Síndrome mielodisplásico

Los SMD ocurren principalmente en adultos mayores; la edad media en el momento del diagnóstico es de 70 a 75 años.[9]Sekeres MA, Taylor J. Diagnosis and treatment of myelodysplastic syndromes: a review. JAMA. 2022 Sep 6;328(9):872-80. http://www.ncbi.nlm.nih.gov/pubmed/36066514?tool=bestpractice.com [10]Roman E, Smith A, Appleton S, et al. Myeloid malignancies in the real-world: occurrence, progression and survival in the UK's population-based Haematological Malignancy Research Network 2004-15. Cancer Epidemiol. 2016 Jun;42:186-98. https://www.sciencedirect.com/science/article/pii/S1877782116300364 http://www.ncbi.nlm.nih.gov/pubmed/27090942?tool=bestpractice.com

Los SMD pueden ocurrir a cualquier edad y deben considerarse en pacientes más jóvenes con exposición previa a quimioterapia o radioterapia, o que tienen un trastorno congénito.

Los fármacos alquilantes (p. ej., clorambucilo, ciclofosfamida, melfalán), inhibidores de la topoisomerasa (p. ej., etopósido, tenipósido), antraciclinas (p. ej., doxorrubicina, daunorrubicina) y agentes de platino (p. ej., cisplatino, carboplatino) se asocian con un mayor riesgo de SMD.[35]Morton LM, Dores GM, Schonfeld SJ, et al. Association of chemotherapy for solid tumors with development of therapy-related myelodysplastic syndrome or acute myeloid leukemia in the modern era. JAMA Oncol. 2019 Mar;5(3):318-25. https://www.doi.org/10.1001/jamaoncol.2018.5625 http://www.ncbi.nlm.nih.gov/pubmed/30570657?tool=bestpractice.com [36]Sill H, Olipitz W, Zebisch A, et al. Therapy-related myeloid neoplasms: pathobiology and clinical characteristics. Br J Pharmacol. 2011 Feb;162(4):792-805. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2010.01100.x http://www.ncbi.nlm.nih.gov/pubmed/21039422?tool=bestpractice.com ​​[37]Kaplan H, Malmgren J, De Roos AJ. Risk of myelodysplastic syndrome and acute myeloid leukemia post radiation treatment for breast cancer: a population-based study. Breast Cancer Res Treat. 2013 Feb;137(3):863-7. http://www.ncbi.nlm.nih.gov/pubmed/23274844?tool=bestpractice.com

La radioterapia se asocia con un mayor riesgo de SMD.[37]Kaplan H, Malmgren J, De Roos AJ. Risk of myelodysplastic syndrome and acute myeloid leukemia post radiation treatment for breast cancer: a population-based study. Breast Cancer Res Treat. 2013 Feb;137(3):863-7. http://www.ncbi.nlm.nih.gov/pubmed/23274844?tool=bestpractice.com La radioterapia combinada con quimioterapia aumenta el riesgo en comparación con la radioterapia sola.[38]Kaplan HG, Malmgren JA, Atwood MK. Increased incidence of myelodysplastic syndrome and acute myeloid leukemia following breast cancer treatment with radiation alone or combined with chemotherapy: a registry cohort analysis 1990-2005. BMC Cancer. 2011 Jun 21;11:260. https://www.doi.org/10.1186/1471-2407-11-260 http://www.ncbi.nlm.nih.gov/pubmed/21693006?tool=bestpractice.com [39]Leone G, Pagano L, Ben-Yehuda D, et al. Therapy-related leukemia and myelodysplasia: susceptibility and incidence. Haematologica. 2007 Oct;92(10):1389-98. https://www.doi.org/10.3324/haematol.11034 http://www.ncbi.nlm.nih.gov/pubmed/17768113?tool=bestpractice.com

Probablemente esté relacionado con el daño del ADN causado por agentes quimioterapéuticos (p. ej., regímenes de acondicionamiento) antes del trasplante autólogo de células madre hematopoyéticas.[40]Stone RM, Neuberg D, Soiffer R, et al. Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma. J Clin Oncol. 1994 Dec;12(12):2535-42. http://www.ncbi.nlm.nih.gov/pubmed/7989927?tool=bestpractice.com

Los SMD en niños y adultos más jóvenes a menudo se asocian con trastornos congénitos.[18]Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 2017 Jan;17(1):5-19. http://www.ncbi.nlm.nih.gov/pubmed/27834397?tool=bestpractice.com

