Palabras clave
Leucemia mieloide aguda recaída o refractaria, Tratamiento de rescate, Trasplante de células progenitoras hematopoyéticas, Nuevas estrategias
Cómo citar
Foncuberta, M., & Cranco, S. (2019). Tratamiento de la leucemia mieloide agudarecaída y/o refractaria. Revista Hematología, 21(2), 166–176. Recuperado a partir de https://revistahematologia.com.ar/index.php/Revista/article/view/150
Resumen
La leucemia mieloide aguda comprende un grupo de enfermedades heterogéneas con características fenotípicas y moleculares distintivas. La quimioterapia de inducción es capaz de reducir la carga tumoral a un nivel suficiente para alcanzar los criterios de remisión completa en un porcentaje significativo de casos. Sin embargo, un número no despreciable de pacientes no logran la remisión o recaen, situación de pésimo pronóstico. Los desafíos en el tratamiento de esta población incluyen la evaluación precisa del pronóstico de la enfermedad a través de los estudios genéticos y moleculares, estado funcional del paciente para evaluar la capacidad de tolerar las terapias de rescate, la elección del esquema de tratamiento con mayor probabilidad de éxito y la identificación precisa de quiénes son adecuados para un trasplante de células progenitoras hematopoyéticas. Los médicos tratantes deben considerar todas las estrategias actuales disponibles, que incluyen quimioterapia citotóxica intensiva, drogas dirigidas a nuevos blancos moleculares, tratamiento de baja intensidad y el soporte paliativo. Dado que no existe un estándar de tratamiento en este escenario, la recomendación a nivel mundial es ingresar al paciente en un ensayo clínico, situación no disponible para nosotros en la mayoría de los casos.
Citas
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2. Walter RB, Othus M, Burnett AK y col. Re-sistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOC and MD Anderson Cancer Center. Leu-kemia. 2014;29:312-320.
3. Bose P, Vachhani P, Cortes J. Treatment of Re-lapsed/Refractory Acute Myeloid Leukemia. Curr Treat Options in Oncol. 2017;18:17.
4. Dinardo C, Ravandi F. How Do We Treat Pa-tients with Realpsed/Refractory AML? Oncol-ogy Times. 2015; 37:14-15.
5. Ley TJ, Miller C, Ding L y col. Genomic and Epigenomic Landscapes of Adult De NovoAcute Myeloid Leukemia. N Engl J Med.2013;368:2059-2074.
6. Meggendorfer M, Alpermann T, Perglerová K y col. Genetic Patterns of Relapsed AML Dif-fer Significantly from First Manifestation and Are Dependent on Cytogenetic Risk Groups at Diagnosis: Results in 175 Patients with Paired Samples. Blood. 2014;124:1029.
7. Ferguson P, Craddock C. Allogenic Transplan-tation in Primary Refractory AML. Bone Mar-row Transplantation. 2017:1-2.
8. Döhner H, Estey E, Grimwade D y col. Di-agnosis and Management of AML in Adults: 2017 ELN recommendations from an interna-tional expert panel. Blood. 2017;129:424-447.
9. Gyurkocza B, Lazarus HM, Giralt S. Allogenic Hematopoietic Cell Transplantation in Patients with AML Not Achieving Remission: poten-tially curative therapy. Bone Marrow Trans-plantation. 2017:1-8.
10. Breems DA, Van Putten WL, Löwenberg B. Prognostic Index for Adult Patients with Acute Myeloid Leukemia in First Relapse. J Clin On-col. 2005;23:1969-78.
11. Todisco E, Ciceri F, Rambaldi A y col. Factors Predicting Outcome after Allogenic Transplant in Refractory Acute Myeloid Leukemia: a ret-rospective analysis of Gruppo Italiano Trapi-anto di Midollo Osseo (GITMO). Bone Mar-row Transplantation. 2017:1-7.
