Guía de manejo para el tratamiento de la Leucemia linfoide aguda hospital de San José, Bogotá D.C.
Treatment guidelines for acute lym phoblastic leukemia at hospital de San Jose, Bogota DC.
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Figueroa Camacho, J. L., Solano, M. H., & Villamizar Gómez, L. (2010). Guía de manejo para el tratamiento de la Leucemia linfoide aguda hospital de San José, Bogotá D.C. Revista Repertorio De Medicina Y Cirugía, 19(3), 174–186. https://doi.org/10.31260/RepertMedCir.v19.n3.2010.596
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Los esquemas para el tratamiento de leucemia linfoblástica aguda, muestran tasas de remisión completa entre 70 y 90%, pero con pobres resultados a largo plazo y supervivencia libre de enfermedad a cinco años de 30 a 40%. Ante los múltiples protocolos a nivel mundial, las diferentes respuestas clínicas, la controversia en las opciones terapéuticas y la dificultad de adaptar las estrategias de tratamiento en nuestro país, se justifica la realización de una guía para nuestra institución. Se realizó una búsqueda de literatura sobre el tratamiento de LLA en adultos. Se excluyeron los de LLA en pediatría y LLA de precursores T. Se encontraron 335 artículos y se seleccionaron 48 que cumplieron los criterios de inclusión. Objetivo: establecer estrategias terapéuticas en adultos con LLA basadas en la evidencia disponible y adaptándolas a los recursos institucionales. Materiales y métodos: la revisión ampliada se basó en la evaluación de estudios secundarios como guías de práctica clínica, metaanálisis, revisiones sistemáticas publicadas entre enero 2005 y febrero 2009, o bien se recurrió a ensayos clínicos. Las bases de datos analizadas incluyeron PubMed a través de Medline, Clinical Evidence, la colaboración Cochrane, así como treinta y cuatro entidades compiladoras. Conclusiones: 1) Para adultos con LLA las series más grandes concluyen que el tratamiento de inducción debe incluir corticoides, antracíclicos, vincristina y L asparaginasa, con profilaxis del sistema nervioso central. 2) Los adolescentes y adultos jóvenes deben recibir protocolos pediátricos pero no hay evidencia suficiente para aceptar uno estándar. 3) El imatinib está indicado para todos los pacientes con LLA Ph+ con dosis entre 400 y 800 mg/día desde la inducción hasta el final del tratamiento. El beneficio es mayor cuando se incorpora desde la inducción y se administra en forma concurrente, con la quimioterapia, más que de forma secuencial. 4) Los esquemas consistentes con quimioterapia de alta intensidad asociada con imatinib y consolidación con trasplante alogénico en la primera remisión completa, han mostrado los mejores resultados a largo plazo y constituyen la terapia estándar. 5) Se recomienda monitorizar la enfermedad mínima residual en LLA Ph+ luego de trasplante alogénico por ser factor predictor de recaída. 6) No existen estudios comparativos aleatorios controlados que evalúen el impacto del imatinib en presencia de enfermedad mínima residual y es difícil llevarlos a cabo por la baja incidencia. La investigación de Wassmann y col. sugiere un beneficio a largo término en quienes logran respuesta molecular completa temprana con imatinib.
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Referencias
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26. Ribera J,OriolA, Bethencourt C et al. Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatrnent for adult patients with high-risk acule lymphoblastic leukemia. Results of the PETHEMAALL-93 trial. Haematologica.2005; 90:1346-56.
27. Orsi C, Bartolozzi B, MessoriA, BosiA.Event-freesurvival and cost-effectiveness in adult acule lymphoblastic leukaemia in first remission treated with allogeneic transplantation. Bone Marrow Transplant. 2007;40 (7): 643-9.
28. Stock W, La M, Sanford B et al.Adolescents and Yong adults with acute Jymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric oncology cooperative group treatment regimens: a comparison of Children's Cancer Group (CCG) and Cancer and Leukemia Group B (CALGB) studies. Blood. 2008;112:1646-54.
29. Boissel N, Auclerc MF, Lhéritier V, et al. Should adolescents with acule lyrnphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003;21:774-80.