El riesgo de SMD aumenta en personas con síndromes de insuficiencia medular hereditarios (p. ej., anemia de Fanconi, anemia de Diamond-Blackfan, síndrome de Shwachman-Diamond, disqueratosis congénita, neutropenia congénita grave [síndrome de Kostmann]), síndrome de Down (trisomía 21), ataxia telangiectasia , xeroderma pigmentoso, síndrome de Bloom, defecto del gen glutatión transferasa theta 1 (GSTT1) y síndrome de Li-Fraumeni.[15]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: myelodysplastic syndromes [internet publication]. https://www.nccn.org/guidelines/category_1 [16]Fenaux P, Haase D, Santini V, et al; ESMO Guidelines Committee. Myelodysplastic syndromes: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021 Feb;32(2):142-56. https://www.annalsofoncology.org/article/S0923-7534(20)43129-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/33221366?tool=bestpractice.com [18]Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 2017 Jan;17(1):5-19. http://www.ncbi.nlm.nih.gov/pubmed/27834397?tool=bestpractice.com [26]Oetjen KA, Levoska MA, Tamura D, et al. Predisposition to hematologic malignancies in patients with xeroderma pigmentosum. Haematologica. 2020 Apr;105(4):e144-6. https://www.doi.org/10.3324/haematol.2019.223370 http://www.ncbi.nlm.nih.gov/pubmed/31439674?tool=bestpractice.com [27]Aktas D, Koc A, Boduroglu K, et al. Myelodysplastic syndrome associated with monosomy 7 in a child with Bloom syndrome. Cancer Genet Cytogenet. 2000 Jan;116(1):44-6. http://www.ncbi.nlm.nih.gov/pubmed/10616531?tool=bestpractice.com [28]Sutton JF, Stacey M, Kearns WG, et al. Increased risk for aplastic anemia and myelodysplastic syndrome in individuals lacking glutathione S-transferase genes. Pediatr Blood Cancer. 2004 Feb;42(2):122-6. https://www.doi.org/10.1002/pbc.10479 http://www.ncbi.nlm.nih.gov/pubmed/14752874?tool=bestpractice.com [29]Chen H, Sandler DP, Taylor JA, et al. Increased risk for myelodysplastic syndromes in individuals with glutathione transferase theta 1 (GSTT1) gene defect. Lancet. 1996 Feb 3;347(8997):295-7. https://www.doi.org/10.1016/s0140-6736(96)90468-7 http://www.ncbi.nlm.nih.gov/pubmed/8569364?tool=bestpractice.com [30]Dutzmann CM, Spix C, Popp I, et al. Cancer in children with Fanconi anemia and ataxia-telangiectasia - a nationwide register-based cohort study in Germany. J Clin Oncol. 2022 Jan;40(1):32-9. https://www.doi.org/10.1200/JCO.21.01495 http://www.ncbi.nlm.nih.gov/pubmed/34597127?tool=bestpractice.com ​

Un mutágeno conocido.[32]Tong H, Hu C, Yin X, et al. A meta-analysis of the relationship between cigarette smoking and incidence of myelodysplastic syndromes. PLoS One. 2013;8(6):e67537. https://www.doi.org/10.1371/journal.pone.0067537 http://www.ncbi.nlm.nih.gov/pubmed/23805315?tool=bestpractice.com

Los datos observacionales sugieren un mayor riesgo de desarrollar un SMD tras la exposición laboral al benceno.[44]Linet MS, Gilbert ES, Vermeulen R, et al; Chinese Center for Disease Control and Prevention - US National Cancer Institute Benzene Study Group. Benzene exposure response and risk of myeloid neoplasms in Chinese workers: a multicenter case-cohort study. J Natl Cancer Inst. 2019 May 1;111(5):465-74. https://academic.oup.com/jnci/article/111/5/465/5232202 http://www.ncbi.nlm.nih.gov/pubmed/30520970?tool=bestpractice.com [45]Yarosh R, Roesler MA, Murray T, et al. Risk factors for de novo and therapy-related myelodysplastic syndromes (MDS). Cancer Causes Control. 2021 Mar;32(3):241-50. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878335 http://www.ncbi.nlm.nih.gov/pubmed/33392905?tool=bestpractice.com Los posibles mecanismos incluyen la inducción de apoptosis, la alteración del microambiente de la médula ósea y la inducción de desregulación inmunológica.[46]West RR, Stafford DA, Farrow A, et al. Occupational and environmental exposures and myelodysplasia: a case-control study. Leuk Res. 1995 Feb;19(2):127-39. http://www.ncbi.nlm.nih.gov/pubmed/7869741?tool=bestpractice.com

Se puede transformar en SMD.[18]Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 2017 Jan;17(1):5-19. http://www.ncbi.nlm.nih.gov/pubmed/27834397?tool=bestpractice.com [31]Sun L, Babushok DV. Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood. 2020 Jul 2;136(1):36-49. https://www.doi.org/10.1182/blood.2019000940 http://www.ncbi.nlm.nih.gov/pubmed/32430502?tool=bestpractice.com ​

Puede surgir un clon de SMD.[18]Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 2017 Jan;17(1):5-19. http://www.ncbi.nlm.nih.gov/pubmed/27834397?tool=bestpractice.com [31]Sun L, Babushok DV. Secondary myelodysplastic syndrome and leukemia in acquired aplastic anemia and paroxysmal nocturnal hemoglobinuria. Blood. 2020 Jul 2;136(1):36-49. https://www.doi.org/10.1182/blood.2019000940 http://www.ncbi.nlm.nih.gov/pubmed/32430502?tool=bestpractice.com ​