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13. Fey MF, Busque C. Acute Myeloblastic Leu-kaemias in Adult Patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:138-143
14. Forman S, Rowe J. The Myth of the Second Remission of Acute Lekemia in the Adult. Blood. 2013;121:1077-1082.
15. Itzykson R, Thépot S, Berthon C y col. Azac-itidine for the Treatment of Relapsed and Re-fractory AML in Older Patients. Leuk Res.2015;39:124-130.
16. Thol F, Schlenk R, Heuser M. How I Treat Refractory and Early Relapsed Acute Myeloid Leukemia. Blood. 2015;126:319-327.
17. Mangan J, Luger S. Salvage Therapy for Re-lapsed or Refractory Acute Myeloid Leukemia. Ther Adv Hematol. 2011;2:73-82.
18. Herzig RH, Lazarus HM, Wolff SN y col. High-dose Cytosine Arabinoside Therapy with and without Anthracycline Antibiotics for Remis-sion Reinduction of Acute Nonlymphoblastic Leukemia. J Clin Oncol. 1985;3:992-997.
19. Anders B, Veltri L, Kanate A y col. Outcomes of Six-Dose High-Dose Cytarabine as a Sal-vage Regimen for Patients with Realpsed/Re-fractory Acute Myeloid Leukemia. Advances in Hematology. 2017;27:1-4.
20. Milligan DW, Wheatley K, Littlewood T y col. Fludarabine and Cytosine are Less Effective than Standard ADE Chemotherapy in High-Risk Acute Myeloid Leukemia, and Addition of G-CSF and ATRA are not beneficial: Results of the MRC AML-HR randomized trial. Blood.2006;107:4614-4622.
21. Wierzbowska A, Robak T, Pluta A y col. Cladribine combined with High Doses of Arab-inoside Cytosine, Mitoxantrone, and G-CSF (CLAG-M) is a Highly Effective Salvage Reg-imen in Patients with Refractory and Relapsed Acute Myeloid Leukemia of Poor Risk: A final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008;80:115-126.
22. Halpern AB, Estey EH, Othus M y col. Mi-toxantrone, Etoposide, and Cytarabine (MEC) following Epigenetic Priming with Decitabine in Adults with Relapsed/Refractory Acute My-eloid Leukemia (AML) or High-Risk Myelo-dysplastic Syndrome (MDS): A phase 1/2 study. Leukemia. 2017 May 30 [Epub ahead of print].
23. Becker PS, Kantarjian HM, Appelbaum FR y col. Retrospective comparison of Clofarabine versus Fludarabine in combination with High-Dose Cytarabine with or without Granulocyte colony-stimulating Factor as Salvage Thera-pies for Acute Myeloid Leukemia. Haemato-logica.2013;98:114-118.
24. Sarkozy C, Gardin C, Gachard N y col. Out-come of Older Patients with Acute Myeloid Leukemia in First Relapse. Am J Hematol.2013;88:758-764.
25. Ivanoff S, Gruson B, Chantepie SP y col. 5-Azacytidine Treatment for Relapsed or Refractory Acute Myeloid Leukemia af-ter Intensive Chemotherapy. Am J Hematol.2013;88:601-605.
26. Ritchie EK, Feldman EJ, Roboz GJ. Decit-abine in Patients with Newly Diagnosed and Relapsed Acute Myeloid Leukemia. Leuk Lym-phoma. 2013;54:2003-2007.
27. Ravandi F, Roboz G, Kantajian H y col. Du-rable Overall Survival Benefit in Patients ≥ 60 Years with Relapsed or Refractory AML Treat-ed with Vosaroxin/Cytarabine Vs Placebo/Cy-tarabine: Updated Results from the Valor Trial. ASH 2016, San Diego, Oral abstract 903.
28. Cortes J, Goldberg S, Feldman E y col. Phase II, Multicenter, Randomized Trial of CPX-351 (cytarabine:Daunorubicin) Liposome Injection versus Intensive Salvage Therapy in Adults with First Relapse AML. Cancer. 2015;121:234-242.
29. Pilorge S, Rigaudeau S, Rabian F y col. Frac-tionated Gemtuzumab ozogamicin and Stan-dard Dose Cytarabine Produced Prolonged Second Remissions in Patients Over the Age of 55 Years with Acute Myeloid Leukemia in Late First Relapse. Am J Hematol. 2014;89:399-403.