30. de Bont JM, Holt B, Dekker AW, et al. Sigrúficant difference in outcome for adolescents with acule lyrnphoblastic leucemia treated on pediatric vs adult protocols in the Netherlands. Leukemia. 2004;18:2032-5.
31. Rarnanujachar R, Richards S, Hann I, et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK nacional paediatric(ALL97) and adult (UKALLXIJ/E2993) triaIs. Pediatr Blood Cancer.2007;48:254-61.
32. Hallboi:ik H, Gustafsson G, Smedmyr B, et al. Treatment outcome in young adults and children >1O years of age with acule lymphoblastic leukemia in Sweden: acompariciónbetween a pediatricprotocol and an adult protocol. Cancer. 2006;107:1551-61.
33. Ribera JM, Albert O, Miguel-Angel S, et al.Comparison of the results of the treatment of adolescents and young adults with standard-risk acule lymphoblastic leukemia with the Programa Espanol de Trata miento en Hematologia pediatricbased protocol ALL-96.J Clin Oncol. 2008;26:1843-9.
34. Faderl S, Kantarjian HM,Talpaz M, Estrov Z.Significance of cytogenetic abnormalities inadult acule lymphoblasticleukemia. Blood. 1998;9 I:3995- 4019.
35. Larson RA. Management of acule lymphoblastic leukemia in older patients. Semin Hematol. 2006;43:126-33.
36. Faderl S, Kantarjian H, Thomas DA eal. Outcome of Philadelphia chromosome-positive adult acule lymphoblastic leukemia.LeukLymphoma. 2000;36:263-73.
37. Walker l.Toe use of Imatinib Mesylate (gleevec) inpatients whith Philadelphia chromosome-positive adult acute lymphoblastic leucemia. Ontario: Cancer Care Ontario; 2008. Sep 29. Report No.: IO.
38. Thomas DA, Kantarjian HM, Cortes JE, Ravandi F, Faderl S, Jones D. Outcome after frontline therapy with the hyper CVAD and imatinib mesylate regirnen for adults with de novo or minimally treated Philadelphia (Ph) positive acule lymphoblastic leukemia (ALL). In: 2008ASCOAnnual Mee ting; 2008 May 30-Jun 3; Chicago, Illinois: ASCO.
39. Ribera JM, Oriol A, Gonzalez M, Vidriales M-B, Xicoy B, Grau J, et al. Treatment of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) with concurren! chemotherapy and imatinib mesylate. In: Abstracts of the American Society of Hernatology 46th Annual Meeting; 2004 Dec. 4-7; California: ASH.
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42. Delannoy A, Delabesse E, Lhéritier V, Castaigne S, Rigal-Huguet F, Raffoux E, et al. lmatinib and ethylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALLAFR09 study. Leukemia. 2006;20(9):1526-32.
43. Wassmann B, Pfeifer H, Scheuring UJ, BinckebanckA, Gokbuget N, Atta J, et al. Altemating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukernia (Ph+ ALL). Blood. 2006;108(5): 1469-77.
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2. Pui CH, Evans WE. Treatment ofacute lymphoblastic leukemia. N Engl J Med. 2006 Jan 12; 354(2): 166-78.
3. Gokbuget N, Hoelzer D. Treatment ofadult acule lymphoblastic leukemia. HematologyAm Soc Hematol Educ Program. 2006;133-41.
4. Hoeltzer D, GoKbuget N. Treatment ofadult acule lymphoblastic leukemia. Hematology. 2006;1: 162-92.
5. Enciso L, Rodríguez M, et al. Consensocolombiano sobre el tratamiento de la leucemia linfoblástica aguda en adultos. Rev Colomb Cancero! 2006;10(1):7-35.
6. Rowe J. How I treat acute Lymphoblastic Leukemia in Adults. Blood 2007;1!0(7): 2268-75
7. Scottish Intercollegiale Guideline Network. SIGN 50: a guideline developers' handbook. Edinburgh: SIGN; 2008.
8. TheAGREE Collaboration.Appraisal ofGuidelines for Research & Evaluation (AGREE) lnstrument. London: AGREE; 2003.
9. Hoelzer D, Gokbugel N. Treatment ofadull acule lymphoblastic leukemia. Semin Hematol. 2009;46(1):64-75.
10. Rowe J, Goldstone A. How I treat acute lymphocytic leukemia in adults. Blood. 2007;110 (7): 2268-75.
11. Takeuchi J, Kyo T, Naito K, et al. Induction therapyby frequent admirústration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acule lymphoblastic leukemia:the JALSG ALL93 study. Leukemia. 2002;16 (7):1259-66.
