Leucemia promielocítica aguda. Estado del arte
DOI:
https://doi.org/10.17533//udea.iatreia.76Palabras clave:
leucemia promielocítica aguda, tretinoina, trióxido de arsénicoResumen
La leucemia promielocítica aguda (LPA) es un subtipo de leucemia mieloide aguda (LMA) que se origina por una traslocación balanceada entre los cromosomas 15 y 17, involucra al gen que codifica para el receptor alfa del ácido retinoico (RARA) en el cromosoma 17 y el de la leucemia promielocítica (PML) en el cromosoma 15, lo que da origen a la traslocación t(15;17) PML/RARA. Dicho reordenamiento origina la proteína de fusión PML/RAR alfa, que bloquea la diferenciación de las células madre mieloides en el estadio de promielocito. La LPA afecta con mayor frecuencia a adultos jóvenes y conlleva un alto riesgo de mortalidad temprana, en especial por el desarrollo de una coagulopatía grave, que sin tratamiento es definitivamente fatal. El diagnóstico temprano, el tratamiento de soporte y la introducción de fármacos que promueven la diferenciación terminal de los promielocitos patológicos como la tretinoina, también conocida como ácido todo transretinoico (ATRA) o trióxido de arsénico (ATO), ha hecho que en la actualidad esta sea una enfermedad curable con altas tasas de remisión completa.
Descargas
Citas
(1.) Ryan M. Acute Promyelocytic Leukemia: A Summary. J Adv Pract Oncol. 2018;9(2):178-87. DOI 10.6004/jadpro. 2018.9.2.4.
(2) Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia. N Engl J Med. 2013;369(2):111-21. DOI 10.1056/NEJMoa1300874.
(3) Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. DOI 10.1182/blood-2016-03-643544.
(4) Yamamoto JF, Goodman MT. Patterns of leukemia incidence in the United States by subtype and demographic characteristics, 1997–2002. Cancer Causes Control. 2008;19(4):379-90. DOI 10.1007/s10552-007-9097-2.
(5) Douer D, Preston-Martin S, Chang E, Nichols PW, Watkins KJ, Levine AM. High frequency of acute promyelocytic leukemia among Latinos with acute myeloid leukemia. Blood.1996;87(1):308-13.
(6.) Dinmohamed AG, Visser O. Incidence of acute promyelocytic leukemia across Europe: results of RARECAREnet-a population-based study. Stem Cell Investig. 2019;6:37. DOI 10.21037/sci.2019.10.03.
(7) Matasar MJ, Ritchie EK, Consedine N, Magai C, Neugut AI. Incidence rates of acute promyelocytic leukemia among Hispanics, blacks, Asians, and non-Hispanic whites in the United States: Eur J Cancer Prev. 2006;15(4):367-70. DOI 10.1097/00008469-200608000-00011.
(8) Beaumont M, Sanz M, Carli PM, Maloisel F, Thomas X, Detourmignies L, et al. Therapy-related acute promyelocytic leukemia. J Clin Oncol. 2003;21(11):2123-37. DOI 10.1200/JCO.2003.09.072.
(9) Martínez O. Epidemiología de la leucemia promielocítica aguda en el adulto. Acta Médica Colomb. 2004;29(3):108-11.
(10) Cuenta de Alto Costo. Situación del cáncer en la población adulta atendida en el SGSSS de Colombia. 2019 [internet]. [Consultado 2020 ene 12]. Dispobble en: https://n9.cl/cjvx
(11) Lucena-Araujo AR, Kim HT, Jacomo RH, Melo RA, Bittencourt R, Pasquini R, et al. Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: An International Consortium on Acute Promyelocytic Leukemia study. Ann Hematol. 2014;93(12):2001-10. DOI 10.1007/s00277-014-2142-9.
(12) Rego EM, Jácomo RH. Epidemiology and treatment of acute promyelocytic leukemia in Latin America. Mediterr J Hematol Infect Dis. 2011;3(1):e2011049. DOI 10.4084/mjhid.2011.049.
(13) Mantha S, Tallman MS, Soff GA. What’s new in the pathogenesis of the coagulopathy in acute promyelocytic leukemia? Curr Opin Hematol. 2016;23(2):121-6. DOI 10.1097/MOH.0000000000000221.