30. Walter R, Buckley S, Pagel J y col. Significance of Minimal Residual Disease Before Myeloab-lative Allogeneic Hematopoietic Cell Trans-plantation for AML in First and Second Com-plete Remission. Blood. 2013;122:1813-1821.
31. Duval M, Klein J, He W, y col. Hematopoietic Stem-cell Transplantation for Acute Leukemia in Relapse or Primary Induction Failure. J Clin Oncol. 2010;28:3730-3738.
32. Ferguson P, Hills R, Grech A y col. An Opera-tional Definition of Primary Refractory Acute Myeloid Leukemia allowing Early identifica-tion of Patients who may benefit from Alloge-neic Stem Cell Transplantation. Haematologi-ca. 2016; 101: 1351-1358.
33. Raiola A, Dominietto A, Di Grazia C y col. Unmanipulated Haploidentical Transplants compared with Other Alternative Donors and Matched Sibling Grafts. Biol Blood Marrow Transplant. 2014;20:1573-1579.
34. Sebert M, Porcher R, Robin M y col. Equiv-alent Outcomes Using Reduced Intensity or Conventional Myeloablative Conditioning Transplantation for Patients Aged 35 Years and Over with AML. Bone Marrow Transplant.2015;50:74-81.
35. Schmid C, Schleuning M, Schwerdtfeger R y col. Long-term Survival in Refractory Acute Myeloid Leukemia after Sequential Treatment with Chemotherapy and Reduced-intensity Conditioning for Allogeneic Stem Cell Trans-plantation. Blood. 2006;108:1092-1099.
36. Mohty M, Malard F, Blaise D y col. Sequen-tial Regimen of Clofarabine, Cytosine arabino-side and Reduced Intensity Transplantation for Primary Refractory Acute Myeloid Leukemia. Haematologica. 2016;102:184-191.
37. Bejanyan N, Oran B, Shanley R y col. Clini-cal Outcomes of AML Patients Relapsing after Matched-related Donor and Umbilical Cord Blood Transplantation. Bone Marrow Trans-plant. 2014;49:1029-1035.
38. De Lima M, Giralt S, Thall P y col. Mainte-nance Therapy with Low-dose Azacitidine after Allogeneic Hematopoietic Stem Cell Transplantation for Recurrent Acute Myeloge-nous Leukemia or Myelodysplastic Syndrome: a Dose and Schedule finding Study. Cancer.2010;116: 5420-5431.
39. Craddock C, Jilani N, Siddique S y col. Toler-ability and Clinical Activity of Post-transplan-tation Azacitidine in Patients Allografted for Acute Myeloid Leukemia treated on the RI-CAZA Trial. Biol Blood Marrow Transplant.2016;22: 385-390.
2. Walter RB, Othus M, Burnett AK y col. Re-sistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOC and MD Anderson Cancer Center. Leu-kemia. 2014;29:312-320.
3. Bose P, Vachhani P, Cortes J. Treatment of Re-lapsed/Refractory Acute Myeloid Leukemia. Curr Treat Options in Oncol. 2017;18:17.
4. Dinardo C, Ravandi F. How Do We Treat Pa-tients with Realpsed/Refractory AML? Oncol-ogy Times. 2015; 37:14-15.
5. Ley TJ, Miller C, Ding L y col. Genomic and Epigenomic Landscapes of Adult De NovoAcute Myeloid Leukemia. N Engl J Med.2013;368:2059-2074.
6. Meggendorfer M, Alpermann T, Perglerová K y col. Genetic Patterns of Relapsed AML Dif-fer Significantly from First Manifestation and Are Dependent on Cytogenetic Risk Groups at Diagnosis: Results in 175 Patients with Paired Samples. Blood. 2014;124:1029.
7. Ferguson P, Craddock C. Allogenic Transplan-tation in Primary Refractory AML. Bone Mar-row Transplantation. 2017:1-2.
8. Döhner H, Estey E, Grimwade D y col. Di-agnosis and Management of AML in Adults: 2017 ELN recommendations from an interna-tional expert panel. Blood. 2017;129:424-447.