12. Rowe JM, Buck G, BumettAK, et al. Induction therapy for adults with acule lymphoblastic leukemia: results of more than 1500 patients from the international ALL tria!: MRC UKALL XII/ECOG E2993. Blood. 2005;106(12):3760-7.
13. Larson R, Dodge R, Linker C, et al. A randomized controlled tria! of filgrastim during remission induction and consolidation chemotherapy for adults with acule lymphoblastic leukemia: CALGB study 9111. Blood. 1998;92(5):1556-64.
14. Kantarjian H, Thomas D, O'Brien S, et al.Long-term followup results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper CVAD), a dose-intensive regimen, in adult acule lymphocytic leukemia. Cancer. 2004;1O1:2788-801.
15. Gokbuget N, Arnold R, Buechner T, et al. Intensification of induction and consolidation improves only subgroups of adult ALL: Analysis of 1200 patients in GMALL study 05/93 [abstrae!].Blood.2001;98: 802.
16. Thomas X, Boiron JM, Huguet F, et al.Outcome of treatrnent in adults with acule lymphoblastic leukemia: analysis of the LALA-94 tria!. J Clin Oncol. 2004; 22:4075-86.
17. Mancirú M. An integrated molecular-cytogenetic classification is highly predictive of outcomein adult acute lymphoblastic leukemia (ALL): analysis of 395 cases enrolled in the GIMEMA 0496 trial. Blood.2001; 98:3492a.
18. Kantarjian H, O'Brien S, Smith TL, et al.Results of treatment with hyper CVAD, a dose-intensive regirnen, in adult acule lymphocytic leukemia. J Clin Oncol. 2000;18:547-61.
19. Combariza J, Casas C.Adult acule lymphoid leukemia survival in patients receiving treatrnent with HyperCVAD at the Instituto Nacional de Cancero logía (Colombia), January 2001 to June 2005. Rev Colomb Cancerol. 2007;11(2): 92-100.
20. Yanada M, Matsuo K. Allogenichematopoietic steam cell transplantation as part of postremission therapy improves survival for adult patients with high risk acute Lymphoblastic Leukemia. A metaanalisis. Cancer. 2006;106(12).
21. Sebban C, Lepage E, Vemant JP etal.Allogeneic bone marrow transplantation inadult acule lymphoblastic leucemia in first completeremission: a comparative study. French Group ofTherapy of Adult Acute Lymphoblastic Leukemia. J Clin Oncol. 1994;12(2580):2587.
22. Dombret H, Gabert J, Boiron JM et al. Outcome of treatment in adults with Philadelphia chromosome-positive acule lymphoblastic leukemia-results of the prospective multicenter LALA-94 trial. Blood. 2002; 100: 2357-66.
23. Thomas X, Boiron J, Huguet F et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004; 22:4075-86.
24. Hunault M, Harousseau JL, Delain M, et al. Better out come of adult acute lyrnphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial.Blood. 2004;104:3028-37.
25. Labar B, Suciu S, Zittoun R, et al. Allogeneic stem cell transplantación in acute lymphoblastic leukemia and non-Hodgkin's lymphoma for patients or 50 years old in first complete remission: results of the EORTC ALL-3 trial. Haematologica. 2004;89:809-17.
26. Ribera J,OriolA, Bethencourt C et al. Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatrnent for adult patients with high-risk acule lymphoblastic leukemia. Results of the PETHEMAALL-93 trial. Haematologica.2005; 90:1346-56.
27. Orsi C, Bartolozzi B, MessoriA, BosiA.Event-freesurvival and cost-effectiveness in adult acule lymphoblastic leukaemia in first remission treated with allogeneic transplantation. Bone Marrow Transplant. 2007;40 (7): 643-9.