(14) David S, Mathews V. Mechanisms and management of coagulopathy in acute promyelocytic leukemia. Thromb Res. 2018;164 Suppl 1:S82-S88. DOI 10.1016/j.thromres.2018.01.041.
(15) De Stefano V, Sorà F, Rossi E, Chiusolo P, Laurenti L, Fianchi L, et al. The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost. 2005;3(9):1985-92. DOI 10.1111/j.1538-7836.2005.01467.x.
(16) Choudhry A, DeLoughery TG. Bleeding and thrombosis in acute promyelocytic leukemia. Am J Hematol. 2012;87(6):596-603. DOI 10.1002/ajh.23158.
(17) Chang H, Kuo M-C, Shih L-Y, Wu J-H, Lin T-L, Dunn P, et al. Acute Promyelocytic Leukemia-Associated Thrombosis. Acta Haematol. 2013;130(1):1-6. DOI 10.1159/000345833.
(18) Montesinos P, Sanz MA. The differentiation syndrome in patients with acute promyelocytic leukemia: experience of the pethema group and review of the literature. Mediterr J Hematol Infect Dis. 2011;3(1):e2011059. DOI 10.4084/mjhid.2011.059.
(19) Stahl M, Tallman MS. Differentiation syndrome in acute promyelocytic leukaemia. Br J Haematol. 2019;187(2):157-62. DOI 10.1111/bjh.16151.
(20) Sanz MA, Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. Blood. 2014;123(18):2777-82. DOI 10.1182/blood-2013-10-512640.
(21) Grignani F, Ferrucci PF, Testa U, Talamo G, Fagioli M, Alcalay M, et al. The acute promyelocytic leukemia-
specific PML-RAR alpha fusion protein inhibits differentiation and promotes survival of myeloid precursor cells. Cell. 1993;74(3):423-31. DOI 10.1016/0092-8674(93)80044-F.
(22) Testa U, Grignani F, Samoggia P, Zanetti C, Riccioni R, Lo Coco F, et al. The PML/RARalpha fusion protein inhibits tumor necrosis factor-alpha-induced apoptosis in U937 cells and acute promyelocytic leukemia blasts. J Clin Invest. 1998;101(10):2278-89. DOI 10.1172/JCI1332.
(23) Lavau C, Dejean A. The t(15;17) translocation in acute promyelocytic leukemia. Leukemia. 1994;8(10):1615-21.
(24) Guidez F, Huang W, Tong JH, Dubois C, Balitrand N, Waxman S, et al. Poor response to all-trans retinoic acid therapy in a t(11;17) PLZF/RAR alpha patient. Leukemia. 1994;8(2):312-7.
(25) Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ. The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood. 1996;87(3):882-6. DOI 10.1182/blood.V87.3.882.bloodjournal873882.
(26) Grignani F, Fagioli M, Alcalay M, Longo L, Pandolfi PP, Donti E, et al. Acute promyelocytic leukemia: from genetics to treatment. Blood. 1994;83(1):10-25. DOI 10.1182/blood.V83.1.10.10.
(27) Wells RA, Hummel JL, De Koven A, Zipursky A, Kirby M, Dubé I, et al. A new variant translocation in acute promyelocytic leukaemia: molecular characterization and clinical correlation. Leukemia. 1996;10(4):735-40.
(28) Kluk MJ, Abo RP, Brown RD, Kuo FC, Dal Cin P, Pozdnyakova O, et al. Myeloid neoplasm demonstrating a STAT5B-RARA rearrangement and genetic alterations associated with all- trans retinoic acid resistance identified by a custom next-generation sequencing assay. Mol Case Stud. 2015;1(1):a000307. DOI 10.1101/mcs.a000307.
(29) Peterson JF, He RR, Nayer H, Cuevo RS, Smadbeck JB, Vasmatzis G, et al. Characterization of a rarelyreported STAT5B/RARA gene fusion in a young adult with newly diagnosed acute promyelocytic leukemia with resistance to ATRA therapy. Cancer Genet. 2019;237:51-4. DOI 10.1016/j.cancergen.2019.06.007.