9. Gyurkocza B, Lazarus HM, Giralt S. Allogenic Hematopoietic Cell Transplantation in Patients with AML Not Achieving Remission: poten-tially curative therapy. Bone Marrow Trans-plantation. 2017:1-8.
10. Breems DA, Van Putten WL, Löwenberg B. Prognostic Index for Adult Patients with Acute Myeloid Leukemia in First Relapse. J Clin On-col. 2005;23:1969-78.
11. Todisco E, Ciceri F, Rambaldi A y col. Factors Predicting Outcome after Allogenic Transplant in Refractory Acute Myeloid Leukemia: a ret-rospective analysis of Gruppo Italiano Trapi-anto di Midollo Osseo (GITMO). Bone Mar-row Transplantation. 2017:1-7.
12. NCCN. Acute Myeloid Leukemia NCCN Guidelines. NCCN Clin Parct Guidelines On-col. 2017; 3.2017:1.108.
13. Fey MF, Busque C. Acute Myeloblastic Leu-kaemias in Adult Patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:138-143
14. Forman S, Rowe J. The Myth of the Second Remission of Acute Lekemia in the Adult. Blood. 2013;121:1077-1082.
15. Itzykson R, Thépot S, Berthon C y col. Azac-itidine for the Treatment of Relapsed and Re-fractory AML in Older Patients. Leuk Res.2015;39:124-130.
16. Thol F, Schlenk R, Heuser M. How I Treat Refractory and Early Relapsed Acute Myeloid Leukemia. Blood. 2015;126:319-327.
17. Mangan J, Luger S. Salvage Therapy for Re-lapsed or Refractory Acute Myeloid Leukemia. Ther Adv Hematol. 2011;2:73-82.
18. Herzig RH, Lazarus HM, Wolff SN y col. High-dose Cytosine Arabinoside Therapy with and without Anthracycline Antibiotics for Remis-sion Reinduction of Acute Nonlymphoblastic Leukemia. J Clin Oncol. 1985;3:992-997.
19. Anders B, Veltri L, Kanate A y col. Outcomes of Six-Dose High-Dose Cytarabine as a Sal-vage Regimen for Patients with Realpsed/Re-fractory Acute Myeloid Leukemia. Advances in Hematology. 2017;27:1-4.
20. Milligan DW, Wheatley K, Littlewood T y col. Fludarabine and Cytosine are Less Effective than Standard ADE Chemotherapy in High-Risk Acute Myeloid Leukemia, and Addition of G-CSF and ATRA are not beneficial: Results of the MRC AML-HR randomized trial. Blood.2006;107:4614-4622.
21. Wierzbowska A, Robak T, Pluta A y col. Cladribine combined with High Doses of Arab-inoside Cytosine, Mitoxantrone, and G-CSF (CLAG-M) is a Highly Effective Salvage Reg-imen in Patients with Refractory and Relapsed Acute Myeloid Leukemia of Poor Risk: A final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008;80:115-126.
22. Halpern AB, Estey EH, Othus M y col. Mi-toxantrone, Etoposide, and Cytarabine (MEC) following Epigenetic Priming with Decitabine in Adults with Relapsed/Refractory Acute My-eloid Leukemia (AML) or High-Risk Myelo-dysplastic Syndrome (MDS): A phase 1/2 study. Leukemia. 2017 May 30 [Epub ahead of print].
23. Becker PS, Kantarjian HM, Appelbaum FR y col. Retrospective comparison of Clofarabine versus Fludarabine in combination with High-Dose Cytarabine with or without Granulocyte colony-stimulating Factor as Salvage Thera-pies for Acute Myeloid Leukemia. Haemato-logica.2013;98:114-118.
24. Sarkozy C, Gardin C, Gachard N y col. Out-come of Older Patients with Acute Myeloid Leukemia in First Relapse. Am J Hematol.2013;88:758-764.