28. Stock W, La M, Sanford B et al.Adolescents and Yong adults with acute Jymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric oncology cooperative group treatment regimens: a comparison of Children's Cancer Group (CCG) and Cancer and Leukemia Group B (CALGB) studies. Blood. 2008;112:1646-54.
29. Boissel N, Auclerc MF, Lhéritier V, et al. Should adolescents with acule lyrnphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003;21:774-80.
30. de Bont JM, Holt B, Dekker AW, et al. Sigrúficant difference in outcome for adolescents with acule lyrnphoblastic leucemia treated on pediatric vs adult protocols in the Netherlands. Leukemia. 2004;18:2032-5.
31. Rarnanujachar R, Richards S, Hann I, et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK nacional paediatric(ALL97) and adult (UKALLXIJ/E2993) triaIs. Pediatr Blood Cancer.2007;48:254-61.
32. Hallboi:ik H, Gustafsson G, Smedmyr B, et al. Treatment outcome in young adults and children >1O years of age with acule lymphoblastic leukemia in Sweden: acompariciónbetween a pediatricprotocol and an adult protocol. Cancer. 2006;107:1551-61.
33. Ribera JM, Albert O, Miguel-Angel S, et al.Comparison of the results of the treatment of adolescents and young adults with standard-risk acule lymphoblastic leukemia with the Programa Espanol de Trata miento en Hematologia pediatricbased protocol ALL-96.J Clin Oncol. 2008;26:1843-9.
34. Faderl S, Kantarjian HM,Talpaz M, Estrov Z.Significance of cytogenetic abnormalities inadult acule lymphoblasticleukemia. Blood. 1998;9 I:3995- 4019.
35. Larson RA. Management of acule lymphoblastic leukemia in older patients. Semin Hematol. 2006;43:126-33.
36. Faderl S, Kantarjian H, Thomas DA eal. Outcome of Philadelphia chromosome-positive adult acule lymphoblastic leukemia.LeukLymphoma. 2000;36:263-73.
37. Walker l.Toe use of Imatinib Mesylate (gleevec) inpatients whith Philadelphia chromosome-positive adult acute lymphoblastic leucemia. Ontario: Cancer Care Ontario; 2008. Sep 29. Report No.: IO.
38. Thomas DA, Kantarjian HM, Cortes JE, Ravandi F, Faderl S, Jones D. Outcome after frontline therapy with the hyper CVAD and imatinib mesylate regirnen for adults with de novo or minimally treated Philadelphia (Ph) positive acule lymphoblastic leukemia (ALL). In: 2008ASCOAnnual Mee ting; 2008 May 30-Jun 3; Chicago, Illinois: ASCO.
39. Ribera JM, Oriol A, Gonzalez M, Vidriales M-B, Xicoy B, Grau J, et al. Treatment of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) with concurren! chemotherapy and imatinib mesylate. In: Abstracts of the American Society of Hernatology 46th Annual Meeting; 2004 Dec. 4-7; California: ASH.
40. Fielding AK, Richards SM, Lazarus HM, Litzow MR, Luger SM, Marks DI, et al.Does imatinib change the outcome in Philadelphia chromosome positive acule lymphoblastic leukemia in adults? Data from the UKALLXII/ECOG2993 study.In: Abstracts of the American Society of Hematology 49th Annual Meeting; 2007 Dec. 8-11; Atlanta, Giorgia: ASH.
41. de Labarthe A, Rousselot P, Huget-Rigal F, Delabesse E, Witz F, Maury S, et al. Jmatinib combined with induction or consolidationchemotherapy in
lymphoblastic leukemia: results of the GRAAPH- 2003 study. Blood. 2007;109(4):1408-13.
42. Delannoy A, Delabesse E, Lhéritier V, Castaigne S, Rigal-Huguet F, Raffoux E, et al. lmatinib and ethylprednisolone alternated with chemotherapy improve the outcome of elderly patients with Philadelphia-positive acute lymphoblastic leukemia: results of the GRAALLAFR09 study. Leukemia. 2006;20(9):1526-32.
43. Wassmann B, Pfeifer H, Scheuring UJ, BinckebanckA, Gokbuget N, Atta J, et al. Altemating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukernia (Ph+ ALL). Blood. 2006;108(5): 1469-77.
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