(30) Ichikawa S, Ichikawa S, Ishikawa I, Takahashi T, Fujiwara T, Harigae H. Successful treatment of acute promyelocytic leukemia with a t(X;17) (p11.4;q21) and BCOR-RARA fusion gene. Cancer Genet. 2015;208(4):162-3. DOI 10.1016/j.cancergen.2015.01.008.
(31) Yamamoto Y, Tsuzuki S, Tsuzuki M, Handa K, Inaguma Y, Emi N. BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17) (p11;q12) variant of acute promyelocytic leukemia. Blood. 2010;116(20):4274-83. DOI 10.1182/blood-2010-01-264432.
(32) Zhu HH, Yang MC, Wang F, Lou YJ, Jin J, Li K, et al. Identification of a novel NUP98-RARA fusion transcript as the 14th variant of acute promyelocytic leukemia. Am J Hematol. 2020;95(7):E184-E186. DOI 10.1002/ajh.25807.
(33) Picharski GL, Andrade DP, Fabro ALMR, Lenzi L, Tonin FS, Ribeiro RC, et al. The Impact of Flt3 Gene Mutations in Acute Promyelocytic Leukemia: A Meta-Analysis. Cancers. 2019;11(9):1311. DOI 10.3390/cancers11091311.
(34) Breccia M, Loglisci G, Loglisci MG, Ricci R, Diverio D, Latagliata R, et al. FLT3-ITD confers poor prognosis in patients with acute promyelocytic leukemia treated with AIDA protocols: long-term follow-up analysis. Haematologica. 2013;98(12):e161-3. DOI 0.3324/haematol.2013.095380.
(35) Tripon F, Crauciuc GA, Boglis A, Moldovan V, Sandor-Keri J, Benedek IJ, et al. Co-occurrence of PML-RARA gene fusion, chromosome 8 trisomy, and FLT3 ITD mutation in a young female patient with de novo acute myeloid leukemia and early death: A CARE case report. Medicine (Baltimore). 2020;99(14):e19730. DOI 10.1097/MD.0000000000019730.
(36) Rasekh EO, Elsayed GM, Madney Y, El Gammal MM. Prognostic Significance of bcr-1 and bcr-3 Isoforms of PML-RARA and FLT3-ITD in Patients With Acute Promyelocytic Leukemia. Clin Lymphoma Myeloma Leuk. 2020;20(3):156-67. DOI 10.1016/j.clml.2019.08.006.
(37) Poiré X, Moser BK, Gallagher RE, Laumann K, Bloomfield CD, Powell BL, et al. Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype. Leuk Lymphoma. 2014;55(7):1523-32. DOI 10.3109/10428194.2013.842985.
(38) Asou N, Adachi K, Tamura J, Kanamaru A, Kageyama S, Hiraoka A, et al. Analysis of prognostic factors in newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Japan Adult Leukemia Study Group. J Clin Oncol. 1998;16(1):78-85. DOI 10.1200/JCO.1998.16.1.78.
(39) Sanz MA, Fenaux P, Tallman MS, Estey EH, Löwenberg B, Naoe T, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European Leukemia-Net. Blood. 2019;133(15):1630-43. DOI 10.1182/blood-2019-01-894980.
(40) Sainty D, Liso V, Cantù-Rajnoldi A, Head D, Mozziconacci MJ, Arnoulet C, et al. A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements. Blood. 2000;96(4):1287-96.
(41) Ma S, Yang L-H, Luedke C, Ingersoll K, Wang E. “Faggot” neutrophils in acute promyelocytic leukaemia with ongoing tretinoin therapy. Br J Haematol. 2018;183(2):169. DOI 10.1111/bjh.15445.
(42) Adams J, Nassiri M. Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations. Arch Pathol Lab Med. 2015;139(10):1308-13. DOI 10.5858/arpa.2013-0345-RS.
(43) Montesinos P, Rayón C, Vellenga E, Brunet S, González J, González M, et al. Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with alltrans retinoic acid and anthracycline-based regimens. Blood. 2011;117(6):1799-805. DOI 10.1182/blood-2010-04-277434.