25. Ivanoff S, Gruson B, Chantepie SP y col. 5-Azacytidine Treatment for Relapsed or Refractory Acute Myeloid Leukemia af-ter Intensive Chemotherapy. Am J Hematol.2013;88:601-605.
26. Ritchie EK, Feldman EJ, Roboz GJ. Decit-abine in Patients with Newly Diagnosed and Relapsed Acute Myeloid Leukemia. Leuk Lym-phoma. 2013;54:2003-2007.
27. Ravandi F, Roboz G, Kantajian H y col. Du-rable Overall Survival Benefit in Patients ≥ 60 Years with Relapsed or Refractory AML Treat-ed with Vosaroxin/Cytarabine Vs Placebo/Cy-tarabine: Updated Results from the Valor Trial. ASH 2016, San Diego, Oral abstract 903.
28. Cortes J, Goldberg S, Feldman E y col. Phase II, Multicenter, Randomized Trial of CPX-351 (cytarabine:Daunorubicin) Liposome Injection versus Intensive Salvage Therapy in Adults with First Relapse AML. Cancer. 2015;121:234-242.
29. Pilorge S, Rigaudeau S, Rabian F y col. Frac-tionated Gemtuzumab ozogamicin and Stan-dard Dose Cytarabine Produced Prolonged Second Remissions in Patients Over the Age of 55 Years with Acute Myeloid Leukemia in Late First Relapse. Am J Hematol. 2014;89:399-403.
30. Walter R, Buckley S, Pagel J y col. Significance of Minimal Residual Disease Before Myeloab-lative Allogeneic Hematopoietic Cell Trans-plantation for AML in First and Second Com-plete Remission. Blood. 2013;122:1813-1821.
31. Duval M, Klein J, He W, y col. Hematopoietic Stem-cell Transplantation for Acute Leukemia in Relapse or Primary Induction Failure. J Clin Oncol. 2010;28:3730-3738.
32. Ferguson P, Hills R, Grech A y col. An Opera-tional Definition of Primary Refractory Acute Myeloid Leukemia allowing Early identifica-tion of Patients who may benefit from Alloge-neic Stem Cell Transplantation. Haematologi-ca. 2016; 101: 1351-1358.
33. Raiola A, Dominietto A, Di Grazia C y col. Unmanipulated Haploidentical Transplants compared with Other Alternative Donors and Matched Sibling Grafts. Biol Blood Marrow Transplant. 2014;20:1573-1579.
34. Sebert M, Porcher R, Robin M y col. Equiv-alent Outcomes Using Reduced Intensity or Conventional Myeloablative Conditioning Transplantation for Patients Aged 35 Years and Over with AML. Bone Marrow Transplant.2015;50:74-81.
35. Schmid C, Schleuning M, Schwerdtfeger R y col. Long-term Survival in Refractory Acute Myeloid Leukemia after Sequential Treatment with Chemotherapy and Reduced-intensity Conditioning for Allogeneic Stem Cell Trans-plantation. Blood. 2006;108:1092-1099.
36. Mohty M, Malard F, Blaise D y col. Sequen-tial Regimen of Clofarabine, Cytosine arabino-side and Reduced Intensity Transplantation for Primary Refractory Acute Myeloid Leukemia. Haematologica. 2016;102:184-191.
37. Bejanyan N, Oran B, Shanley R y col. Clini-cal Outcomes of AML Patients Relapsing after Matched-related Donor and Umbilical Cord Blood Transplantation. Bone Marrow Trans-plant. 2014;49:1029-1035.
38. De Lima M, Giralt S, Thall P y col. Mainte-nance Therapy with Low-dose Azacitidine after Allogeneic Hematopoietic Stem Cell Transplantation for Recurrent Acute Myeloge-nous Leukemia or Myelodysplastic Syndrome: a Dose and Schedule finding Study. Cancer.2010;116: 5420-5431.
39. Craddock C, Jilani N, Siddique S y col. Toler-ability and Clinical Activity of Post-transplan-tation Azacitidine in Patients Allografted for Acute Myeloid Leukemia treated on the RI-CAZA Trial. Biol Blood Marrow Transplant.2016;22: 385-390.
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