell Ther, 2023, 29(2):71-81.
[33] 中国老年医学学会高血压分会, 北京高血压防治协会, 国家老年疾病临床医学研究中心(中国人民解放军总医院,首都医科大学宣武医院). 中国老年高血压管理指南2023[J]. 中华高血压杂志, 2023, 31(6):508-538.
  Hypertension Branch of Chinese Geriatric Society, Beijing Hypertension Prevention and Treatment Association, National Clinical Research Center for Geriatric Diseases (General Hospital of Chinese People's Liberation Army, Xuanwu Hospital, Capital Medical University). General Hospital of Chinese People's Liberation Army, Xuanwu Hospital, Capital Medical University). Guidelines for management of hypertension in China 2023[J]. Chin J Hypertens, 2023, 31(6):508-538.
[34] PAVLIDIS G, PAPAGEORGIOU S G, BAZANI E, et al. Discontinuation of the renin-angiotensin system inhibitors improves erythropoiesis in patients with lower-risk myelodysplastic syndromes[J]. Ther Adv Hematol, 2021, 12:2040620720958299.
[35] ADRIANZEN HERRERA D, PRADHAN K, SNYDER R, et al. Myelodysplastic syndromes and the risk of cardiovascular disease in older adults: A SEER-medicare analysis[J]. Leukemia, 2020, 34(6):1689-1693.
[36] 中国老年医学学会心电与心功能分会, 中国心衰中心联盟专家委员会, 中华医学会《中华全科医师杂志》编辑委员会. 心力衰竭早期筛查与一级预防中国专家共识(2024年)[J]. 中华全科医师杂志, 2024, 23(1):7-18.
  Chinese Geriatric Society Electrocardiology and Cardiac Function Branch, China Heart Failure Center Alliance Expert Committee, Chinese Medical Association, Chinese Journal of General Practice editorial Committee. Chinese expert consensus on early screening and primary prevention of heart failure (2024)[J]. Chin J Gen Pract, 2024, 23(1):7-18.
[37] 中华医学会老年医学分会心血管疾病学组, 《老年慢性心力衰竭诊治中国专家共识》编写组. 老年人慢性心力衰竭诊治中国专家共识(2021)[J]. 中华老年医学杂志, 2021, 40(5):550-561.
  Cardiovascular Diseases Group, Geriatric Branch of Chinese Medical Association, writing group of Chinese Expert Consensus on Diagnosis and Treatment of Chronic Heart Failure in the Elderly. Chinese experts consensus on the diagnosis and treatment of chronic heart failure in the elderly[J]. Chin J Geriatr, 2021, 40(5):550-561.
[38] MADRY K, ANNA JACHALSKA, PAWEL SZWEDYK, et al. Higher prevalence of chronic kidney disease in myelodysplastic syndromes patients compared to age- adjusted general population - results from the polish adult leukemia group (PALG) registry[J]. Blood, 2023, 142 (Supplement 1):3230.
[39] 中华医学会老年医学分会肾病学组, 国家老年疾病临床医学研究中心. 老年慢性肾脏病诊治的中国专家共识(2018)[J]. 中华老年病研究电子杂志, 2018, 5(3):1-8.
  Nephrology Group of Geriatrics Branch of Chinese Medical Association, National Clinical Research Center for Geriatric Disease. Expert consensus report on the diagnosis and treatment of chronic kidney disease in the Chinese elderly[J]. Chin J Geriatr Res, 2018, 5(3):1-8.
[40] 中华医学会血液学分会血栓与止血学组. 原发免疫性血小板减少症合并血栓/栓塞诊断与防治中国专家共识(2023年版)[J]. 中华血液学杂志, 2023, 44(1):6-11.
  Thrombus and hemostasis Group, Hematology Society, Chinese Medical Association. Chinese expert consensus on the diagnosis and treatment of thromboembolism in patients with immune thrombocytopenia (2023)[J]. Chin J Hematol, 2023, 44(1):6-11.
[41] BRETT J, HENSHALL C, DAWSON P, et al. Examining the levels of psychological support available to patients with haematological cancer in England: a mixed methods study[J]. BMJ Open, 2023, 13(2):e060106.
[42] SWASH B, HULBERT-WILLIAMS N, BRAMWELL R. Unmet psychosocial needs in haematological cancer: a systematic review[J]. Support Care Cancer, 2014, 22(4):1131-1141.
[43] CHEN Q, CHEN K, WANG S, et al. Prognostic value of the controlling nutritional status score in patients with myelodysplastic syndromes[J]. Front Nutr, 2022, 9:902704.
[44] 中华医学会肠外肠内营养学分会. 中国成人患者肠外肠内营养临床应用指南(2023版)[J]. 中华医学杂志, 2023, 103(13):946-974.
  Chinese Society of Parenteral and Enteral Nutrition CSPEN. Guideline for clinical application of parenteral and enteral nutrition in adults patients in China (2023 edition)[J]. Zhonghua Yi Xue Za Zhi, 2023, 103(13):946-974.
[45] PLATZBECKER U, FENAUX P, ADèS L, et al. Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials[J]. Blood, 2019, 133(10):1020-1030.
[46] ZEIDAN A M, PLATZBECKER U, BEWERSDORF J P, et al. Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes[J]. Blood, 2023, 141(17):2047-2061.
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