(44) Hiorns LR, Swansbury GJ, Mehta J, Min T, Dainton MG, Treleaven J, et al. Additional chromosome abnormalities confer worse prognosis in acute promyelocytic leukaemia. Br J Haematol. 1997;96(2):314-21. DOI 10.1046/j.1365-2141.1997.d01-2037.x.
(45) Tallman MS. Acute Myeloid Leukemia (Version 3.2020) [internet]. [Cited 2020 Aug 20]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf
(46) Sanz MA, Montesinos P, Kim HT, et al. All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted treatment of acute promyelocytic leukaemia: a matched-pair analysis of the PETHEMA LPA-2005 and IC-APL studies. Ann Hematol. 2015;94:1347–56. DOI 10.1007/s00277-015-2393-0.
(47) Coutre S. Classification and risk stratification for acute promyelocytic leukemia. Clin Lymphoma Myeloma Leuk. 2010;10 Suppl 3:S127-S129. DOI 10.3816/CLML.2010.s.024.
(48) Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, et al. Improved Outcomes with Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial. J Clin Oncol. 2017;35(6):605-612. DOI 10.1200/JCO.2016.67.1982.
(49) Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M et al. Long-term results of all-trans retinoic acid and arsenic trioxide in nonhigh-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial. Leukemia. 2020;34(3):914-8. DOI 10.1038/s41375-019-0589-3.
(50) Min GJ, Cho BS, Park SS, Park S, Jeon YW, Yahng SA, et al. Safety and efficacy of arsenic trioxide and alltrans retinoic acid therapy in acute promyelocytic leukemia patients with a high risk for early death. Ann Hematol. 2020;99(5):973-82. DOI 10.1007/s00277-020-04010-9.
(51) Nauffal M, Werner L, Ni J, Stone RM, DeAngelo DJ, McDonnell AM. Rate of differentiation syndrome in patients based on timing of initial all-trans retinoic acid administration. Leuk Res Rep. 2019;12:100189. DOI 10.1016/j.lrr.2019.100189.
(52) Montesinos P, Bergua JM, Vellenga E, Rayón C, Parody R, de la Serna J, et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors. Blood. 2009;113(4):775-83. DOI 10.1182/blood-2008-07-168617.
(53) Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003;21(24):4642-9. DOI 10.1200/JCO.2003.04.036.
(54) Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, et al. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015;16(13):1295-305. DOI 10.1016/S1470-2045(15)00193-X.
(55) Raffoux E, Rousselot P, Poupon J, Daniel M-T, Cassinat B, Delarue R, et al. Combined Treatment With Arsenic Trioxide and All-Trans-Retinoic Acid in Patients With Relapsed Acute Promyelocytic Leukemia. J Clin Oncol.2003;21(12):2326-34. DOI 10.1200/JCO.2003.01.149.
(56) Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E, et al. United States Multicenter Study of Arsenic Trioxide in Relapsed Acute Promyelocytic Leukemia. J Clin Oncol. 2001;19(18):3852-60. DOI 10.1200/JCO.2001.19.18.3852.
(57) Aribi A, Kantarjian HM, Estey EH, Koller CA, Thomas DA, Kornblau SM, et al. Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia. Cancer. 2007;109(7):1355-9. DOI 10.1002/cncr.22524.
(58) Ganzel C, Mathews V, Alimoghaddam K, Ghavamzadeh A, Kuk D, Devlin S, et al. Autologous transplant remains the preferred therapy for relapsed APL in CR2. Bone Marrow Transplant. 2016;51(9):1180-3. DOI 10.1038/bmt.2016.96.
(59) Sanz MA, Labopin M, Gorin N-C, de la Rubia J, Arcese W, et al. Hematopoietic stem cell transplantation for adults with acute promyelocytic leukemia in the ATRA era: a survey of the European Cooperative Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2007;39(8):461-9. DOI 10.1038/sj.bmt.1705620.
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2020 Universidad de Antioquia
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-CompartirIgual 4.0.
Los artículos publicados en la revista están disponibles para ser utilizados bajo la licencia Creative Commons, específicamente son de Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional.
Los trabajos enviados deben ser inéditos y suministrados exclusivamente a la Revista; se exige al autor que envía sus contribuciones presentar los formatos: presentación de artículo y responsabilidad de autoría completamente diligenciados.
